Study of Neo-adjuvant Use of Vemurafenib Plus Cobimetinib for BRAF Mutant Melanoma With Palpable Lymph Node Metastases

NCT02036086 | Unknown Phase 2

• 1 other identifier: ML28606
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the clinical and pathological response to vemurafenib and cobimetinib in the neoadjuvant treatment of patients with histologically confirmed, BRAF V600 mutation-positive Stage IIIB and C melanoma. 20 patients will be treated with vemurafenib and cobimetinib for 2 months. Then they will be assessed for surgery. Patients will undergo surgery and subsequently resume taking vemurafenib and cobimetinib after recovery from surgery. Patients will undergo radiation therapy if appropriate then continue vemurafenib and cobimetinib. The maximum treatment period is 12 months. After 12 months of treatment, patients will be followed for disease recurrence and survival during for a total of 5 years.

Conditions

Melanoma

Keywords

Melanoma stage IIIB or C with BRAF mutation; Recurrent regional lymphadenopathy not suitable for surgery; Eligible for neoadjuvant vemurafenib and cobimetinib

Outcome Measures

Primary Outcomes (1)

• The feasibility of treating patients with unresectable melanoma and palpable lymph node metastases that harbor the BRAF mutation with neoadjuvant vemurafenib.

  24 months

Secondary Outcomes (6)

• Resectability rates post vemurafenib therapy

  5 years

• Local-regional recurrence rates after treatment with neo-adjuvant vemurafenib.

  5 years

• Time to distant metastases and Distant Metastatic Free Survival (DMFS).

  5 years

• Disease Free Survival (DFS) and Overall Survival (OS).

  5 years

• Immunohistochemical correlates of tumor response.

  5 years

Study Arms (1)

Vemurafenib, pill, twice daily

EXPERIMENTAL

Vemurafenib, 960 mg, oral, twice daily plus Cobimetinib, 60 mg, oral, four times daily

Drug: Vemurafenib; Drug: Cobimetinib

Interventions

Vemurafenib DRUG

Drug

Also known as: Zelboraf

Vemurafenib, pill, twice daily

Cobimetinib DRUG

Drug

Also known as: GDC-0973

Vemurafenib, pill, twice daily

Eligibility Criteria

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

You may qualify if:

• Naïve to treatment for locally advanced unresectable disease (Stage IIIB and C). Prior adjuvant therapy (including immunotherapy, e.g., ipilimumab) is allowed if prior to nodal recurrence and ≥ 3 months have elapsed from the last day of adjuvant therapy to start of study treatment.
• Biopsy proven unresected melanoma patients with palpable regional lymph node metastases, presenting with AJCC stage IIIB-C or with recurrent regional lymphadenopathy that are not suitable or not preferred for surgical intervention.
• BRAF V600 mutation positive.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Adequate hematologic, renal and liver function within 7 days prior to the first dose of vemurafenib and cobimetinib.
• Agree to always use an effective form(s) of contraception beginning from the informed consent signature date until at least 6 months after completion of study therapy.
• Negative serum pregnancy test within 14 days prior to start of treatment in women of childbearing potential only.
• Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

You may not qualify if:

• Cannot have received any prior therapy for the current recurrence or nodal disease. Previous adjuvant immunotherapy is allowed if prior to nodal recurrence and ≥ 3 months have elapsed from the last day of adjuvant therapy to start of study treatment.
• History of prior RAF or MEK pathway inhibitor treatment.
• Active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years are excluded; except for patients with resected melanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected melanoma in situ, resected carcinoma in-situ of the cervix, and resected carcinoma in-situ of the breast.
• Evidence of distant metastatic disease.
• History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or known infection with Human Immunodeficiency Virus (HIV), hepatitis B virus, or hepatitis C virus.
• Active infection or chronic infection requiring chronic suppressive antibiotics.
• Pregnant or breastfeeding at the time of enrollment.
• Active autoimmune disease (e.g., systemic lupus erythematosus, autoimmune vasculitis, inflammatory bowel disease \[Crohn's disease and ulcerative colitis\]).
• Acromegaly
• History of malabsorption or other clinically significant metabolic dysfunction.
• Any other serious concomitant medical condition that would compromise safety or compromise the ability to participate in the study.
• Requires a concomitant medication or dietary supplement that is prohibited during the study.
• Unwillingness or inability to comply with study and follow-up procedures.
• Current, recent (within 28 days of enrolment) or planned use of any investigational product outside of this study.
• The following foods or supplements are prohibited at least 7 days prior to initiation of and during study treatment:

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (3)

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Related Publications (16)

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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

• Teresa Petrella, MD, BSc, MSc

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 28, 2013
• First Posted: January 14, 2014
• Study Start: August 1, 2015
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: October 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

CA (3)