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ML29255 Neoadjuvant Vemurafenib and Cobimetinib 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. Identifier: NCT03005639
Recruitment Status : Withdrawn (Sponsor has decided to close study.)
First Posted : December 29, 2016
Last Update Posted : May 9, 2018
Genentech, Inc.
Information provided by (Responsible Party):
Inova Health Care Services

Brief Summary:

Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma

• To evaluate the overall radiological complete response rate in patients with stage IIIB/C melanoma after 8 weeks of neoadjuvant vemurafenib and cobimetinib

Condition or disease Intervention/treatment Phase
Stage IIIB-C Melanoma Drug: Vemurafenib and Cobimetinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma
Actual Study Start Date : June 1, 2017
Actual Primary Completion Date : February 24, 2018
Actual Study Completion Date : February 24, 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Vemurafenib/Cobimetinib
Vemurafenib and cobimetinib as a combination has been approved by the United States Food and Drug Administration (FDA) for patients with more advanced melanoma. In this trial, vemurafenib and cobimetinib combination is considered to be experimental since safety of this combination prior to lymph node surgery has not been studied.
Drug: Vemurafenib and Cobimetinib
All participants will receive study treatment for up to 56 days (8 weeks). After completing treatment, they will undergo a lymph node removal surgery. After surgery, they will have follow-up visit 2-4 weeks after surgery.
Other Name: Zelboraf for vemurafenib

Primary Outcome Measures :
  1. Radiologic Complete Response Rate [ Time Frame: Day 56 (+/- 3 days) ]
    Radiologic complete response rate will be the primary endpoint. This will be assessed after completion of the 8-week treatment of vemurafenib and cobimetinib by CT measurements of tumor diameter pre-treatment and at day 56 (± 3 days) using RECIST 1.1. Complete response (CR) is defined by a reduction in the short-axis diameter of any pathologic lymph node to less than 10 mm, whereas partial response (PR) is defined as 30% or more decrease in the short axis. The analysis of response rate is based on the efficacy evaluable patients who has post-treatment CT scan at Day 43. Patients who discontinued study drug or withdraw from the study will be included only if they had post-treatment CT scan. We will calculate radiologic complete response rate with 95% confidence interval.

Secondary Outcome Measures :
  1. Overall response rate, pathologic complete response rate [ Time Frame: Day 56 (+/- 3 days) ]
    Overall response rate is defined as the proportion of the patients in the analysis population who have a CR or PR. Pathologic complete response is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of all sampled lymph nodes +/- primary melanoma specimen following completion of neoadjuvant systemic therapy (ypT0ypN0 in the current AJCC staging system). The analysis of pathologic response is based on the efficacy evaluable patients who underwent therapeutic lymph node dissection. Patients who discontinued study drug or withdraw from the study will be included only if they underwent therapeutic lymph node dissection. We will calculate the pathological complete response rate with 95% confidence interval.

Information from the National Library of Medicine

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

Patients will be included in the study based on the following criteria:

  • Signed informed consent
  • Histologically confirmed, palpable, regional lymph node metastatic melanoma ≥ 1.5cm (stage IIIB-C; N1b-3) either at initial presentation or at regional lymph node recurrence considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist
  • Patients with intransit or satellite metastases with lymph node involvement are allowed if considered surgically resectable at baseline
  • Measurable disease per RECIST 1.1
  • Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory
  • No evidence of distant metastasis
  • Age ≥ 18 years
  • ECOG performance status ≤1
  • Adequate bone marrow function as indicated by the following:

    • ANC greater than 1500/µL
    • Platelets ≥ 100,000/µL
    • Hemoglobin greater than 9 g/dL
  • Adequate renal function, as indicated by creatinine ≤1.5 x the upper limit of normal (ULN)
  • Adequate liver function, as indicated by bilirubin ≤1.5 x ULN
  • AST or ALT less than 3 x ULN (patients with documented liver metastases: AST and/or ALT ≤5 x ULN)
  • Able to swallow pills
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
  • Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Willing and able to undergo biopsy for research purposes
  • Willing and able to sign informed consent

Exclusion Criteria:

  • Had prior radiotherapy at lymph node basin
  • Prior treatment with BRAF inhibitor or MEK inhibitor
  • Active infection
  • Pregnant, lactating or breast feeding women
  • Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • History of malabsorption or other condition that would interfere with absorption of vemurafenib or cobimetinib
  • Any underlying medical or psychiatric condition, which in the opinion of the Investigator will make the administration of vemurafenib and cobimetinib hazardous
  • Unwillingness or inability to comply with study and follow-up procedures.
  • The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:

    • St. John's 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 identifier (NCT number): NCT03005639

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United States, Virginia
Inova Schar Cancer Institute
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Inova Health Care Services
Genentech, Inc.
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Principal Investigator: Sekwon Jang, MD Inova Schar Cancer Institute
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Responsible Party: Inova Health Care Services Identifier: NCT03005639    
Other Study ID Numbers: 16-2316
First Posted: December 29, 2016    Key Record Dates
Last Update Posted: May 9, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action