Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    21107320 [PUBMED-IDS]
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02583516
Recruitment Status : Active, not recruiting
First Posted : October 22, 2015
Last Update Posted : July 31, 2019
Sponsor:
Collaborators:
Roche Farma, S.A
Pivotal S.L.
Information provided by (Responsible Party):
Grupo Español Multidisciplinar de Melanoma

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: vemurafenib and cobimetinib Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Actual Study Start Date : June 30, 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: A - Continuous Administration
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
Comparison between different treatment regimens

Experimental: B - Intermittent Administration
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
Comparison between different treatment regimens




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Through study completion, up to 42 months ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Through study completion, up to 42 months ]
  2. Progression Free Survival (PFS) at one and two years [ Time Frame: At one and two years ]
  3. Overall Survival (OS) at one and two years [ Time Frame: At one and two years ]
  4. Adverse Events (AE) occurrence [ Time Frame: Through study completion, up to 42 months ]
  5. Serious Adverse Events (SAE) occurrence [ Time Frame: Through study completion, up to 42 months ]
  6. Adverse Events of Special Interest (AESI) occurrence [ Time Frame: Through study completion, up to 42 months ]

Other Outcome Measures:
  1. BRAF mutation determination (Translational sub-study) [ Time Frame: Through study completion, up to 42 months ]
    Analysis of prognostic and predictive value of BRAF mutation in cell-free DNA (cfDNA) samples, and its role in disease evolution monitoring.

  2. Analysis of resistance mechanisms to the combination of vemurafenib and cobimetinib (Translational sub-study) [ Time Frame: Through study completion, up to 42 months ]
    Non-invasive monitorization of resistance mechanisms, through selected gene expression cuantification from blood mRNA.

  3. Analysis of disease's resistance mechanisms (Translational sub-study) [ Time Frame: Through study completion, up to 42 months ]
    Determination of resistance mechanisms in secuential biopsies of the disease.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Disease-Specific Inclusion Criteria:

  1. Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma.
  2. Patients must be naïve to treatment for locally advanced unresectable or metastatic disease.
  3. Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue.
  4. Measurable disease per RECIST v1.1.
  5. ECOG performance status of 0 or 1.
  6. 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.

    General Inclusion Criteria:

  7. Male or female patient aged major or equal 18 years.
  8. Able to participate and willing to give written informed.
  9. Life expectancy mayor o igual 12 weeks.
  10. 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.
    • Albumin major or equal 2.5 g/dL.
    • Bilirubin minor or equal 1.5 × the upper limit of normal (ULN).
    • AST, ALT, and alkaline phosphatase minor or equal 3 × ULN, with the following exceptions:
    • Patients with documented liver metastases: AST and/or ALT minor or equal 5 × ULN.
    • Patients with documented liver or bone metastases alkaline phosphatase minor o equal 5 × ULN.
    • Serum creatinine minor o equal 1.5 × ULN or CrCl major or equal 40 mL/min on the basis of measured CrCl from a 24- hour urine collection.
  11. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use 2 effective forms of contraception during the course of this study and for at least 6 months after completion of study therapy.
  12. Negative serum pregnancy test within 10 days prior to commencement of dosing in women of childbearing potential.
  13. Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol and follow-up after treatment discontinuation schedule.

Exclusion Criteria:

Cancer-Related Exclusion Criteria:

  1. History of prior RAF or MEK pathway inhibitor treatment.
  2. Palliative radiotherapy within 14 days prior to the first dose of study treatment.
  3. Major surgery or traumatic injury within 14 days prior to first dose of study treatment.
  4. 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.

    Exclusion Criteria Based on Ocular Function:

  5. 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.

    Exclusion Criteria Based on Cardiac Function:

  6. 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).
    • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%.

    Exclusion Criteria Based on Central Nervous System Function:

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

    • All known CNS lesions have been treated with stereotactic therapy or surgery, AND
    • There has been no evidence of clinical and radiographic disease progression in the CNS for major or equal 3 weeks after radiotherapy or surgery.

    Whole brain radiotherapy is not allowed, with the exception of patients who have had definitive resection or stereotactic therapy of all radiologically detectable parenchymal brain lesions.

    General Exclusion Criteria:

  8. Current severe, uncontrolled systemic disease.
  9. History of malabsorption or other condition that would interfere with absorption of study drugs.
  10. Pregnant or lactating.
  11. Unwillingness or inability to comply with study and follow- up procedures.
  12. The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:

    • St. Johns wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer).
    • Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02583516


Locations
Layout table for location information
Spain
Hospital Universitario Donostia
Donostia - San Sebastián, Guipuzcoa, Spain
Hospital General Universitario Santa Lucía
Cartagena, Murcia, Spain
Hospital Clínic de Barcelona
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Universitario Vall d'Hebron
Barcelona, Spain
Hospital Insular de Gran Canaria
Las Palmas de Gran Canaria, Spain
Hospital Universitario Lucus Augusti
Lugo, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Regional Universitario de Málaga
Málaga, Spain
Hospital Clínico Universitario de Salamanca
Salamanca, Spain
Hospital Universitario Virgen Macarena
Sevilla, Spain
Hospital Universitario de Canarias
Tenerife, Spain
Hospital General Universitario de Valencia
Valencia, Spain
Hospital Universitario Doctor Peset
Valencia, Spain
Hospital Universitario y Politécnico La Fe
Valencia, Spain
Hospital Álvaro Cunqueiro (Complejo Hospitalario Universitario de Vigo)
Vigo, Spain
Hospital Universitario Miguel Servet
Zaragoza, Spain
Sponsors and Collaborators
Grupo Español Multidisciplinar de Melanoma
Roche Farma, S.A
Pivotal S.L.
Investigators
Layout table for investigator information
Principal Investigator: José Antonio López-Martín, MD, PhD Hospital Universitario 12 de Octubre
Principal Investigator: Alfonso Berrocal, MD, PhD Hospital General Universitario de Valencia

Additional Information:
Publications:

Layout table for additonal information
Responsible Party: Grupo Español Multidisciplinar de Melanoma
ClinicalTrials.gov Identifier: NCT02583516     History of Changes
Other Study ID Numbers: GEM-01-15
2014-005277-36 ( EudraCT Number )
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vemurafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action