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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04073680
Recruitment Status : Not yet recruiting
First Posted : August 29, 2019
Last Update Posted : May 21, 2020
Sponsor:
Information provided by (Responsible Party):
Petra Pharma

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Endometrial Cancer Lung Cancer Colo-rectal Cancer Head and Neck Cancer Drug: Serabelisib Drug: Canagliflozin 300mg Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors With PIK3CA or KRAS Mutations
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : July 15, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


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 Name: Invokana




Primary Outcome Measures :
  1. Rate of Adverse Events [ Time Frame: 30 days after last dose ]
    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.

  2. Rate of Laboratory Abnormalities [ Time Frame: 30 days after last dose ]
    Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities

  3. Dose confirmation [ Time Frame: 6 months ]
    To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin

  4. Tumor Assessments by RESIST [ Time Frame: 2 years ]
    To assess efficacy of serabelisib in combination with canagliflozin in patients with solid tumors with PIK3CA or KRAS mutations


Secondary Outcome Measures :
  1. Cmax Pharmacokinetic assessment [ 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 ]
    Maximum observed plasma concentration (Cmax) of serabelisib

  2. Tmax Pharmacokinetic assessment [ 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 ]
    Time of maximum observed plasma concentration (Tmax) of serabelisib

  3. AUC Pharmacokinetic assessment [ 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 ]
    Area under the plasma concentration time curve in the dosing interval AUC of serabelisib



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04073680


Contacts
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Contact: Albert Yu, MD 646-440-9218 ayu@petrapharmacorp.com
Contact: Peggy Siemon-Hryczyk, MS 201-788-6161 psiemonh@petrapharmacorp.com

Sponsors and Collaborators
Petra Pharma
Investigators
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Study Director: Albert Yu, MD Petra Pharma
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Responsible Party: Petra Pharma
ClinicalTrials.gov Identifier: NCT04073680    
Other Study ID Numbers: PT06-01
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms by Site
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Canagliflozin
Serabelisib
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Enzyme Inhibitors