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

Metastatic Colorectal Cancer Clinical Trial

— C-PRECISE-01  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04495621
• Other study ID #: MEN1611-02
• Secondary ID: 2019-003727-38
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 20, 2020
• Est. completion date: February 27, 2024

Study information

• Verified date: May 2024
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, dose-confirmation and cohort expansion, multicentre, Phase Ib/II study to assess the anti-tumour activity and safety of MEN1611 in combination with cetuximab for the treatment of patients with PIK3CA mutated metastatic colorectal cancer.

Description:

This Phase Ib/II study will investigate the anti-tumour activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male patients affected by PIK3CA mutated, 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 (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors.

This Phase Ib/II will start with a dose confirmation part (Step 1) to identify the RP2D of MEN1611 given in combination with cetuximab.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 27, 2024
• Est. primary completion date: January 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

• Histological documentation of adenocarcinoma of the colon or rectum.

• Progression or recurrence following prior irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens for metastatic disease.

• Best response according to Response Evaluation Criteria in Solid Tumours 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 (ECOG) performance status (PS) 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.

• NCI CTCAE v5.0 Grade = 2 diarrhoea.

• History of significant, uncontrolled or active cardiovascular disease.

• Known active or uncontrolled pulmonary dysfunction.

• Uncontrolled diabetes mellitus (HbA1c > 7%) and fasting plasma glucose > 126 mg/dL.

• 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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• MEN1611
MEN1611 oral dose administered twice daily for a continuous 28-day cycle.
• Cetuximab
Cetuximab solution for infusion administered weekly via IV infusion.

Locations

Country	Name	City	State
France	ICO - Site Paul Papin	Angers
France	Centre Georges François Leclerc	Dijon
France	ICO - Site René Gauducheau	Saint-Herblain
Germany	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Klinikum der Universitaet Muenchen Campus Grosshadern	Munich
Germany	Munich	Munich
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Italy	Azienda Ospedaliero Universitaria San Martino	Genoa
Italy	Azienda Socio Sanitaria Territoriale Niguarda	Milan
Italy	Istituto Europeo di Oncologia (IEO)	Milan
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Istituto Clinico Humanitas	Rozzano
Netherlands	Amsterdam University Medical Center	Amsterdam
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboud Nijmegen	Nijmegen
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	Examen sp. z o.o.	Skórzewo
Poland	Centrum Onkologii-Instytut im.M.Sklodowskiej Curie	Warsaw
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	The Oncology Institute of Hope and Innovation	Anaheim	California
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of recommended phase II dose (RP2D)	Determination of the recommended phase II dose of MEN1611 when administered orally in combination with cetuximab to patients with PIK3CA mutated colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.	28 Days
Primary	Best overall response rate (ORR) according to RECIST v.1.1	Assessment of the anti-tumour activity of MEN1611 in combination with cetuximab in patients with PIK3CA mutated metastatic colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.	36 Months
Secondary	Incidence of treatment emergent adverse events (TEAEs)	Assessment of the tolerability of MEN1611 in combination with cetuximab according to NCI CTCAE v5.0.	36 Months