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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04073680
• Other study ID #: PT06-01
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2020
• Est. completion date: December 30, 2021

Study information

• Verified date: May 2020
• Source: Petra Pharma
• Contact: Albert Yu, MD
• Phone: 646-440-9218
• Email: ayu[@]petrapharmacorp.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 30, 2021
• Est. primary completion date: July 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Colo-rectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Head and Neck Cancer
• Lung Cancer

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Petra Pharma

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Rate of Laboratory Abnormalities	Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities	30 days after last dose
Primary	Dose confirmation	To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin	6 months
Primary	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	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
Secondary	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
Secondary	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