Clinical Trial to Evaluate the Efficacy of Vemurafenib in Combination With Cobimetinib (Continuous and Intermittent) in BRAFV600-mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma

NCT02583516 | Completed Phase 2

• 2 other identifiers: GEM-01-152014-005277-36
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 18

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of two different schedules of administration of vemurafenib in combination with cobimetinib (continuous and intermittent) in previously untreated BRAFV600- mutation positive patients with unresectable locally advanced or metastatic melanoma.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Through study completion, up to 42 months

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Through study completion, up to 42 months

• Progression Free Survival (PFS) at one and two years

  At one and two years

• Overall Survival (OS) at one and two years

  At one and two years

• Adverse Events (AE) occurrence

  Through study completion, up to 42 months

• Serious Adverse Events (SAE) occurrence

  Through study completion, up to 42 months

Other Outcomes (3)

• BRAF mutation determination (Translational sub-study)

  Through study completion, up to 42 months

• Analysis of resistance mechanisms to the combination of vemurafenib and cobimetinib (Translational sub-study)

  Through study completion, up to 42 months

• Analysis of disease's resistance mechanisms (Translational sub-study)

  Through study completion, up to 42 months

Study Arms (2)

A - Continuous Administration

EXPERIMENTAL

960 mg of vemurafenib po, bid, days 1 to 28 and 60 mg of cobimetinib po, od, days 1 to 21, for each 28-days' cycle.

Drug: vemurafenib and cobimetinib

B - Intermittent Administration

EXPERIMENTAL

960 mg of vemurafenib po, bid, days 1 to 28 and 60 mg of cobimetinib po, od, days 1 to 21, for each 28-days' cycle, during 12 weeks. After that period, patients will be treated with both drugs at the same doses indicated previously, but with an intermittent pattern: vemurafenib days 1 to 28 followed by 14 days off (4 weeks on and 2 weeks off) and cobimetinib days 1 to 21 followed by 21 days off (3 weeks on and 3 weeks off)

Drug: vemurafenib and cobimetinib

Interventions

vemurafenib and cobimetinib DRUG

Comparison between different treatment regimens

A - Continuous Administration; B - Intermittent Administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma.
• Patients must be naïve to treatment for locally advanced unresectable or metastatic disease.
• Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue.
• Measurable disease per RECIST v1.1.
• ECOG performance status of 0 or 1.
• Additionally, patients to be included in the biomarker sub- study should meet the following criteria:
• Consent to provide archival tissue for biomarker analyses.
• Consent to undergo tumor biopsies.
• Male or female patient aged major or equal 18 years.
• Able to participate and willing to give written informed.
• Life expectancy mayor o igual 12 weeks.
• Adequate hematologic and end organ function, within 14 days prior to first dose of study drug treatment:
• ANC major or equal 1.5 × 109/L.
• Platelet count major or equal 100 × 109/L.
• Hemoglobin major or equal 9 g/dL.

You may not qualify if:

• 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 BCC or SCC of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast. History of isolated elevation in prostate-specific antigen in the absence of radiographic evidence of metastatic prostate cancer is allowed.
• 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.
• The risk factors for RVO are listed below. Patients will be excluded if they have the following conditions:
• Uncontrolled glaucoma with intra-ocular pressures \> 21 mmHg.
• Serum cholesterol major or equal Grade 2.
• Hypertriglyceridemia major or equal Grade 2.
• Hyperglycemia (fasting) major or equal Grade 2.
• History of clinically significant cardiac dysfunction, including the following:
• Current unstable angina.
• Symptomatic congestive heart failure of New York Heart Association class 2 or higher.
• History of congenital long QT syndrome or mean (average of triplicate measurements) QTcF \> 450 msec at baseline or uncorrectable abnormalities in serum electrolytes (sodium, potassium, calcium, magnesium, phosphorus). If not automated, calculation of QTcF must be done through the following formula: QTcF = (QT interval in ms) / \[(60 / heart rate in bpm) )\^(1/3)\]
• Uncontrolled hypertension major or equal Grade 2 (patients with a history hypertension controlled with anti-hypertensives to minor or equal Grade 1 are eligible).

Sponsors & Collaborators

• Grupo Español Multidisciplinar de Melanoma: lead
• Roche Farma, S.A: collaborator
• Pivotal S.L.: collaborator

Study Sites (18)

Hospital Universitario Donostia

Donostia / San Sebastian, Guipuzcoa, Spain

Location

Hospital General Universitario Santa Lucía

Cartagena, Murcia, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Insular de Gran Canaria

Las Palmas de Gran Canaria, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

Hospital Universitario Doctor Peset

Valencia, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Hospital Álvaro Cunqueiro (Complejo Hospitalario Universitario de Vigo)

Vigo, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

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Related Links

• Spanish Multidisciplinary Melanoma Group Web

MeSH Terms

Conditions

Melanoma

Interventions

Vemurafenib; cobimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• José Antonio López-Martín, MD, PhD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

• Alfonso Berrocal, MD, PhD

  Hospital General Universitario de Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 22, 2015
• Study Start: June 30, 2015
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: February 17, 2020

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (18)