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

A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors With PIK3CA or KRAS Mutations

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Head and Neck Cancer; Lung Cancer; Endometrial Cancer; Colo-rectal Cancer
• Intervention / Treatment: Drug: Serabelisib; Drug: Canagliflozin 300mg

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Albert Yu, MD; Phone Number: 646-440-9218; Email: ayu@petrapharmacorp.com
• Study Contact Backup: Name: Peggy Siemon-Hryczyk, MS; Phone Number: 201-788-6161; Email: psiemonh@petrapharmacorp.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Drug: Canagliflozin 300mg; All subjects will be dosed with 300 mg canagliflozin in combination with serabelisib; Other Names: Invokana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Adverse Events	Safety of serabelisib in combination with canagliflozin as evaluated by incidence of drug-related adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities.	30 days after last dose
Rate of Laboratory Abnormalities	Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities	30 days after last dose
Dose confirmation	To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin	6 months
Tumor Assessments by RESIST	To assess efficacy of serabelisib in combination with canagliflozin in patients with solid tumors with PIK3CA or KRAS mutations	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax Pharmacokinetic assessment	Maximum observed plasma concentration (Cmax) of serabelisib	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
Tmax Pharmacokinetic assessment	Time of maximum observed plasma concentration (Tmax) of serabelisib	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
AUC Pharmacokinetic assessment	Area under the plasma concentration time curve in the dosing interval AUC of serabelisib	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

Collaborators and Investigators

• Sponsor: Petra Pharma
• Investigators: Study Director: Albert Yu, MD, Petra Pharma

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): July 15, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: August 26, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 29, 2019

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin; Serabelisib
• Other Study ID Numbers: PT06-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No