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

Purpose

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.

Condition	Intervention	Phase
Malignant Melanoma	Drug: vemurafenib Drug: Placebo Drug: GDC-0973	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	A PHASE III, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF VEMURAFENIB VERSUS VEMURAFENIB PLUS GDC-0973 IN PREVIOUSLY UNTREATED BRAFV600-MUTATION POSITIVE PATIENTS WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC MELANOMA

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Vemurafenib

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Progression-free survival according to Response Evaluation Criteria in Solid Tumors v1.1 [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Objective response rate according to Response Evaluation Criteria in Solid Tumors v1.1 [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Duration of response according to Response Evaluation Criteria in Solid Tumors v1.1 [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Safety: incidence of adverse events [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Pharmacokinetics: Area under the plasma concentration time curve trough 24 hours [ Time Frame: Cycle 1, days 1 and 15; cycle 2, day 15 ] [ Designated as safety issue: No ]
Pharmacokinetics: Minimum observed plasma concentration [ Time Frame: Cycle 1, days 1 and 15; cycle 2, day 15 ] [ Designated as safety issue: No ]
Pharmacokinetics: Apparent clearance following oral dosing [ Time Frame: Cycle 1, days 1 and 15; cycle 2, day 15 ] [ Designated as safety issue: No ]
Quality of life as measured by the European Organization for Research and Cancer Quality of Life Questionnaire (QLQ-30) [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Quality of life as measured by the EuroQol 5 dimension (EQ-5D) [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	500
Study Start Date:	January 2013
Estimated Study Completion Date:	August 2016
Estimated Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Control Arm	Drug: vemurafenib 960 mg orally twice a day on days 1-28 of each 28-day cycle. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent Drug: Placebo Placebo orally once a day on days 1-21 of each 28-day treatment cycle. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent
Experimental: Investigational Arm	Drug: vemurafenib 960 mg orally twice a day on days 1-28 of each 28-day cycle. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent Drug: GDC-0973 60 mg orally once a day on days 1-21 of each 28-day treatment cycle. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01689519

Contacts

Contact: Reference Study ID Number: GO28141 www.roche.com/about_roche/roche_worldwide.htm

888-662-6728 (U.S. Only)

global.rochegenentechtrials@roche.com

Show 194 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01689519 History of Changes
Other Study ID Numbers:	GO28141, 2012-003008-11
Study First Received:	September 18, 2012
Last Updated:	May 23, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hoffmann-La Roche:

BRAF positive melanoma
Genentech BRAF inhibitor
vemurafenib
RG7204
Roche MEK inhibitor
Oncogenic BRAF inhibitor
metastatic melanoma
advanced melanoma
GDC-0973
PLX4032
Genentech RAF inhibitor

melanoma
Roche BRAF inhibitor
Genentech MEK inhibitor
RO5185426
XL518
Zelboraf
BRAF V600E kinase inhibitor
Roche RAF inhibitor
BRAF kinase inhibitor
BRAF mutant melanoma

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 23, 2013