Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Genetic Changes (MATCH-Subprotocol N)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT04439149

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a genetic change called PTEN mutation or deletion. GSK2636771 may block a protein called PI3K-beta, which may be needed for growth of cancer cells that express PTEN mutations. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop its growth.

Condition or Disease	Intervention/Treatment	Phase
Advanced Lymphoma Advanced Malignant Solid Neoplasm Hematopoietic and Lymphoid Cell Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Plasma Cell Myeloma	Drug: PI3K-beta Inhibitor GSK2636771	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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.
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.
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 Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

MATCH Treatment Subprotocol N: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Mutation or Deletion, With PTEN Expression on IHC

Actual Study Start Date :

Feb 25, 2016

Anticipated Primary Completion Date :

Nov 30, 2022

Arms and Interventions

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.	Drug: PI3K-beta Inhibitor GSK2636771 Given PO Other Names: GSK-2636771 GSK2636771

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.

Drug: PI3K-beta Inhibitor GSK2636771

Given PO

Other Names:

GSK-2636771

GSK2636771

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [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.

Secondary Outcome Measures

Overall survival (OS) [Assessed every 3 months for =< 2 years and every 6 months for year 3]
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 w ill be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
Progression free survival (PFS) [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]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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 PTEN gene mutation/deletion
There must be evidence of PTEN expression by immunohistochemistry (IHC) (any amount of staining will be considered positive for expression)
Patients with complete loss of PTEN by IHC, regardless of PTEN mutations/deletion status, will be enrolled into MATCH subprotocol EAY131-P, not this subprotocol (EAY131-N)
Patients must have hemoglobin >= 9 g/dL
Patients must have a serum creatinine that =< 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 pathways:

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 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