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

Metastatic Colorectal Cancer Clinical Trial

— COLSTAR  

Official title:

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

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
• 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
• 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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

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

External Links

•   Find Results on Servier Clinical Trial Data website