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

NCT ID: NCT04073680

Last Updated: 2020-05-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2021-12-30

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Serabelisib

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

Group Type: EXPERIMENTAL

Serabelisib

Intervention Type: DRUG

Subjects will be dosed with Serabelisib on 3 consecutive days a week in a 28 day cycle until tumor progression. in combination with Canagliflozin 300mg, both are oral medications

Canagliflozin 300mg

Intervention Type: DRUG

All subjects will be dosed with 300 mg canagliflozin in combination with serabelisib

Interventions

Serabelisib

Subjects will be dosed with Serabelisib on 3 consecutive days a week in a 28 day cycle until tumor progression. in combination with Canagliflozin 300mg, both are oral medications

Intervention Type: DRUG

Canagliflozin 300mg

All subjects will be dosed with 300 mg canagliflozin in combination with serabelisib

Intervention Type: DRUG

Other Intervention Names

Invokana

Eligibility Criteria

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.

12. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Petra Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert Yu, MD

Role: STUDY_DIRECTOR

Petra Pharma

Central Contacts

Albert Yu, MD

Role: CONTACT

ayu@petrapharmacorp.com

646-440-9218

Peggy Siemon-Hryczyk, MS

Role: CONTACT

psiemonh@petrapharmacorp.com

201-788-6161

Other Identifiers

PT06-01

Identifier Type: -

Identifier Source: org_study_id