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

• 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 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.

• 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 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