search
Back to results

Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Loss of Expression (MATCH-Subprotocol P)

Primary Purpose

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PI3K-beta Inhibitor GSK2636771
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lymphoma

Eligibility Criteria

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

Inclusion Criteria:

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
  • Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
  • Patients must have complete loss of cytoplasmic and nuclear PTEN staining on immunohistochemistry as determined by the MATCH PTEN immunohistochemistry (IHC) assay performed at MD Anderson. Patients can have any PTEN mutation or deletion status, but MUST have PTEN loss by IHC
  • Patients must have hemoglobin >= 9 g/dL
  • Patients must have a serum creatinine that is < 1.5 x upper limit of normal (ULN) or have a 24-hour creatinine clearance of > 50 mL/min

Exclusion Criteria:

  • Patients must not have known hypersensitivity to GSK2636771 or compounds of similar chemical or biologic composition
  • Patients must not have tumors harboring co-existing aberrations activating the PI3K/MTOR and MAPK pathways, such as PIK3CA, PIK3R1, BRAF, KRAS and AKT1, TSC1/2, mTOR, NF2, NRAS, HRAS, NF1

  • Patients must not have received prior treatment with agents targeting the PI3K beta, AKT, or mTOR:

    • This includes (but is not limited to):

      • mTOR inhibitors: temsirolimus, everolimus, ridaforolimus, sirolimus, salirasib, CC-223, INK128, DS-3078, CC-115, AZD-2014

    • Dual PI3K/mTOR inhibitors: BEZ235, XL-765, GDC 0980, PF-04691502, GSK 2126458, Quinacrine, PKI-587, P-P7170, LY3023414, GDC 0084, DS 7423, CBLC-137

      • Pan-PI3K inhibitors: BKM-120 (buparlisib), PX-866, XL-147, GDC-0941 (pictilisib), BAY-806946, ZSTK-474, WX 037, SRX5000, SRX2523, AMG511, PQR308, BAY 94-9343
      • PI3K inhibitors with beta isoform activity: prior GSK2636771 is not allowed, nor is GS-9820, PQR3XX, KAR4139

    • The following previous treatments are allowed:

      • BYL719 (PI3Kalpha inhibitor)
      • GDC-0032 (PI3Kalpha inhibitor)
      • INK1117 (PI3Kalpha inhibitor)
      • Idelalisib (PI3Kdelta inhibitor)
      • IPI-125 (PI3K gamma delta inhibitor)
      • TGR1202 (PI3Kdelta inhibitor)
      • SRX2558 (PI3Kdelta inhibitor)
      • RP6530 (PI3K gamma delta inhibitor)
      • PWT143 (PI3Kdelta inhibitor)
      • IPI443 (PI3K gamma delta inhibitor)
      • GNE293 (PI3Kdelta inhibitor)
  • Patients with a history of interstitial lung disease or pneumonitis are excluded

  • Patients must not have any congenital platelet function defects and cannot be on any of the following anti-platelet drugs: clopidogrel, ticlopidine, prasugrel, that act at platelet purinergic receptors

    • Any need for starting anti-platelet therapy in a patient enrolled to this arm will have to be evaluated by the subprotocol chair

Sites / Locations

  • ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (GSK2636771)

Arm Description

Patients receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

Secondary Outcome Measures

Overall survival (OS)
OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
Progression free survival (PFS)
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

Full Information

First Posted
June 18, 2020
Last Updated
June 6, 2023
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04439188
Brief Title
Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Loss of Expression (MATCH-Subprotocol P)
Official Title
MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Loss by IHC
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 25, 2016 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a complete loss of PTEN expression. GSK2636771 may block a protein called PI3K-beta, which may be needed for growth of cancer cells with complete loss of PTEN expression. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop its growth.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: Patients receive PI3K-beta inhibitor GSK2636771 (GSK2636771) orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (GSK2636771)
Arm Type
Experimental
Arm Description
Patients receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
PI3K-beta Inhibitor GSK2636771
Other Intervention Name(s)
GSK-2636771, GSK2636771
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
Time Frame
Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
Time Frame
Assessed every 3 months for =< 2 years and every 6 months for year 3
Title
Progression free survival (PFS)
Description
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.
Time Frame
Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) Patients must have complete loss of cytoplasmic and nuclear PTEN staining on immunohistochemistry as determined by the MATCH PTEN immunohistochemistry (IHC) assay performed at MD Anderson. Patients can have any PTEN mutation or deletion status, but MUST have PTEN loss by IHC Patients must have hemoglobin >= 9 g/dL Patients must have a serum creatinine that is < 1.5 x upper limit of normal (ULN) or have a 24-hour creatinine clearance of > 50 mL/min Exclusion Criteria: Patients must not have known hypersensitivity to GSK2636771 or compounds of similar chemical or biologic composition Patients must not have tumors harboring co-existing aberrations activating the PI3K/MTOR and MAPK pathways, such as PIK3CA, PIK3R1, BRAF, KRAS and AKT1, TSC1/2, mTOR, NF2, NRAS, HRAS, NF1 Patients must not have received prior treatment with agents targeting the PI3K beta, AKT, or mTOR: This includes (but is not limited to): mTOR inhibitors: temsirolimus, everolimus, ridaforolimus, sirolimus, salirasib, CC-223, INK128, DS-3078, CC-115, AZD-2014 Dual PI3K/mTOR inhibitors: BEZ235, XL-765, GDC 0980, PF-04691502, GSK 2126458, Quinacrine, PKI-587, P-P7170, LY3023414, GDC 0084, DS 7423, CBLC-137 Pan-PI3K inhibitors: BKM-120 (buparlisib), PX-866, XL-147, GDC-0941 (pictilisib), BAY-806946, ZSTK-474, WX 037, SRX5000, SRX2523, AMG511, PQR308, BAY 94-9343 PI3K inhibitors with beta isoform activity: prior GSK2636771 is not allowed, nor is GS-9820, PQR3XX, KAR4139 The following previous treatments are allowed: BYL719 (PI3Kalpha inhibitor) GDC-0032 (PI3Kalpha inhibitor) INK1117 (PI3Kalpha inhibitor) Idelalisib (PI3Kdelta inhibitor) IPI-125 (PI3K gamma delta inhibitor) TGR1202 (PI3Kdelta inhibitor) SRX2558 (PI3Kdelta inhibitor) RP6530 (PI3K gamma delta inhibitor) PWT143 (PI3Kdelta inhibitor) IPI443 (PI3K gamma delta inhibitor) GNE293 (PI3Kdelta inhibitor) Patients with a history of interstitial lung disease or pneumonitis are excluded Patients must not have any congenital platelet function defects and cannot be on any of the following anti-platelet drugs: clopidogrel, ticlopidine, prasugrel, that act at platelet purinergic receptors Any need for starting anti-platelet therapy in a patient enrolled to this arm will have to be evaluated by the subprotocol chair
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filip Janku
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
ECOG-ACRIN Cancer Research Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Loss of Expression (MATCH-Subprotocol P)

We'll reach out to this number within 24 hrs