Brief Title
A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors
Official Title
A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors With PIK3CA or KRAS Mutations
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Rate of Adverse Events
Secondary Outcome
Cmax Pharmacokinetic assessment
Condition
Breast Cancer
Intervention
Serabelisib
Study Arms / Comparison Groups
Serabelisib
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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
September 1, 2020
Completion Date
December 30, 2021
Primary Completion Date
July 15, 2021
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Albert Yu, MD, 646-440-9218, [email protected]
Administrative Informations
NCT ID
NCT04073680
Organization ID
PT06-01
Responsible Party
Sponsor
Study Sponsor
Petra Pharma
Study Sponsor
Albert Yu, MD, Study Director, Petra Pharma
Verification Date
May 2020