Phase Ib Trial of AEB071, a PKC Inhibitor, in Combination with BYL719, a PI3Kα? Inhibitor, in Patients with Metastatic Uveal Melanoma

Protocol: 
AAAN4901
Phase: 
I

Phase Ib Trial of AEB071, a PKC Inhibitor, in Combination with BYL719, a PI3Kα? Inhibitor, in Patients with Metastatic Uveal Melanoma

This Phase 1B study is for individuals with advanced uveal melanoma that is growing. There are no approved drugs for uveal melanoma, so there is no single standard treatment approach. Traditional chemotherapy does not work well for most people with advanced uveal melanoma. Because of this, the usual approach is to recommend taking part in a clinical trial, such as this one, where newer medicines are being tested. Uveal melanoma cells have specific growth signals that are “turned on” abnormally. In the past few years, studies have shown some benefit to giving newer drugs that specifically block certain growth signals. This study uses a combination of drugs, AEB071 and BYL719, which block two signals that tell uveal melanoma cells to grow. AEB071 has been given safely on its own to people with advanced uveal melanoma. BYL719 has been given safely on its own to patients with other types of cancer. The purpose of this study is to test whether it is safe to give AEB071 and BYL719 together. This study has two parts. The first part will test different dose levels of each drug. About 4 to 30 people will participate in this first part of the study. Once the highest safe dose level is found, another 20 people will be treated at that dose.

Are you Eligible? (Inclusion Criteria)

1) Patients must be at least 18 years old.
2) Metastatic histologically or cytologically confirmed uveal melanoma with
pathologic confirmation at a participating center that is judged to be progressive in the opinion of the treating physician. For the dose escalation portion of the trial only, patients with non-uveal melanoma harboring a GNAQ or GNA11 mutation will also be eligible.
3) Prior cytotoxic therapy and immunotherapy are allowed. For the dose escalation, prior targeted therapy with a MEK inhibitor, Protein Kinase C inhibitor, Akt, or mTOR inhibitor are allowed. For the dose expansion cohort, no prior PKC, Akt, or mTOR inhibitors are allowed, and registration is limited to 10 patients who are MEK inhibitor-naïve and 10 patients who are MEKi resistant. Local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least 21 days prior to initiation of study therapy. Lesions treated with local or regional modalities such as radiofrequency ablation, or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging studies.

Exclusion Criteria:
1) Patients cannot have a history of another malignancy except for those who have been disease free for 24 months.
2) Any major surgery or extensive radiotherapy within 28 days prior to screening.
3) Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression. Treated brain metastases must have been stable for at least 1 month.

Specialty Area(s)

Trial Location

Herbert Irving Comprehensive Cancer Center
161 Fort Washington Ave.
Herbert Irving Pavilion
New York, NY 10032
United States