Metastatic Colorectal CancerPhase 3COLSTARNCT05223673
Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer
A Phase 3 study testing Futuximab/modotuximab and Trifluridine/Tipiracil in people with Metastatic Colorectal Cancer, run by Institut de Recherches Internationales Servier at 15 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Futuximab/modotuximab and Trifluridine/Tipiracil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 15 sitesin 6 countries
- Study dates
- 21 Apr 2022to 21 Jun 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Hungary4 sites
Magyar Honvédség Egészségügyi Központ Onkológiai Osztály
Budapest, 1062
Debreceni Egyetem, Klinikai Központ Onkológiai Klinika
Debrecen, 4032
Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudomáyi Kar Oktatókórháza
Kecskemét, 6000
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika
Szeged, 6720
Belgium3 sites
UZA Edegem
Edegem, 2650
UZ Leuven Campus Gasthuisberg
Leuven, 3000
CHUUCL Namur site Godinne
Yvoir, 5530
Denmark3 sites
Rigshospitalet
Copenhagen, 2100
Herning Regional Hospital (Regionhospitalet Godstrup)
Herning, 7400
Odense Universitetshospital
Odense, 5000
United States2 sites
University of Michigan Oncology Clinic | Rogel Cancer Center
Ann Arbor, Michigan, 48109
Cleveland Clinic Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, 44195
Finland2 sites
Docrates cancer center
Helsinki, 00180
TAYS (Tampere University Hospital)
Tampere, 33520
About this study
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
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
- Being tested
- Futuximab/modotuximab, Trifluridine/Tipiracil
- Keywords
- Futuximab/modotuximab, Trifluridine/tipiracil, Phase III, Safety Lead-In part, S95026, Sym004, Adult, Metastatic, Colorectal, Colorectal Cancer, EGFR
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Futuximab/modotuximabBiological
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/TipiracilDrug
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/TipiracilDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts) | Experimental | Not described Receives: Biological: Futuximab/modotuximab; Drug: Trifluridine/Tipiracil |
| Trifluridine/tipiracil (Phase III part) | Active comparator | Not described Receives: Drug: Trifluridine/Tipiracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: up to 4 years 9 months
Secondary outcomes (4)
Overall Survival (Safety Lead-In Part)
Time elapsed from the first IMP intake to death
Measured: up to 24 months
Overall Survival (In Triple Negative) (Phase III Part)
Time elapsed from the date of randomization into the study to disease progression/death
Measured: up to 4 years 9 months
Progression Free Survival (Phase III Part)
Time elapsed from the date of randomization into the study to disease progression/death
Measured: up to 4 years 9 months
Adverse Events (Phase III Part)
Incidence, severity, and relationship of treatment emergent adverse event and treatment emergent serious adverse event
Measured: Through study completion, up to 4 years 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start21 Apr 2022
- Primary completion21 Jun 2023
- Study completion21 Jun 2023
Why it stopped: Sponsor decided to discontinue the study during the Lead-In part and the Phase III part was not started due to strategic reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Responsible party
- Sponsor
- Investigators
- Fortunato Ciardiello, Principal investigator, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05223673
- Sponsor's protocol ID
- CL3-95026-001
- Other IDs
- 2021-003151-41
- Acronym
- COLSTAR
- Status last verified
- Jul 2024
- First submitted
- 25 Jan 2022
- Last updated
- 20 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05223673
- Acronym / sponsor ID
- COLSTAR / CL3-95026-001
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Futuximab/modotuximab, Trifluridine/tipiracil, Phase III, Safety Lead-In part, S95026, Sym004, Adult, Metastatic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decided to discontinue the study during the Lead-In part and the Phase III part was not started due to strategic reasons.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Study start
- 21 Apr 2022 (actual)
- Primary completion
- 21 Jun 2023 (actual)
- Study completion
- 21 Jun 2023 (actual)
- First posted
- 4 Feb 2022 (actual)
- Results
- Posted 5 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts) | Experimental | Biological: Futuximab/modotuximab, Drug: Trifluridine/Tipiracil |
| Trifluridine/tipiracil (Phase III part) | Active comparator | Drug: Trifluridine/Tipiracil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Futuximab/modotuximabConcentrate 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. | Biological | Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts) |
| Trifluridine/TipiracilFilm-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. | Drug | Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts) |
| Trifluridine/TipiracilFilm-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. | Drug | Trifluridine/tipiracil (Phase III part) |
Primary outcome
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)
Time frame: End of cycle 1 (Each cycle is up to 28 days)
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.
Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part)
Time frame: up to 4 years 9 months
Time elapsed from date of randomization until the date of death from any cause
4 secondary outcomes
Overall Survival (Safety Lead-In Part)
Time frame: up to 24 months
Overall Survival (In Triple Negative) (Phase III Part)
Time frame: up to 4 years 9 months
Progression Free Survival (Phase III Part)
Time frame: up to 4 years 9 months
Adverse Events (Phase III Part)
Time frame: Through study completion, up to 4 years 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundCiardiello 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
- Find Results on Servier Clinical Trial Data websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fortunato Ciardiello principal investigator
University of Campania Luigi Vanvitelli
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Futuximab/modotuximab and Trifluridine/Tipiracil in people with Metastatic Colorectal Cancer, run by Institut de Recherches Internationales Servier at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Hungary, Belgium, Denmark, United States, Finland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part) (time frame: End of cycle 1 (Each cycle is up to 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05223673, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.