A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors

Petra Pharma

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Endometrial Cancer; Breast Cancer; Colo-rectal Cancer; Lung Cancer; Head and Neck Cancer

Treatments: Drug: Serabelisib; Drug: Canagliflozin 300mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04073680

PT06-01

Details and patient eligibility

About

This study aims to test the hypothesis that combining serabelisib, a PI3K alpha isoform inhibitor, with an SGLT2 inhibitor, canagliflozin will improve efficacy in the treatment of patients with advanced solid tumors.

Full description

This study aims to test the hypothesis that controlling the glucose/insulin feedback will enhance the efficacy of PI3K inhibition in treating solid tumors. The treatment consists of serabelisib, a PI3K alpha isoform (PI3Kα) inhibitor, combined with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. The study will assess the safety and efficacy of the combination in adult patients with advanced solid tumors harboring mutations that may be dependent on PI3Kα activity: PIK3CA mutations and KRAS mutations.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Have histologically or cytologically confirmed locally advanced or metastatic solid tumors.

2. Have a tumor harboring a mutation in PIK3CA or KRAS genes.

3. Have received prior therapy and have recurrent or persistent disease without standard therapies available, or are ineligible to receive standard therapies.

4. Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

5. Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤2

6. Have adequate organ function.

7. Have adequate birth control during the course of the study.

8. Are able to receive canagliflozin

Exclusion criteria

1. Diagnosis of primary brain tumor
2. Untreated brain metastasis or history of leptomeningeal disease
3. Have received prior chemotherapy within 28 days or other anticancer agents within 28 days of 5 half lives (whichever is the shorter duration) before the first administration of study drug. The exception is patients in Cohort 4 (PIK3CA-mutated breast cancer) are allowed to receive ongoing endocrine therapy.
4. Have diabetes mellitus requiring insulin therapy
5. Have diabetes mellitus requiring insulin secretagogue therapy
6. Have poorly controlled diabetes mellitus defined as glycosylated hemoglobin A1c (HbA1c) >7.5%
7. Have a secondary malignancy requiring therapy or are unstable without therapy.
8. Known impaired cardiac function or clinically significant cardiac disease.
9. Myocardial infarction or unstable angina within 6 months before the first administration of study drug.
10. Pregnant (positive serum pregnancy test) or breastfeeding

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Serabelisib

Experimental group

Description:

Part 1 is dose escalation of Serabelisib Cohort 1 = 600mg; Cohort 2 = 900mg; Cohort 3 = 1200mg Part 2 is expansion of mutational cohorts with selected dose as follows: Cohort 4 = PIK3CA-mutated breast cancer; Cohort 5 = PIK3CA-mutated Non breast cancer; Cohort 6 = KRAS mutated

Treatment:

Drug: Serabelisib

Drug: Canagliflozin 300mg