Metastatic Colorectal CancerPhase 1/2C-PRECISE-01NCT04495621

MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)

A Phase 1/2 study testing MEN1611 and Cetuximab in people with Metastatic Colorectal Cancer, run by Menarini Group at 28 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Open-label, dose-confirmation and cohort expansion, multicenter, Phase Ib/II study to assess the anti-tumor activity and safety of MEN1611 in combination with cetuximab for the treatment of participants with phosphatidylinositol 3-kinase, catalytic, alpha polypeptide gene (PIK3CA)-mutated metastatic colorectal cancer. 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?: MEN1611 and Cetuximab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 28 sitesin 7 countries
Study dates: 20 Jul 2020to 27 Feb 2024
Phase: Phase 1/2
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

Main Inclusion Criteria:

Histological documentation of adenocarcinoma of the colon or rectum.
Progression or recurrence following prior irinotecan, oxaliplatin, 5-fluorouracil (5-FU) and anti-epidermal growth factor receptor (EGFR) containing regimens for metastatic disease.
Best response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria to the last anti-EGFR containing regimen of partial response or stable disease for at least 4 months.
Measurable disease according to RECIST criteria.
N-K-RAS (exons 2, 3 and 4) and BRAF wild-type and PIK3CA mutated.
Eastern Cooperative Oncology Group performance status of 0 or 1.

Main Exclusion Criteria:

Previous treatment with PI3K inhibitor.
Brain metastases, unless treated >4 weeks before screening visit and only if clinically stable and not receiving corticosteroids.
National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 Grade ≥2 diarrhea.
History of significant, uncontrolled or active cardiovascular disease.
Known active or uncontrolled pulmonary dysfunction.
Uncontrolled diabetes mellitus (glycated hemoglobin >7%) and fasting plasma glucose >126 milligrams/deciliter.
Known history of human immunodeficiency virus infection or active infection with hepatitis C virus or hepatitis B virus.
Concurrent chronic immunosuppressive treatment either with steroids or other immunosuppressive agents.

Trial locations and contacts

28 sites in 7 countries.

Country

City, postcode or hospital

28 sites in 7 countries

Germany6 sites

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, 12203
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, 01307
Asklepios Klinik Altona
Hamburg, 22763
Klinikum der Universitaet Muenchen Campus Grosshadern
Munich, 81377
Klinikum rechts der Isar der TU
Munich, 81675
Universitaetsklinikum Tuebingen
Tübingen, 72076

Other trials in Germany

Italy5 sites

Azienda Ospedaliero Universitaria San Martino
Genoa, 16132
Istituto Europeo di Oncologia (IEO)
Milan, 20141
Azienda Socio Sanitaria Territoriale Niguarda
Milan, 20162
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
Istituto Clinico Humanitas
Rozzano, 20089

Other trials in Italy

Spain5 sites

Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario Ramon y Cajal
Madrid, 28034
Fundacion Jimenez Diaz
Madrid, 28040
Centro Integral Oncologico Clara Campal
Madrid, 28050
Hospital Clinico Universitario de Valencia
Valencia, 46010

Other trials in Spain

Netherlands4 sites

Amsterdam University Medical Center
Amsterdam, 1105 AZ
Maastricht University Medical Center
Maastricht, 6229 HX
Radboud Nijmegen
Nijmegen, 6525 GA
Erasmus Medisch Centrum
Rotterdam, 3015 GD

Other trials in Netherlands

United States3 sites

The Oncology Institute of Hope and Innovation
Anaheim, California, 92801
Mayo Clinic Arizona
Phoenix, Arizona, 85054
MultiCare Health System Institute for Research and Innovation
Tacoma, Washington, 98405

Other trials in United States

France3 sites

ICO - Site Paul Papin
Angers, 49055
Centre Georges François Leclerc
Dijon, 21000
ICO - Site René Gauducheau
Saint-Herblain, 44800

Other trials in France

Poland2 sites

Examen sp. z o.o.
Skórzewo, 60-185
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
Warsaw, 00-001

Other trials in Poland

About this study

Official title: Open-label, Multicentre, Phase Ib/II Study of MEN1611, a PI3K Inhibitor, and Cetuximab in Patients With PIK3CA Mutated Metastatic Colorectal Cancer Failing Irinotecan, Oxaliplatin, 5-FU and Anti-EGFR Containing Regimens

Read the detailed description

This Phase Ib/II study investigated the anti-tumor activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male participants affected by PIK3CA-mutated, neuroblastoma-Kristen-rat sarcoma virus (N-K-RAS) wild-type, and BRAF wild-type metastatic colorectal cancer.

MEN1611 is a potent, selective class I phosphoinositide 3-kinase (PI3K) inhibitor. The maximum tolerated dose of MEN1611 given as single agent was assessed in a Phase I trial in participants with advanced solid tumors.

This Phase Ib/II started with a dose confirmation part (Step 1) to identify the recommended phase 2 dose of MEN1611 given in combination with cetuximab.

The study continued with a cohort expansion (Step 2) to explore the anti-tumor activity of the selected MEN1611 dose level combined with cetuximab with further assessment of safety and tolerability.

Conditions: Metastatic Colorectal Cancer
Being tested: MEN1611, Cetuximab
Keywords: Metastatic Colorectal Cancer, PI3K Inhibitor, PIK3CA mutated, MEN1611, Cetuximab, anti-EGFR, mCRC
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MEN1611Drug
MEN1611 oral dose administered twice daily for a continuous 28-day cycle.
CetuximabDrug
Cetuximab solution for infusion administered weekly via intravenous infusion.

Study groups in NCT04495621
Study group	Role	What they receive
MEN1611	Experimental	MEN1611 + Cetuximab Receives: Drug: MEN1611; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.
Measured: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab
The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
Measured: Up to 37 Months
Phase 1b: Number of Participants With DLTs for MEN1611
A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting >7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.
Measured: Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Secondary outcomes (5)

Plasma Concentration of MEN1611 in Combination With Cetuximab
Blood samples were taken for the analyses of MEN1611 in plasma at designated time points. Results are reported as nanograms/millilitre (ng/mL).
Measured: Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)
Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab
DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated based on the sum of the CR, PR, and SD rates according to local assessment.
Measured: Up to 37 Months
Duration of Response (DOR) of MEN1611 in Combination With Cetuximab
DOR was defined as the time from confirmation of a PR, CR or SD as locally assessed, until the disease had been shown to progress following treatment. Participants with a previous response who did not show a relapse or died without recording a relapse were censored at their last available relapse-free tumor assessment date. Participants with only one tumor assessment after baseline showing a PD were not included in the calculation.
Measured: Up to 37 months
Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab
PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumor assessment date.
Measured: Up to 37 months
Overall Survival (OS) of MEN1611 in Combination With Cetuximab
OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive that had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive was considered.
Measured: Up to 37 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Jul 202027 Feb 2024

First posted3 Aug 2020
Study start20 Jul 2020
Primary completion12 Jan 2024
Study completion27 Feb 2024

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.
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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04495621
Sponsor's protocol ID: MEN1611-02
Other IDs: 2019-003727-38, 2019
Acronym: C-PRECISE-01
Status last verified: Apr 2025
First submitted: 30 Jun 2020
Last updated: 1 May 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Metastatic Colorectal Cancer
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Not yet recruitingPhase 1/2
A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
CRC

All Metastatic Colorectal Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 1 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-label, Multicentre, Phase Ib/II Study of MEN1611, a PI3K Inhibitor, and Cetuximab in Patients With PIK3CA Mutated Metastatic Colorectal Cancer Failing Irinotecan, Oxaliplatin, 5-FU and Anti-EGFR Containing Regimens
ClinicalTrials.gov ID: NCT04495621
Acronym / sponsor ID: C-PRECISE-01 / MEN1611-02
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer, PI3K Inhibitor, PIK3CA mutated, MEN1611, Cetuximab, anti-EGFR, mCRC
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Menarini GroupIndustry (pharma, biotech, devices)
Study start: 20 Jul 2020 (actual)
Primary completion: 12 Jan 2024 (actual)
Study completion: 27 Feb 2024 (actual)
First posted: 3 Aug 2020 (actual)
Results: Posted 1 May 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This Phase Ib/II started with a dose confirmation part (Step 1) to identify the recommended phase 2 dose of MEN1611 given in combination with cetuximab.

The study continued with a cohort expansion (Step 2) to explore the anti-tumor activity of the selected MEN1611 dose level combined with cetuximab with further assessment of safety and tolerability.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion

Arm	Type	Receives
MEN1611	Experimental	Drug: MEN1611, Drug: CetuximabMEN1611 + Cetuximab

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

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
MEN1611MEN1611 oral dose administered twice daily for a continuous 28-day cycle.	Drug	MEN1611
CetuximabCetuximab solution for infusion administered weekly via intravenous infusion.	Drug	MEN1611

Primary outcome

Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab
Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab
Time frame: Up to 37 Months
The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
Phase 1b: Number of Participants With DLTs for MEN1611
Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting >7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.

5 secondary outcomes

Plasma Concentration of MEN1611 in Combination With Cetuximab
Time frame: Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)
Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab
Time frame: Up to 37 Months
Duration of Response (DOR) of MEN1611 in Combination With Cetuximab
Time frame: Up to 37 months
Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab
Time frame: Up to 37 months
Overall Survival (OS) of MEN1611 in Combination With Cetuximab
Time frame: Up to 37 months

Results and safety

Results posted to the registry on 1 May 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1b (Dose Confirmation)	7	0
Phase 2 (Cohort Expansion)	22	0

Primary outcome: Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab

Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle). Number. Unit: mg

Measure	Phase 1b (Dose Confirmation) n = 7
Value	48

Population analysed: Safety Population: all participants who received at least 1 dose of MEN1611. As pre-specified, RP2D data were collected and are reported for 'Phase 1b (Dose Confirmation)' cohort only.

Primary outcome: Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab

Time frame: Up to 37 Months. Number. Unit: percentage of participants

Measure	Phase 1b (Dose Confirmation) n = 5	Phase 2 (Cohort Expansion) n = 14
Complete Response	0.0	7.1
Partial Response	40.0	7.1
Stable Disease	40.0	57.1
Progressive Disease	20.0	28.6

Population analysed: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

Primary outcome: Phase 1b: Number of Participants With DLTs for MEN1611

Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle). Count of participants. Unit: Participants

Measure	Phase 1b (Dose Confirmation) n = 6
Value	0

Population analysed: Dose-limiting Toxicity (DLT) Population: all participants who received at least 80% of MEN1611 and 75% of cetuximab during Cycle 1 with a safety follow-up of 28 days after the first administration of the study treatment. Any participant who experienced DLT was also considered evaluable, regardless of the dose received. As pre-specified, data were collected and reported for the 'Phase 1b (Dose Confirmation)' cohort only.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Day 1 to the end of study (37 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1b (Dose Confirmation)	5 of 7 (71.4%)	7 of 7 (100%)	7 of 7
Phase 2 (Cohort Expansion)	11 of 22 (50%)	22 of 22 (100%)	11 of 22

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Metastatic Colorectal Cancer

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Metastatic Colorectal Cancer
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Not yet recruitingPhase 1/2
A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
CRC

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.

Josep Tabernero, MD, PhD study chair

Vall d' Hebron Institute of Oncology (VHIO), Barcelona, Spain

28 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MEN1611 and Cetuximab in people with Metastatic Colorectal Cancer, run by Menarini Group at 28 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: finished, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Germany, Italy, Spain, Netherlands, United States and 2 more countries. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 1 May 2025). 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?

Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab (time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)). The study lists 3 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 NCT04495621.

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 1 May 2025.