Clinical trial NCT04495621: MEN1611 With Cetuximab in Metastatic Colorectal Cancer (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer
PI3K Inhibitor
PIK3CA mutated
MEN1611
Cetuximab
anti-EGFR
mCRC
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2020-08-03
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab
timeFrame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
measure: Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab
timeFrame: Up to 37 Months
measure: Phase 1b: Number of Participants With DLTs for MEN1611
timeFrame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
Secondary outcomes:
measure: Plasma Concentration of MEN1611 in Combination With Cetuximab
timeFrame: Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)
measure: Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab
timeFrame: Up to 37 Months
measure: Duration of Response (DOR) of MEN1611 in Combination With Cetuximab
timeFrame: Up to 37 months
measure: Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab
timeFrame: Up to 37 months
measure: Overall Survival (OS) of MEN1611 in Combination With Cetuximab
timeFrame: Up to 37 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Anaheim
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Angers
country: France
facility: ICO - Site Paul Papin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Saint-Herblain
country: France
facility: ICO - Site René Gauducheau
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen Campus Grosshadern
city: Munich
country: Germany
facility: Klinikum rechts der Isar der TU
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Genoa
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
city: Milan
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud Nijmegen
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Skórzewo
country: Poland
facility: Examen sp. z o.o.
city: Warsaw
country: Poland
facility: Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Vall d' Hebron Institute of Oncology (VHIO), Barcelona, Spain
name: Josep Tabernero, MD, PhD
role: STUDY_CHAIR
References: