Clinical trial
A Randomised, Open-label, Multi-centre, Two-arm Phase 3 Study Comparing Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil to Trifluridine/Tipiracil Single Agent With a Safety Lead-In Part in Participants With KRAS/NRAS and BRAF Wild Type Metastatic Colorectal Cancer Previously Treated With Standard Treatment and Anti-EGFR Therapy
Name
CL3-95026-001
Description
This is a randomized phase III study with a safety lead-in part in patients with KRAS/ NRAS and BRAF Wild Type metastatic colorectal cancer who have previously received treatment with oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF agents and anti-EGFR antibodies. The main objective of the safety lead-in part is to assess safety and tolerability of futuximab/modotuximab in combination with trifluridine/tipiracil. The primary objective of the phase III part is to compare Overall Survival of futuximab/modotuximab in combination with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy in patients with tumours that are KRAS/NRAS and BRAF wild-type (WT).
Trial arms
Trial start
2022-04-21
Estimated PCD
2023-06-21
Trial end
2023-06-21
Status
Terminated
Phase
Early phase I
Treatment
Futuximab/modotuximab
Concentrate for solution for infusion, futuximab/modotuximab will be administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Arms:
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)
Trifluridine/Tipiracil
Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.
Arms:
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)
Trifluridine/Tipiracil
Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.
Arms:
Trifluridine/tipiracil (Phase III part)
Size
7
Primary endpoint
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)
End of cycle 1 (Each cycle is up to 28 days)
Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part)
up to 4 years 9 months
Eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of metastatic colorectal cancer (mCRC), not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumour without RAS (KRAS and NRAS) and BRAF V600E mutations based on Circulating tumour DNA (ctDNA) screening blood test analysis
* Participants with measurable or non-measurable lesion
* Participants must have received at least 2 prior regimens of standard chemotherapy for mCRC and had demonstrated progressive disease or intolerance to their last regimen
* Participants should have received previous treatment with commercially available anti-EGFR mAbs for ≥ 4 months
* Estimated life expectancy ≥ 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate haematological, renal and hepatic function
Exclusion Criteria:
* Pregnancy, possibility of becoming pregnant during the study, breastfeeding woman
* Patients currently receiving or having received anticancer therapies within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part).
* Major surgery within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part) or participants who have not recovered from side effects of the surgery
* Participants with serious/active/uncontrolled infection
* Known clinically significant cardiovascular disease or condition
* Significant gastrointestinal abnormality
* Skin rash of Grade \> 1 from prior anti-EGFR at the time of inclusion (Safety Lead-in part) or randomization (Phase 3 part), or any other skin toxicity precluding participation in the study according to investigator's discretion.
* Treatment with systemic immunosuppressive therapy within 4 weeks prior to inclusion (Safety Lead-in part) or randomization (Phase 3 part)
* Prior radiotherapy if completed less than 4 weeks before the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part)
* Patients with other malignancies
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 7, 'type': 'ACTUAL'}}
Updated at
2024-03-05
1 organization
2 products
1 indication
Organization
Institut de Recherches Internationales ServierProduct
Futuximab/modotuximabIndication
Colorectal CancerProduct
Trifluridine/Tipiracil