Clinical trial NCT04073680: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Endometrial Cancer
Lung Cancer
Colo-rectal Cancer
Head and Neck Cancer
Lead sponsor: Petra Pharma
Sponsor class: INDUSTRY
First posted: 2019-08-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of Adverse Events
timeFrame: 30 days after last dose
measure: Rate of Laboratory Abnormalities
timeFrame: 30 days after last dose
measure: Dose confirmation
timeFrame: 6 months
measure: Tumor Assessments by RESIST
timeFrame: 2 years
Secondary outcomes:
measure: Cmax Pharmacokinetic assessment
timeFrame: Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours
measure: Tmax Pharmacokinetic assessment
timeFrame: Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours
measure: AUC Pharmacokinetic assessment
timeFrame: Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours
Other outcomes:
Locations:
Study officials:
affiliation: Petra Pharma
name: Albert Yu, MD
role: STUDY_DIRECTOR
References: