Back to results

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

Primary Purpose

Breast Cancer, Endometrial Cancer, Lung Cancer

Status

Unknown status

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Serabelisib

Canagliflozin 300mg

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have histologically or cytologically confirmed locally advanced or metastatic solid tumors.
Have a tumor harboring a mutation in PIK3CA or KRAS genes.
Have received prior therapy and have recurrent or persistent disease without standard therapies available, or are ineligible to receive standard therapies.
Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤2
Have adequate organ function.
Have adequate birth control during the course of the study.

12. Are able to receive canagliflozin

Exclusion Criteria:

Diagnosis of primary brain tumor
Untreated brain metastasis or history of leptomeningeal disease
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.
Have diabetes mellitus requiring insulin therapy
Have diabetes mellitus requiring insulin secretagogue therapy
Have poorly controlled diabetes mellitus defined as glycosylated hemoglobin A1c (HbA1c) >7.5%
Have a secondary malignancy requiring therapy or are unstable without therapy.
Known impaired cardiac function or clinically significant cardiac disease.
Myocardial infarction or unstable angina within 6 months before the first administration of study drug.
Pregnant (positive serum pregnancy test) or breastfeeding

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Serabelisib

Arm 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

Outcomes

Primary Outcome Measures

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.

Rate of Laboratory Abnormalities

Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities

Dose confirmation

To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin

Tumor Assessments by RESIST

To assess efficacy of serabelisib in combination with canagliflozin in patients with solid tumors with PIK3CA or KRAS mutations

Secondary Outcome Measures

Cmax Pharmacokinetic assessment

Maximum observed plasma concentration (Cmax) of serabelisib

Tmax Pharmacokinetic assessment

Time of maximum observed plasma concentration (Tmax) of serabelisib

AUC Pharmacokinetic assessment

Area under the plasma concentration time curve in the dosing interval AUC of serabelisib

Full Information

NCT ID

NCT04073680

First Posted

August 26, 2019

Last Updated

May 20, 2020

Sponsor

Petra Pharma

1. Study Identification

Unique Protocol Identification Number

NCT04073680

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Unknown status

Study Start Date

September 1, 2020 (Anticipated)

Primary Completion Date

July 15, 2021 (Anticipated)

Study Completion Date

December 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Petra Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Serabelisib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Serabelisib

Intervention Description

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

Intervention Name(s)

Canagliflozin 300mg

Other Intervention Name(s)

Invokana

Intervention Description

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

Primary Outcome Measure Information:

Title

Rate of Adverse Events

Description

Time Frame

30 days after last dose

Title

Rate of Laboratory Abnormalities

Description

Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities

Time Frame

30 days after last dose

Title

Dose confirmation

Description

To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin

Time Frame

6 months

Title

Tumor Assessments by RESIST

Description

To assess efficacy of serabelisib in combination with canagliflozin in patients with solid tumors with PIK3CA or KRAS mutations

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Cmax Pharmacokinetic assessment

Description

Maximum observed plasma concentration (Cmax) of serabelisib

Time Frame

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

Title

Tmax Pharmacokinetic assessment

Description

Time of maximum observed plasma concentration (Tmax) of serabelisib

Time Frame

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

Title

AUC Pharmacokinetic assessment

Description

Area under the plasma concentration time curve in the dosing interval AUC of serabelisib

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have histologically or cytologically confirmed locally advanced or metastatic solid tumors. Have a tumor harboring a mutation in PIK3CA or KRAS genes. Have received prior therapy and have recurrent or persistent disease without standard therapies available, or are ineligible to receive standard therapies. Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤2 Have adequate organ function. Have adequate birth control during the course of the study. 12. Are able to receive canagliflozin Exclusion Criteria: Diagnosis of primary brain tumor Untreated brain metastasis or history of leptomeningeal disease 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. Have diabetes mellitus requiring insulin therapy Have diabetes mellitus requiring insulin secretagogue therapy Have poorly controlled diabetes mellitus defined as glycosylated hemoglobin A1c (HbA1c) >7.5% Have a secondary malignancy requiring therapy or are unstable without therapy. Known impaired cardiac function or clinically significant cardiac disease. Myocardial infarction or unstable angina within 6 months before the first administration of study drug. Pregnant (positive serum pregnancy test) or breastfeeding

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Albert Yu, MD

Phone

646-440-9218

ayu@petrapharmacorp.com

First Name & Middle Initial & Last Name or Official Title & Degree

Peggy Siemon-Hryczyk, MS

Phone

201-788-6161

psiemonh@petrapharmacorp.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Albert Yu, MD

Organizational Affiliation

Petra Pharma

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs