Clinical Trials

A Phase 3 Study Comparing GDC-0973, a MEK Inhibitor, in Combination With Vemurafenib vs Vemurafenib Alone in Patients With Metastatic Melanoma

Location:

Rochester,  MN

Trial status:

Open for Enrollment

Why is this study being done?

This multicenter, randomized, double-blind, placebo-controlled phase 3 study will evaluate the safety and efficacy of vemurafenib alone and vemurafenib in combination with GDC-0973, a MEK inhibitor, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma. Patients will be randomized to one of two treatment arms, Arm A: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and placebo (days 1-21 of each cycle); Arm B: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and GDC-0973 60 mg once daily (days 1-21 of each cycle). Patients will receive treatment until disease progression, unacceptable toxicity or withdrawal of consent.

Who is eligible to participate?

Inclusion Criteria:

- Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition.

- Unresectability of stage IIIc disease must have confirmation from a surgical oncologist.

- Patients must be naïve to treatment for locally advanced unresectable or metastatic disease (i.e., no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed.

- Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test.

- Measurable disease per RECIST v1.1.

- Eastern Clinical Oncology Group performance status of 0 or 1.

- Consent to provide archival for biomarker analyses.

- Consent to undergo tumor biopsies for biomarker analyses.

- Life expectancy >/= 12 weeks.

- Adequate hematologic and end organ function

Exclusion Criteria:

- History of prior RAF or MEK pathway inhibitor treatment.

- Palliative radiotherapy within 14 days prior to the first dose of study treatment.

- Major surgery or traumatic injury within 14 days prior to first dose of study treatment.

- Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Patients with a previous malignancy within the past 3 years are excluded except for patients with resected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast.

- History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration.

- Uncontrolled glaucoma with intra-ocular pressures

- Serum cholesterol >/= Grade 2

- Hypertriglyceridemia >/= Grade 2

- Hyperglycemia (fasting) >/= Grade 2

- History of clinically significant cardiac dysfunction

- Patients with active CNS lesions (including carcinomatous meningitis) are excluded. However, patients are eligible if:

1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND

2. There has been no evidence of clinical and radiographic disease progression in the CNS for >/= 3 weeks after radiotherapy or surgery

- Current severe, uncontrolled systemic disease.

- History of malabsorption or other condition that would interfere with absorption of study drugs.

- Pregnant, lactating, or breast feeding.

Last updated: 05/13/2013

NCT ID:

NCT01689519