Colorectal Cancer
Conditions
Keywords
PIK3CA-mutated Colorectal Cancer
Brief summary
This is a blinded Phase 2 study designed to evaluate the safety and efficacy of inavolisib with bevacizumab and chemotherapy, in participants with metastatic colorectal cancer (mCRC) whose tumors have a PIK3CA mutation. The study has a safety run-in period followed by a randomized period.
Interventions
DRUGPlacebo
Participants will receive Placebo as per the schedule mentioned in the protocol.
DRUGInavolisib
Participants will receive Inavolisib as per the schedule mentioned in the protocol.
DRUGBevacizumab
Participants will receive Bevacizumab as per the schedule mentioned in the protocol.
DRUGFOLFOX
Participants will receive FOLFOX as per the schedule mentioned in the protocol.
DRUGFOLFIRI
Participants will receive FOLFIRI as per the schedule mentioned in the protocol.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) \<=1 * Histologically confirmed adenocarcinoma originating in the colon or rectum of the Stage 4 ( treatment plan does not include resection or curative ablation) per American Joint Committee on Cancer (AJCC) v8 * Measurable disease per RECIST v1.1 * No prior systemic therapy in the metastatic setting * Confirmation of biomarker eligibility: documentation of a PIK3CA mutation from either central testing of tissue, or from a validated historically obtained (pre-existing) test of tumor tissue or blood may be used to confirm eligibility * Adequate hematologic and organ function within 14 days prior to initiation of study treatment * Agreement to adhere to the contraception requirements
Exclusion criteria
* Biomarker eligibility as per definition * Type 2 diabetes requiring ongoing systemic treatment at the time of study entry or any history of Type 1 diabetes * Residual Grade 2 or higher neuropathy due to prior oxaliplatin exposure (unless the participant is planned to be treated with FOLFIRI) * Symptomatic, untreated, or actively progressing CNS metastases * History of gastrointestinal (GI) fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 1 of Cycle 1 * Treatment with strong cytochrome P450 (CYP) 3A4 inducers or strong CYP3A4 inhibitors within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment (only for patients who will receive FOLFIRI) * Known HIV positive status with exceptions for well controlled and on stable treatment * History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run-in Period: Percentage of Participants With Adverse Events (AEs) | Approximately 4 Years | — |
| Percentage of Participants With an Objective Response Rate | From Baseline Untill Radiographic Disease Progression (Approximately 4 Years) | The percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From Baseline Untill Radiographic Disease Progression (up to Approximately 4 Years) | Time from randomization to death from any cause or the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 (whichever occurs first) |
| Randomized Phase: Overall Survival (OS) | From Baseline Untill Death (up to Approximately 4 Years) | Defined as the time from randomization to death from any cause |
| Randomized Phase: Disease Control Rate (DCR) | From Baseline Untill Disease Progression (up to Approximately 4 Years) | Defined as the percentage of participants with stable disease for \>=12 weeks or a CR or PR as determined by the investigator according to RECIST v1.1 |
| Randomized Phase: Duration of Response (DOR) | From Baseline Untill Disease Progression or Death (up to Approximately 4 Years) | Defined as the time from the first occurrence of a documented confirmed OR to death from any cause or the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, (whichever occurs first) |
| Randomized Phase: Percentage of Participants With AEs | From Baseline up to 90 Days After the Final Dose of study treatment or Until Initiation of Another Anti-cancer Therapy (up to Approximately 4 Years) | — |
| Percentage of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) | Up to Approximately 4 Years | — |
| Percentage of Participants Troubled by Treatment Symptoms, as Assessed by Single Item European Organisation for Research and Treatment of Cancer Item Library 46 (EORTC IL46) | Up to Approximately 4 Years | — |
| Change From Baseline in Symptomatic Treatment Toxicities as Assessed by PRO-CTCAE | Baseline up to Approximately 4 Years | — |
| Change From Baseline in Treatment Side-effect Bother as Assessed by EORTC IL46 item | Baseline up to Approximately 4 Years | — |
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed