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

• Status: Active, not recruiting
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: GSK2636771

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