NCT05223673

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).

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Apr 2022

Shorter than P25 for phase_3

Geographic Reach
6 countries

15 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 25, 2022

Completed
10 days until next milestone

First Posted

Study publicly available on registry

February 4, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

April 21, 2022

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 21, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 21, 2023

Completed
9 months until next milestone

Results Posted

Study results publicly available

March 5, 2024

Completed
Last Updated

August 20, 2024

Status Verified

July 1, 2024

Enrollment Period

1.2 years

First QC Date

January 25, 2022

Results QC Date

January 16, 2024

Last Update Submit

July 24, 2024

Conditions

Keywords

Futuximab/modotuximabTrifluridine/tipiracilPhase IIISafety Lead-In partS95026Sym004AdultMetastaticColorectalColorectal CancerEGFR

Outcome Measures

Primary Outcomes (2)

  • 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)

  • 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 Outcomes (4)

  • Overall Survival (Safety Lead-In Part)

    up to 24 months

  • Overall Survival (In Triple Negative) (Phase III Part)

    up to 4 years 9 months

  • Progression Free Survival (Phase III Part)

    up to 4 years 9 months

  • Adverse Events (Phase III Part)

    Through study completion, up to 4 years 9 months

Study Arms (2)

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

EXPERIMENTAL
Biological: Futuximab/modotuximabDrug: Trifluridine/Tipiracil

Trifluridine/tipiracil (Phase III part)

ACTIVE COMPARATOR
Drug: Trifluridine/Tipiracil

Interventions

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.

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

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.

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Pregnancy, possibility of becoming pregnant during the study, breastfeeding woman
  • Participants with serious/active/uncontrolled infection
  • Known clinically significant cardiovascular disease or condition
  • Significant gastrointestinal abnormality
  • Patients with other malignancies

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

University of Michigan Oncology Clinic | Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Cleveland Clinic Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, 44195, United States

Location

UZA Edegem

Edegem, 2650, Belgium

Location

UZ Leuven Campus Gasthuisberg

Leuven, 3000, Belgium

Location

CHUUCL Namur site Godinne

Yvoir, 5530, Belgium

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Herning Regional Hospital (Regionhospitalet Godstrup)

Herning, 7400, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

Docrates cancer center

Helsinki, 00180, Finland

Location

TAYS (Tampere University Hospital)

Tampere, 33520, Finland

Location

Magyar Honvédség Egészségügyi Központ Onkológiai Osztály

Budapest, 1062, Hungary

Location

Debreceni Egyetem, Klinikai Központ Onkológiai Klinika

Debrecen, 4032, Hungary

Location

Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudomáyi Kar Oktatókórháza

Kecskemét, 6000, Hungary

Location

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika

Szeged, 6720, Hungary

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Related Publications (1)

  • 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

    BACKGROUND

Related Links

MeSH Terms

Conditions

Colorectal NeoplasmsNeoplasm Metastasis

Interventions

futuximabtrifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Clinical Studies Department
Organization
Institut de Recherches Internationales Servier (I.R.I.S.)

Study Officials

  • Fortunato Ciardiello

    University of Campania Luigi Vanvitelli

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 25, 2022

First Posted

February 4, 2022

Study Start

April 21, 2022

Primary Completion

June 21, 2023

Study Completion

June 21, 2023

Last Updated

August 20, 2024

Results First Posted

March 5, 2024

Record last verified: 2024-07

Data Sharing

IPD Sharing
Will share

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: sponsored by Servier with a first patient enrolled as of 1 January 2004 onwards for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
More information

Available IPD Datasets

Individual Participant Data Set Access
Study Protocol Access
Statistical Analysis Plan Access
Informed Consent Form Access
Clinical Study Report Access
Study-level clinical trial data Access

Locations