Ignite Creation Date:
2025-12-24 @ 11:16 PM
Ignite Modification Date:
2025-12-25 @ 8:53 PM
Study NCT ID:
NCT00033956
Status:
SUSPENDED
Last Update Posted:
2005-06-24
First Post:
2002-04-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Evaluation of M40403 for the Prevention of Dose Limiting Toxicities of High Dose IL-2
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008545', 'term': 'Melanoma'}, {'id': 'D002292', 'term': 'Carcinoma, Renal Cell'}, {'id': 'D007022', 'term': 'Hypotension'}], 'ancestors': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C121876', 'term': 'imisopasem manganese'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'count': 48}}, 'statusModule': {'overallStatus': 'SUSPENDED', 'startDateStruct': {'date': '2001-12'}, 'statusVerifiedDate': '2002-05', 'lastUpdateSubmitDate': '2005-06-23', 'studyFirstSubmitDate': '2002-04-17', 'studyFirstSubmitQcDate': '2002-04-17', 'lastUpdatePostDateStruct': {'date': '2005-06-24', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2002-04-18', 'type': 'ESTIMATED'}}, 'conditionsModule': {'keywords': ['Metastatic Melanoma', 'Renal Cell Carcinoma', 'IL-2', 'Interleukin-2', 'Hypotension'], 'conditions': ['IL-2 Induced Hypotension']}, 'descriptionModule': {'briefSummary': 'The clinical use of IL-2 is currently limited by development of dose-dependent hypotension (systolic blood pressure (SBP) \\< 90 mm Hg). The overall outcome is constant across sites with 20-50% of the patients requiring ICU management because of unresponsive hypotension and hyporeactivity (loss of response to vasoconstrictors). Because of the dose-limiting side effects, the duration of IL-2 dosing is frequently curtailed. Thus, hemodynamic toxicities have limited the usefulness of IL-2 therapy. M40403 has prevented both the hypotension and hyporeactivity associated with IL-2 treatment in preclinical studies. This trial will study the safety and efficacy of M40403 in the prevention or reduction of hypotension in patients receiving IL-2 therapy.', 'detailedDescription': "High-dose interleukin-2 (IL-2) therapy is currently indicated for treatment of metastatic renal cell carcinoma and metastatic malignant melanoma, and has been associated with a 5-15% long-term clinical response. In addition, IL-2 therapy is showing promise in treatment of acute myelogenous leukemia, non-Hodgkin's lymphoma, and breast cancer, and in improving immunologic function in patients with AIDS. However, the major dose-limiting toxicity of IL-2, hypotension, severely limits the usefulness of IL-2 therapy.\n\nBecause of the unresponsive hypotension and loss of response to exogenously administered vasopressors, 20-50% of the patients receiving high dose IL-2 therapy require ICU management. These dose-limiting side effects frequently necessitate curtailing the full period of IL-2 dosing in order to reverse the hypotension and prevent subsequent renal dysfunction. Thus, hemodynamic toxicities have limited the usefulness of IL-2 therapy. A course of IL-2 therapy requires long hospitalization and intense patient monitoring during administration. As a consequence, despite favorable long-term response, few sites offer this treatment.\n\nThe availability of an agent that prevents IL-2-induced hypotension without adversely affecting the therapeutic mechanism of IL-2, would markedly facilitate IL-2 administration and at a minimum, would maximize the number of patients who could receive the full regimen of IL-2. The reduction in IL-2 toxicity may also enable higher doses and/or more frequent dosing of IL-2 to be used, with the potential of higher success of tumor response. Because M40403 may decrease the toxicity of IL-2, co-administration of M40403 may make it possible to broaden the clinical use of IL-2 to conditions where it is not currently indicated.\n\nThe indication to be studied is for use in the prevention or reduction of hypotension associated with interleukin-2 (IL-2) therapy in patients with metastatic melanoma and renal cell carcinoma.\n\nThe study is divided into a sequential dose escalation phase followed by the expansion of the selected dose in a double-blind, placebo-controlled, evaluation phase. Patients with metastatic or inoperable melanoma and renal cell carcinoma will be receiving high dose IL-2 per approved labeling as two 5-day sequences. M40403 will be administered by intravenous infusion over 30 minutes prior to each intravenous administration of high dose IL-2. Sequential panels of patients will receive increasing doses of M40403 along with IL-2 until an active dose is determined and an MTD is reached. Patients will be followed to determine the effects of M40403 on development of markers of IL-2 dose-limiting toxicity including hypotension, tachycardia, index of renal perfusion, cumulative dose of pressor required and cumulative dose of IL-2 administered. Approximately 48 patients will be studied."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patient has given signed informed consent.\n* Patient has documented histologically confirmed malignant melanoma or renal cell carcinoma which is metastatic.\n* Patient is eligible for high dose IV IL-2 therapy.\n* Tumor dimension of at least one lesion is measurable in two dimensions.\n* Patient is at least 18 years of age.\n* Patient is ambulatory with good performance status (ECOG PS 0,1; Karnofsky 100-70%).\n* If the patient is a woman of child bearing potential, patient is not lactating and ahs a negative pregnancy test (beta-HCG test obtained within 72 hours of enrollment) and agrees to use an adequate method of contraception for the duration of the study.\n* Patient has adequate organ function as defined by:\n\n * WBC count \\>3,500 per cubic millimeter; platelet count\\> 100,000 per cubic millimeter;\n * Bilirubin within institutional normal range; creatinine less than or equal to 2.0 mg/dl or creatinine clearance \\> 50 ml/min;\n * No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias or evidence of prior myocardial infarction. A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment. Patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study;\n * Adequate pulmonary reserve. Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment and an FEV1 \\> 2.0 liters or 75% of predicted for height and age is the minimum acceptable criteria for patient entry. PAtients unable to perform PFTs will be excluded from the study.\n* Patient has recovered from all toxic effects of prior therapy.\n* Patient has a life expectancy, in the opinion of the investigator, of at least 4 months.\n\nExclusion Criteria:\n\n* Patient has an organ allograft.\n* Patient has brain metastases. A Brain CT or MRI scan should be performed within 42 days of IL-2 treatment.\n* Patient is know to be HIV antibody positive. HIV testing is not required for enrollment into this study.\n* Patient has evidence of active infection which requires antibiotic therapy.\n* Patient has received systemic corticosteroids in the four weeks prior to the first dose of study drug, or requires or is anticipated to require corticosteroids for intercurrent disease.\n* Patient has received radiotherapy, chemotherapy, or immunotherapy in the four weeks prior to the first dose of study drug, or is scheduled to receive concurrent radiotherapy, chemotherapy, or immunotherapy.\n* Patient has contraindication to treatment with pressor agents.\n* Patient currently receives chronic medication for asthma.\n* Patient has a history of another malignancy other than basal cell skin cancer within 5 years prior to the first dose of study drug.\n* Patient has any significant medical disease other than the malignancy which, in the opinion of the investigator, may interfere with completion of the study.\n* Patient has previously received any IL-2 therapy.\n* Patient has received another investigational medication within 4 weeks prior to M40403 administration or is scheduled to receive an investigational drug other than M40403 during the course of the study.'}, 'identificationModule': {'nctId': 'NCT00033956', 'briefTitle': 'Evaluation of M40403 for the Prevention of Dose Limiting Toxicities of High Dose IL-2', 'organization': {'class': 'INDUSTRY', 'fullName': 'MetaPhore Pharmaceuticals'}, 'officialTitle': 'Phase I/II Open Label Dose Escalation and Double-Blind, Placebo-Controlled Evaluation of M40403, for the Prevention of the Dose Limiting Toxicities of High Dose IV Bolus IL-2 Treatment of Metastatic Melanoma or Renal Cell Carcinoma.', 'orgStudyIdInfo': {'id': 'U10-01-12-002'}}, 'armsInterventionsModule': {'interventions': [{'name': 'M40403', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '60611-2927', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Northwestern University Medical School', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '97213-3635', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Providence Portland Medical Center', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'Huntsman Cancer Institute', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'MetaPhore Pharmaceuticals', 'class': 'INDUSTRY'}}}}