Ignite Creation Date:
2025-12-25 @ 3:53 AM
Ignite Modification Date:
2026-03-05 @ 10:33 PM
Study NCT ID:
NCT04177602
Status:
TERMINATED
Last Update Posted:
2023-02-22
First Post:
2019-11-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012004', 'term': 'Rectal Neoplasms'}], 'ancestors': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}, {'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D014271', 'term': 'Trifluridine'}], 'ancestors': [{'id': 'D013936', 'term': 'Thymidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003853', 'term': 'Deoxyribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Seamless phase I/II trial with phase I part for determination of maximum tolerated dose (MTD) of Trifluridine/tipiracil, followed by a randomized phase II trial (randomization ratio 2:1) with an experimental arm with Trifluridine/tipiracil based chemoradiotherapy (CRT) and a standard - calibration arm (internal control) with capecitabine CRT flanked by translational research'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'whyStopped': 'Due to the amended therapy strategies for rectal cancer recently, it was decided not to transfer the study to the phase II part, as superiority over standard chemoradiation and transfer to a new therapy standard are increasingly unlikely.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2019-11-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-02', 'completionDateStruct': {'date': '2022-09-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-02-20', 'studyFirstSubmitDate': '2019-11-20', 'studyFirstSubmitQcDate': '2019-11-22', 'lastUpdatePostDateStruct': {'date': '2023-02-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-11-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-09-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum tolerated dose (MTD)/Phase 1 part', 'timeFrame': '8 weeks', 'description': 'Toxicity'}, {'measure': 'Rate of pathological complete remissions (pCR)/Phase 2 part', 'timeFrame': '3 months', 'description': 'Pathohistological response'}], 'secondaryOutcomes': [{'measure': 'Disease free survival (DFS)', 'timeFrame': '4 years', 'description': 'recurrence and survival'}, {'measure': 'Overall survival (OS)', 'timeFrame': '4 years', 'description': 'Survival'}, {'measure': 'Loco-regional failure', 'timeFrame': '4 years', 'description': 'Loco-regional recurrence'}, {'measure': 'Histopathological R0 resection rate', 'timeFrame': '3 months', 'description': 'Pathohistological response'}, {'measure': 'Tumour regression grades', 'timeFrame': '3 months', 'description': 'Pathohistological response'}, {'measure': 'Pathological down-staging (ypT0-2N0) rate', 'timeFrame': '3 months', 'description': 'Pathohistological response'}, {'measure': 'Neoadjuvant rectal score (NAR)', 'timeFrame': '3 months', 'description': 'Clinical stage and Pathohistological response (\\<8 low, 8-16 intermediate, \\>16 high risk)'}, {'measure': 'Adverse event rate', 'timeFrame': '3 months', 'description': 'Rate of adverse events according to NCI CTC AE v5'}, {'measure': 'Rate of perioperative complications', 'timeFrame': '3 months', 'description': 'Perioperative complications'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['trifluridine tipiracil chemoradiation', 'locally advanced rectal cancer', 'neoadjuvant', 'adenocarcinoma of the rectum'], 'conditions': ['Locally Advanced Rectal Cancer']}, 'referencesModule': {'references': [{'pmid': '39003182', 'type': 'DERIVED', 'citation': 'Thiele B, Stein A, Schultheiss C, Paschold L, Jonas H, Goekkurt E, Russel J, Schuch G, Wierecky J, Sinn M, Tintelnot J, Petersen C, Rothkamm K, Vettorazzi E, Binder M. Trifluridine/Tipiracil Based Chemoradiation in locally Advanced Rectal Cancer: The Phase I/II TARC Trial. Clin Colorectal Cancer. 2025 Mar;24(1):11-17. doi: 10.1016/j.clcc.2024.06.003. Epub 2024 Jun 22.'}, {'pmid': '32891715', 'type': 'DERIVED', 'citation': 'Rothkamm K, Christiansen S, Rieckmann T, Horn M, Frenzel T, Brinker A, Schumacher U, Stein A, Petersen C, Burdak-Rothkamm S. Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays. Cancer Lett. 2020 Nov 28;493:179-188. doi: 10.1016/j.canlet.2020.08.038. Epub 2020 Sep 4.'}]}, 'descriptionModule': {'briefSummary': 'Seamless phase I/II trial with phase I part for determination of maximum tolerated dose (MTD) of Trifluridine/tipiracil, followed by a randomized phase II trial (randomization ratio 2:1) with an experimental arm with Trifluridine/tipiracil based chemoradiotherapy (CRT) and a standard - calibration arm (internal control) with capecitabine CRT flanked by translational research in patients with locally advanced rectal cancer', 'detailedDescription': 'This is a multicenter randomized seamless phase I/II trial with a phase I for determination of maximum tolerated dose (MTD) of Trifluridine/tipiracil, followed by a randomized phase II trial (randomization ratio 2:1) with an experimental arm with Trifluridine/tipiracil in combination with standard radiotherapy and a standard - calibration arm (internal control) with capecitabine CRT flanked by translational research, designed to assess the clinical performance and efficacy of Trifluridine/tipiracil compared to current standard capecitabine chemoradiation in patients with locally advanced rectal cancer.\n\nThe primary clinical objective in phase I is to determine the dosage and feasibility of Trifluridine/tipiracil based chemoradiation and in phase II whether Trifluridine/tipiracil with preoperative chemoradiation improves pathological complete remissions in patients with locally advanced rectal cancer.\n\nThe secondary objectives are to evaluate Trifluridine/tipiracil chemoradiation with respect to disease free survival, overall survival, local regional failure, pathological down-staging (ypT0-2N0) rate, tumour regression grade, histopathological R0 resection rate, neoadjuvant rectal score (NAR), and perioperative complication rate. Safety and toxicity, according to NCI CTC AE v5, quality of life and feasibility of the regimen are further secondary objectives that are to be evaluated.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Male or female patients with histologically proven adenocarcinoma of the rectum (tumour ≤ 12 cm from the anal verge)\n2. Indication for neoadjuvant chemoradiation: clinical tumour stage T3/4 or any node-positive disease (clinical stage according the TNM classification system, based on MRI).\n3. No evidence of metastatic disease (as evidenced by negative CT-scan of the chest and abdomen).\n4. The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemoradiation.\n5. Age ≥ 18 years\n6. WHO/ECOG Performance Status ≤ 2\n7. No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.\n8. No prior radiotherapy to the pelvis, for any reason.\n9. Presence of adequate contraception in fertile patients. Adequate methods of contraception are: intra-uterine device, hormonal contraception, condom use with spermicide. Pregnant or breastfeeding women are excluded from participation.\n10. Adequate bone marrow, hepatic and renal function: Haemoglobin ≥9.0 g/dL (transfusions allowed to achieve or maintain levels), absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, ALAT, ASAT ≤ 2.5 x ULN, Alkaline phosphatase ≤ 2.5 x ULN, Total bilirubin ≤1.5 x ULN, Creatinine clearance \\> 50 mL/min (calculated according to Cockroft and Gault).\n11. Ability to swallow tablets.\n12. Written informed consent and patient's agreement to comply with the study protocol.\n\nExclusion Criteria:\n\n1. Previous (within the last 3 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin.\n2. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.\n3. Known allergy or any other adverse reaction to any of the study drugs or to any related compound.\n4. Known significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease).\n5. Pre-existing condition which would deter chemoradiotherapy or radiotherapy, i.e. fistulas, severe ulcerative colitis (particularly patients currently taking sulphasalazine), Crohn's disease, prior adhesions."}, 'identificationModule': {'nctId': 'NCT04177602', 'briefTitle': 'Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial', 'organization': {'class': 'OTHER', 'fullName': 'Universitätsklinikum Hamburg-Eppendorf'}, 'officialTitle': 'Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial', 'orgStudyIdInfo': {'id': 'TARC-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Trifluridine/tipiracil based radiotherapy', 'description': 'Trifluridine/tipiracil based chemoradiotherapy (CRT)', 'interventionNames': ['Combination Product: Trifluridine/tipiracil chemoradiation']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'standard calibration arm (internal control)', 'description': 'capecitabine based chemoradiotherapy', 'interventionNames': ['Combination Product: Capecitabine based chemoradiation']}], 'interventions': [{'name': 'Trifluridine/tipiracil chemoradiation', 'type': 'COMBINATION_PRODUCT', 'description': 'Trifluridine/tipiracil based chemoradiation', 'armGroupLabels': ['Trifluridine/tipiracil based radiotherapy']}, {'name': 'Capecitabine based chemoradiation', 'type': 'COMBINATION_PRODUCT', 'description': 'Capecitabine based chemoradiation', 'armGroupLabels': ['standard calibration arm (internal control)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '24939', 'city': 'Flensburg', 'state': 'Schleswig-Holstein', 'country': 'Germany', 'facility': 'Malteser Krankenhaus St. Franziskus Hospital', 'geoPoint': {'lat': 54.78805, 'lon': 9.43722}}, {'zip': '23562', 'city': 'Lübeck', 'state': 'Schleswig-Holstein', 'country': 'Germany', 'facility': 'Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt, Kirso, Weber', 'geoPoint': {'lat': 53.86893, 'lon': 10.68729}}, {'zip': '21680', 'city': 'Stade', 'state': 'Schleswig-Holstein', 'country': 'Germany', 'facility': 'Klinik Dr. Hancken / MVZ Onkologie'}, {'city': 'Halle', 'country': 'Germany', 'facility': 'University Medical Center Halle', 'geoPoint': {'lat': 51.48158, 'lon': 11.97947}}, {'zip': '20249', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'Hämatologisch- Onkologische Praxis Eppendorf (HOPE)', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '20251', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'II. Medizinische Klinik und Poliklinik Hubertus Wald Tumorzentrum - UCCH', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '20259', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'Überörtliche Gemeinschaftspraxis für Innere Medizin Schwerpunkt Hämatologie, Onkologie und Palliativmedizin Dres. Verpoort, Wierecky & Zeller', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '22767', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'Hämatologisch- Onkologische Praxis Altona (HOPA)', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}], 'overallOfficials': [{'name': 'Alexander Stein', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Cancer Center Hamburg'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Universitätsklinikum Hamburg-Eppendorf', 'class': 'OTHER'}, 'collaborators': [{'name': 'Clinical Trial Center North (CTC North GmbH & Co. KG)', 'class': 'OTHER'}, {'name': 'Servier Affaires Médicales', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}