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

Sponsor

Menarini Group (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04495621

Collaborator

(none)

Enrollment

Locations

Arm

35.4

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: MEN1611 Drug: Cetuximab	Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort ExpansionStep 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 20, 2020

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEN1611 MEN1611 + Cetuximab	Drug: MEN1611 MEN1611 oral dose administered twice daily for a continuous 28-day cycle. Drug: Cetuximab Cetuximab solution for infusion administered weekly via IV infusion.

Arm

Intervention/Treatment

Experimental: MEN1611

MEN1611 + Cetuximab

Drug: MEN1611

MEN1611 oral dose administered twice daily for a continuous 28-day cycle.

Drug: Cetuximab

Cetuximab solution for infusion administered weekly via IV infusion.

Outcome Measures

Primary Outcome Measures

Determination of recommended phase II dose (RP2D) [28 Days]
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.
Best overall response rate (ORR) according to RECIST v.1.1 [36 Months]
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.

Secondary Outcome Measures

Incidence of treatment emergent adverse events (TEAEs) [36 Months]
Assessment of the tolerability of MEN1611 in combination with cetuximab according to NCI CTCAE v5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85054
2	The Oncology Institute of Hope and Innovation	Anaheim	California	United States	92801
3	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington	United States	98405
4	ICO - Site Paul Papin	Angers		France	49055
5	Centre Georges François Leclerc	Dijon		France	21000
6	ICO - Site René Gauducheau	Saint-Herblain		France	44800
7	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin		Germany	12203
8	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden		Germany	01307
9	Klinikum der Universitaet Muenchen Campus Grosshadern	Munich		Germany	81377
10	Munich	Munich		Germany	81675
11	Universitaetsklinikum Tuebingen	Tuebingen		Germany	72076
12	Azienda Ospedaliero Universitaria San Martino	Genoa		Italy	16132
13	Istituto Europeo di Oncologia (IEO)	Milan		Italy	20141
14	Azienda Socio Sanitaria Territoriale Niguarda	Milan		Italy	20162
15	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56126
16	Istituto Clinico Humanitas	Rozzano		Italy	20089
17	Amsterdam University Medical Center	Amsterdam		Netherlands	1105 AZ
18	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
19	Radboud Nijmegen	Nijmegen		Netherlands	6525 GA
20	Erasmus Medisch Centrum	Rotterdam		Netherlands	3015 GD
21	Examen sp. z o.o.	Skórzewo		Poland	60-185
22	Centrum Onkologii-Instytut im.M.Sklodowskiej Curie	Warsaw		Poland	00-001
23	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
24	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
25	Fundacion Jimenez Diaz	Madrid		Spain	28040
26	Centro Integral Oncologico Clara Campal	Madrid		Spain	28050
27	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010