Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer

NCT ID: NCT05223673

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-21
• Study Completion Date: 2023-06-21

Brief 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).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)

Group Type: EXPERIMENTAL

Futuximab/modotuximab

Intervention Type: BIOLOGICAL

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.

Trifluridine/Tipiracil

Intervention Type: DRUG

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 (Phase III part)

Group Type: ACTIVE_COMPARATOR

Trifluridine/Tipiracil

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fortunato Ciardiello

Role: PRINCIPAL_INVESTIGATOR

University of Campania Luigi Vanvitelli

Locations

University of Michigan Oncology Clinic | Rogel Cancer Center

Ann Arbor, Michigan, United States

Cleveland Clinic Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, United States

UZA Edegem

Edegem, , Belgium

UZ Leuven Campus Gasthuisberg

Leuven, , Belgium

CHUUCL Namur site Godinne

Yvoir, , Belgium

Rigshospitalet

Copenhagen, , Denmark

Herning Regional Hospital (Regionhospitalet Godstrup)

Herning, , Denmark

Odense Universitetshospital

Odense, , Denmark

Docrates cancer center

Helsinki, , Finland

TAYS (Tampere University Hospital)

Tampere, , Finland

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, , Hungary

National Cancer Center Hospital East

Chiba, , Japan

Countries

United States; Belgium; Denmark; Finland; Hungary; Japan

References

Ciardiello F, Yoshino T, Modest DP, Martin Fernandez L, Roby L, Fougeray R, Lockhart BP, Tabernero J. 436TiP COLSTAR: Randomized, open-label, multicentre, phase III study comparing futuximab/modotuximab plus trifluridine/tipiracil to trifluridine/tipiracil in KRAS/NRAS and BRAF wild type (wt) metastatic colorectal cancer (mCRC) previously treated with both standard and anti-EGFR treatment. Ann Oncol. 2022 Sep;33(Supplement 7):S733-S73. doi: 10.1016/j.annonc.2022.07.574

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study-level clinical trial data

View Document

Related Links

https://clinicaltrials.servier.com/

Find Results on Servier Clinical Trial Data website

Other Identifiers

2021-003151-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL3-95026-001

Identifier Type: -

Identifier Source: org_study_id