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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT05223673
Other study ID # CL3-95026-001
Secondary ID 2021-003151-41
Status Terminated
Phase Phase 3
First received
Last updated
Start date April 21, 2022
Est. completion date June 21, 2023

Study information

Verified date February 2024
Source Servier
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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).


Recruitment information / eligibility

Status Terminated
Enrollment 7
Est. completion date June 21, 2023
Est. primary completion date June 21, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
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.
Drug:
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.
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.

Locations

Country Name City State
Belgium UZA Edegem Edegem
Belgium UZ Leuven Campus Gasthuisberg Leuven
Belgium CHUUCL Namur site Godinne Yvoir
Denmark Rigshospitalet Copenhagen
Denmark Herning Regional Hospital (Regionhospitalet Godstrup) Herning
Denmark Odense Universitetshospital Odense
Finland Docrates cancer center Helsinki
Finland TAYS (Tampere University Hospital) Tampere
Hungary Magyar Honvédség Egészségügyi Központ Onkológiai Osztály Budapest
Hungary Debreceni Egyetem, Klinikai Központ Onkológiai Klinika Debrecen
Hungary Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudomáyi Kar Oktatókórháza Kecskemét
Hungary Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika Szeged
Japan National Cancer Center Hospital East Chiba
United States University of Michigan Oncology Clinic | Rogel Cancer Center Ann Arbor Michigan
United States Cleveland Clinic Cleveland Clinic Lerner College of Medicine Cleveland Ohio

Sponsors (2)

Lead Sponsor Collaborator
Institut de Recherches Internationales Servier ADIR, a Servier Group company

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  Finland,  Hungary,  Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part) DLTs observed during a 28-day period. A DLT is defined as the following: A clinically significant AE graded according to the NCI-CTCAE version 5.0, observed during the initial 28- day treatment period following the first IMP administration. Assessed as unrelated to underlying disease, disease progression, intercurrent illness, or concomitant medications. At least possibly related to the IMPs (futuximab/modotuximab or trifluridine/tipiracil or both) by the investigator and meeting criteria as outlined in the protocol. End of cycle 1 (Each cycle is up to 28 days)
Primary Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part) Time elapsed from date of randomization until the date of death from any cause up to 4 years 9 months
Secondary Overall Survival (Safety Lead-In Part) Time elapsed from the first IMP intake to death up to 24 months
Secondary Overall Survival (In Triple Negative) (Phase III Part) Time elapsed from the date of randomization into the study to disease progression/death up to 4 years 9 months
Secondary Progression Free Survival (Phase III Part) Time elapsed from the date of randomization into the study to disease progression/death up to 4 years 9 months
Secondary Adverse Events (Phase III Part) Incidence, severity, and relationship of treatment emergent adverse event and treatment emergent serious adverse event Through study completion, up to 4 years 9 months
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