Clinical trial NCT05223673: Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Futuximab/modotuximab
Trifluridine/tipiracil
Phase III
Safety Lead-In part
S95026
Sym004
Adult
Metastatic
Colorectal
Colorectal Cancer
EGFR
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2022-02-04
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)
timeFrame: End of cycle 1 (Each cycle is up to 28 days)
measure: Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part)
timeFrame: up to 4 years 9 months
Secondary outcomes:
measure: Overall Survival (Safety Lead-In Part)
timeFrame: up to 24 months
measure: Overall Survival (In Triple Negative) (Phase III Part)
timeFrame: up to 4 years 9 months
measure: Progression Free Survival (Phase III Part)
timeFrame: up to 4 years 9 months
measure: Adverse Events (Phase III Part)
timeFrame: Through study completion, up to 4 years 9 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Oncology Clinic | Rogel Cancer Center
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic Cleveland Clinic Lerner College of Medicine
state: Ohio
city: Edegem
country: Belgium
facility: UZA Edegem
city: Leuven
country: Belgium
facility: UZ Leuven Campus Gasthuisberg
city: Yvoir
country: Belgium
facility: CHUUCL Namur site Godinne
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herning
country: Denmark
facility: Herning Regional Hospital (Regionhospitalet Godstrup)
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Helsinki
country: Finland
facility: Docrates cancer center
city: Tampere
country: Finland
facility: TAYS (Tampere University Hospital)
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ Onkológiai Osztály
city: Debrecen
country: Hungary
facility: Debreceni Egyetem, Klinikai Központ Onkológiai Klinika
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudomáyi Kar Oktatókórháza
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
Study officials:
affiliation: University of Campania Luigi Vanvitelli
name: Fortunato Ciardiello
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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