Ignite Creation Date:
2025-12-24 @ 11:50 PM
Ignite Modification Date:
2026-02-28 @ 3:31 AM
Study NCT ID:
NCT01578551
Status:
TERMINATED
Last Update Posted:
2018-12-19
First Post:
2012-04-13
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002289', 'term': 'Carcinoma, Non-Small-Cell Lung'}, {'id': 'D000077192', 'term': 'Adenocarcinoma of Lung'}], 'ancestors': [{'id': 'D002283', 'term': 'Carcinoma, Bronchogenic'}, {'id': 'D001984', 'term': 'Bronchial Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017239', 'term': 'Paclitaxel'}, {'id': 'D016190', 'term': 'Carboplatin'}, {'id': 'D000068258', 'term': 'Bevacizumab'}, {'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D043823', 'term': 'Taxoids'}, {'id': 'D043822', 'term': 'Cyclodecanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D004224', 'term': 'Diterpenes'}, {'id': 'D013729', 'term': 'Terpenes'}, {'id': 'D056831', 'term': 'Coordination Complexes'}, {'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ettinda@Jhmi.edu', 'phone': '410-955-8847', 'title': 'David Ettinger, MD', 'organization': 'Johns Hopkins University'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'up to 1 year', 'eventGroups': [{'id': 'EG000', 'title': 'Arm A', 'description': 'Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.\n\nPaclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nBevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.', 'otherNumAtRisk': 19, 'deathsNumAtRisk': 19, 'otherNumAffected': 19, 'seriousNumAtRisk': 19, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Arm B', 'description': 'Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 6, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'White blood cell count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Neutrophil count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Lymphocyte count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Febrile neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Appendicitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Catheter-related infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hyponatremia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypokalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypophosphatemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hyperglycemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dehydration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Infusion related reaction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Neuropathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Bone pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Thomboembolic event', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Colonic perforation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Progression Free Survival (PFS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A', 'description': 'Metformin 500 mg twice a day, orally with meals. After one week, increase 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.\n\nPaclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.'}, {'id': 'OG001', 'title': 'Arm B', 'description': 'Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.'}], 'classes': [{'categories': [{'measurements': [{'value': '9.6', 'comment': 'The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.', 'groupId': 'OG000', 'lowerLimit': '7.3', 'upperLimit': 'NA'}, {'value': '6.7', 'comment': 'The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.', 'groupId': 'OG001', 'lowerLimit': '4.4', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '1 year', 'description': 'Number of months without evidence of progression after 1 year of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Response to Therapy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A', 'description': 'Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.\n\nPaclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: 15 mg/kg every 21 days,'}, {'id': 'OG001', 'title': 'Arm B', 'description': 'Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.'}], 'classes': [{'categories': [{'measurements': [{'value': '56', 'groupId': 'OG000', 'lowerLimit': '31', 'upperLimit': '78'}, {'value': '33', 'groupId': 'OG001', 'lowerLimit': '6', 'upperLimit': '76'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '2 years', 'description': 'Percentage of participants with complete or partial response to combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Overall Survial', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A', 'description': 'Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.\n\nPaclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: 15 mg/kg every 21 days,'}, {'id': 'OG001', 'title': 'Arm B', 'description': 'Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.'}], 'classes': [{'categories': [{'measurements': [{'value': '15.9', 'comment': 'The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.', 'groupId': 'OG000', 'lowerLimit': '8.4', 'upperLimit': 'NA'}, {'value': '13.9', 'comment': 'The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.', 'groupId': 'OG001', 'lowerLimit': '12.7', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'up to 2 years', 'description': 'Number of months alive after 1 year of the combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Arm A', 'description': 'Metformin dose of 500 mg twice a day After one week, increase dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin tx initiated 1 week before beginning chemotherapy, chemotherapy not delayed for metformin loading.\n\nPaclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nBevacizumab: 15 mg/kg every 21 days, every 21 days until PD'}, {'id': 'FG001', 'title': 'Arm B', 'description': 'Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Arm A', 'description': 'Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.\n\nPaclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.\n\n.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carbop'}, {'id': 'BG001', 'title': 'Arm B', 'description': 'Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy.\n\nCarboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy\n\nBevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '58', 'groupId': 'BG000', 'lowerLimit': '37', 'upperLimit': '74'}, {'value': '64', 'groupId': 'BG001', 'lowerLimit': '55', 'upperLimit': '70'}, {'value': '61', 'groupId': 'BG002', 'lowerLimit': '37', 'upperLimit': '74'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '19', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 25}}, 'statusModule': {'whyStopped': 'Low enrollment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2012-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-12', 'completionDateStruct': {'date': '2017-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-12-16', 'studyFirstSubmitDate': '2012-04-13', 'resultsFirstSubmitDate': '2018-09-18', 'studyFirstSubmitQcDate': '2012-04-13', 'lastUpdatePostDateStruct': {'date': '2018-12-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-12-16', 'studyFirstPostDateStruct': {'date': '2012-04-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-12-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Progression Free Survival (PFS)', 'timeFrame': '1 year', 'description': 'Number of months without evidence of progression after 1 year of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.'}], 'secondaryOutcomes': [{'measure': 'Response to Therapy', 'timeFrame': '2 years', 'description': 'Percentage of participants with complete or partial response to combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1'}, {'measure': 'Overall Survial', 'timeFrame': 'up to 2 years', 'description': 'Number of months alive after 1 year of the combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Carcinoma, Non-Small-Cell Lung', 'Lung adenocarcinoma'], 'conditions': ['Carcinoma, Non-Small-Cell Lung', 'Lung Adenocarcinoma']}, 'referencesModule': {'references': [{'pmid': '29487223', 'type': 'RESULT', 'citation': 'Marrone KA, Zhou X, Forde PM, Purtell M, Brahmer JR, Hann CL, Kelly RJ, Coleman B, Gabrielson E, Rosner GL, Ettinger DS. A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naive Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer. Oncologist. 2018 Jul;23(7):859-865. doi: 10.1634/theoncologist.2017-0465. Epub 2018 Feb 27.'}]}, 'descriptionModule': {'briefSummary': 'To determine the 1 year progression-free survival (PFS) of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.', 'detailedDescription': "Primary Objectives\n\nTo determine the 1 year progression-free survival (PFS) of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.\n\nSecondary Objectives\n\nA. To evaluate the response to therapy and overall survival of the combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.\n\nB. To determine whether LKB1 gene status in tumors is a significant determinant of response when metformin is added to the therapy C. To acquire preliminary data regarding the effects of metformin on uptake of fluorodeoxyglucose in tumor and normal tissues.\n\nTreatment will be administered on an outpatient basis.\n\nInduction Therapy (Step 1, Cycles 1-4)\n\nMetformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.\n\nPaclitaxel 200 mg/m2 IV over 3 hours. For Paclitaxel pre-medication information\n\nCarboplatin AUC = 6 mg/ml IV over 15 - 30 minutes, immediately following paclitaxel infusion\n\nBevacizumab 15 mg/kg IV infusion over 30 - 90 minutes\n\nMetformin will be administered continuously, beginning one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading. The other three drugs (paclitaxel, carboplatin, and bevacizumab) will be administered on day 1 of each 21 day cycle.\n\nMaintenance Therapy\n\nPatients responding to this therapy will be maintained with metformin (1000 mg twice daily) and bevacizumab (15 mg/kg IV over 30-90 minutes on day 1 of each 21-day cycle).\n\nDuration of Therapy\n\nIn the absence of treatment delays due to adverse events, treatment may continue until one of the following criteria applies:\n\n1. Disease progression,\n2. Intercurrent illness that prevents further administration of treatment,\n3. Unacceptable adverse events(s),\n4. Patient decides to withdraw from the study, or\n5. General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '100 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nPatients must have Histologically or cytologically confirmed non-squamous cell, non small cell carcinoma of the lung.\n\nPatient must have measurable stage IV disease (includes M1a, M1b stages or recurrent disease) (according to the 7th edition of the TNM classification system). However, patients with T4NX disease (stage III B) with nodule(s) in ipsilateral lung lobe are not eligible, because such patients were not included in historical controls.\n\nPatients be age \\>18 years.\n\nPatients must have a Life Expectancy of greater than 12 weeks.\n\nPatients must have an ECOG performance status 0 or 1 (Karnofsky \\> 70%; see Appendix A).\n\nPatients must have normal organ and marrow function as defined below, within one week prior to randomization:\n\n* absolute neutrophil count \\>1,500/mcL\n* platelets \\> 100,000/mcL\n* total bilirubin: within normal institutional limits\n* AST(SGOT)/ALT(SGPT) \\< 2.5 X institutional upper limit of normal\n* creatinine ≤ 1.5 X institutional upper limit of normal\n* urine dipstick for proteinuria of \\< less than 1+. If urine dipstick is \\> 1+ then a 24 hour urine for protein must demonstrate \\< 500 mg of protein in 24 hours to allow participation in the study.\n\nWomen of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.\n\nPatients must have an INR \\< 1.5 and a PTT no greater than upper limits of normal within 1 week prior to randomization.\n\nPatients with a history of hypertension must be well-controlled (\\<150sytolic/\\<100diastolic) on a stable regimen of anti-hypertensive therapy.\n\nPatients must have the ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\nPatients with a history of gross hemoptysis (defined as bright red blood of ½ teaspoon or more) will be excluded from this trial.\n\nPatients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.\n\nPatients with a history of thrombotic or hemorrhagic disorders.\n\nPatients receiving chronic daily treatment with aspirin (\\> 325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal)is also not allowed.\n\nPatients receiving therapeutic anticoagulation. Prophylactic anticoagulation of venous access devices is allowed provided Section 3.10 is met. Caution should be taken on treating patients with low dose heparin or low molecular weight heparin for DVT prophylaxis during treatment with bevacizumab as there may be an increased risk of bleeding.\n\nPrior use of chemotherapy.\n\nPatients receiving immunotherapy, hormonal-therapy and or radiotherapy within 2 weeks prior to entering the study. Note: Those who have not recovered from adverse events due to these agents administered will be considered ineligible.\n\nPatients receiving any other investigational agents.\n\nPatients with a serious non-healing wound ulcer, or bone fracture, or major surgical procedure within 21 days prior to starting treatment.\n\nPatients with uncontrolled brain metastasis. Note: Patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.\n\nPatients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin and paclitaxel or other agents used in the study are excluded.\n\nWomen that are pregnant or breastfeeding Note: Pregnant women are excluded from this study because the agents used in this study may be teratogenic to a fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding women are also excluded from this study.\n\nPatients that are HIV-positive on combination antiretroviral therapy due to the potential for lethal infections when treated with marrow-suppressive therapy.'}, 'identificationModule': {'nctId': 'NCT01578551', 'briefTitle': 'Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.', 'organization': {'class': 'OTHER', 'fullName': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins'}, 'officialTitle': 'A Randomized Phase II Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Previously Untreated Advanced/Metastatic Pulmonary Adenocarcinoma', 'orgStudyIdInfo': {'id': 'J1188'}, 'secondaryIdInfos': [{'id': 'NA_00052073', 'type': 'OTHER', 'domain': 'JHM IRB'}, {'id': '2P50CA058184-16', 'link': 'https://reporter.nih.gov/quickSearch/2P50CA058184-16', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Arm A', 'description': 'Paclitaxel, Carboplatin, Bevacizumab, and Metformin. Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.', 'interventionNames': ['Drug: Paclitaxel', 'Drug: Carboplatin', 'Drug: Bevacizumab', 'Drug: Metformin']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Arm B', 'description': 'Paclitaxel, Carboplatin, and Bevacizumab', 'interventionNames': ['Drug: Paclitaxel', 'Drug: Carboplatin', 'Drug: Bevacizumab']}], 'interventions': [{'name': 'Paclitaxel', 'type': 'DRUG', 'otherNames': ['Taxol', 'NSC 673089'], 'description': '200 mg/m² IV over 3 hours, day 1 of each cycle. Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy.', 'armGroupLabels': ['Arm A', 'Arm B']}, {'name': 'Carboplatin', 'type': 'DRUG', 'otherNames': ['platinum diamine', 'Paraplatin'], 'description': 'Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days\n\nPaclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy', 'armGroupLabels': ['Arm A', 'Arm B']}, {'name': 'Bevacizumab', 'type': 'DRUG', 'otherNames': ['NSC 704865', 'RhuMAb VEGF', 'Recombinant Humanized Monoclonal Anti-VEGF Antibody'], 'description': 'All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.', 'armGroupLabels': ['Arm A', 'Arm B']}, {'name': 'Metformin', 'type': 'DRUG', 'otherNames': ['N,N - dimethyl biguanide hydrochloride', 'glucophage'], 'description': '1000 mg twice daily with food.', 'armGroupLabels': ['Arm A']}]}, 'contactsLocationsModule': {'locations': [{'zip': '21224', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins Bayview Medical Center', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '21231', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins University SKCCC', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}], 'overallOfficials': [{'name': 'David Ettinger, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Johns Hopkins SKCCC'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}