- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04439188
Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Loss of Expression (MATCH-Subprotocol P)
MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Loss by IHC
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19103
- ECOG-ACRIN Cancer Research Group
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (GSK2636771)
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.
|
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (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
|
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.
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Assessed every 3 months for =< 2 years and every 6 months for year 3
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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.
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Assessed every 3 months for =< 2 years and every 6 months for year 3
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Progression free survival (PFS)
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
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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.
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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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Filip Janku, ECOG-ACRIN Cancer Research Group
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Neoplasms
- Lymphoma
- Multiple Myeloma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- GSK2636771
Other Study ID Numbers
- NCI-2020-03143 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180820 (U.S. NIH Grant/Contract)
- U24CA196172 (U.S. NIH Grant/Contract)
- EAY131-P (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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