Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss

Metastatic Melanoma Clinical Trial

Official title: Phase I/II Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss

Status Active, not recruiting

Clinical Trial Summary

The goal of this clinical research study is to learn if GSK2636771 given in combination with pembrolizumab can help to control the disease in patients with refractory (has not responded to treatment) metastatic melanoma. The safety of this drug combination will also be studied.

This is an investigational study. Pembrolizumab is FDA approved and commercially available and FDA approved for the treatment of several types of cancer, including melanoma. GSK2636771 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work.

Up to 41 participants will be enrolled in this study. All will take part at MD Anderson.

Clinical Trial Description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of 3-6 participants will be enrolled in Phase 1 of the study, and up to 35 participants will be enrolled in Phase 2.

If you have metastatic cancer, you may be enrolled in Phase 1 of this study. If you have metastatic melanoma, you may be enrolled in Phase 1 or Phase 2 of this study.

If you are enrolled in Phase 1, the dose of GSK2636771 in combination with pembrolizumab you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of GSK2636771. Each new group will receive a higher dose of GSK2636771 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of GSK2636771 is found.

If you are enrolled in Phase 2, you will receive GSK2636771 at the highest dose that was tolerated in Phase 1.

All participants will receive the same dose level of pembrolizumab.

Study Drug Administration:

Every study cycle is 21 days.

• You will take GSK2636771 by mouth every day for 21 days.

• You will receive pembrolizumab by vein for 30 minutes one (1) time on Day 1 of every cycle.

You should receive the study drugs at least 1 hour before or 2 hours after eating.

Length of Study:

You may receive the study drugs for up to 2 years. If the doctor thinks it is in your best interest, you may continue to receive either GSK2636771 or pembrolizumab for 1 more year. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the Follow-Up Visits.

Study Visits:

On Day 1 of Cycles 1, 3, 5, and 7:

• You will have a physical exam.

• You will have an EKG. If the doctor thinks it is needed, you will also have an ECHO and MUGA scan.

• Blood (about 3 teaspoons) and urine will be collected for routine tests.

• Blood (about 2 tablespoons) will be drawn for pharmacokinetic (PK) testing before the dose, at 30 minutes, 1, 2, 3, 4, 6, and 24 hours after the dose. (Cycle 1 only). PK testing measures the amount of study drug in the body at different time points.

• Blood (about 2 tablespoons) will be drawn for immune function testing (Cycles 3 & 5 only).

• You will have a PET/CT scan or MRI to check the status of the disease (Cycle 5 only and then every 12 weeks after that).

• If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycles 2, 4, 6, 8 and beyond:

• You will have a physical exam.

• Blood (about 1½ teaspoon) and urine will be collected for routine tests.

• Blood (about 1 teaspoon) will be drawn for PK testing before the dose. (Cycle 2 only)

• If the doctor thinks it is needed, you will have an ECHO and MUGA scan.

• If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycles 2, 3, and 5, and every 12 weeks after that, you will be asked to have a core biopsy. Only 1 of these will be required, and the others will be optional. Though it is preferred that this be performed at Cycle 2, you and your doctor will choose which of these biopsies will be the required one.

Every 12 weeks after Cycle 5, blood (about 2½ tablespoons) will be drawn for immune system testing.

End of Study Dosing Visit:

After you stop receiving the study drugs:

• You will have a physical exam.

• If the doctor thinks it is needed, you will have an ECHO and MUGA scan.

• Blood (about 1 teaspoon) and urine will be collected for routine tests.

• If the disease got worse while you are on study, you may have a core biopsy.

• If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

Follow-Up Period:

Up to 30 days after the End-of-Study Dosing Visit and every 6 weeks:

• You will have a physical exam.

• Blood (about 2 tablespoons) and urine will be collected for routine tests.

• If the doctor thinks it is needed, you will have an ECHO and MUGA scan.

• If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

One (1) time every 12 weeks:

• You will have a PET/CT) scan or MRI to check the status of the disease.

• You will be called by a member of the study staff to check your health. These calls should last about 5 minutes each time.

Treatment Beyond Progression:

If the disease appears to be getting worse or the tumors appear to be getting larger, you may still be able to receive the study drug if you and your doctor decide it is in your best interest. Sometimes the disease appears to get worse but the study drug is actually working.

However, there are risks of continuing to receive the study drug because the disease may actually be getting worse. You are still at risk for side effects due to the study drug. This could also delay starting other treatments. The disease may get worse to the point that you are no longer able to receive other treatments.

If you choose to receive the study drug after the disease gets worse, you will continue to have study visits. The study doctor will discuss this option with you.

Alcohol and Activity Restriction:

On days when you have multiple PK blood draws, you should not have alcohol for at least 24 hours before your dose of study drug.

You should not exercise for 48 hours before each PK and/or routine testing blood draw. ;

Related Conditions & MeSH terms

• Melanoma
• Melanoma and Other Malignant Neoplasms of Skin
• Metastatic Melanoma
• Neoplasms
• Skin Neoplasms

• NCT number: NCT03131908
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 17, 2017
• Completion date: December 31, 2025