ML29255 Neoadjuvant Vemurafenib and Cobimetinib Melanoma

NCT ID: NCT03005639

Last Updated: 2018-05-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2018-02-24

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

Detailed Description

Vemurafenib and cobimetinib are FDA-approved drugs to treat advanced melanoma that has a mutated (changed) form of a cell protein called BRAF (BRAF V600 mutation). The purpose of this study is to determine if vemurafenib and cobimetinib can be safely given to patients with this type of melanoma to shrink it before surgery. This research is being done because patients with melanoma spread to lymph node have high chance of melanoma recurrence even after lymph node removal surgery, and currently there is no approved medicine to use for patients with BRAF V600 mutant melanoma before lymph node removal surgery.

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.

Before the participant begins the study:

The participant will need to have the following exams, tests or procedures to find out if eligibility is met.

• A skin exam
• An eye exam
• An electrocardiogram (ECG) which is a test that tracks the electricity of the heart
• An echocardiogram (a test that uses sound waves to create pictures of the heart) or MUGA scan (a test that uses radioactive materials called tracers to show the heart chambers) which is a test to evaluate the function of the heart
• A blood test
• A biopsy of lymph node

If the exams and tests listed above show that the individual can take part in the study, and he or she chooses to take part, then the participant will take the study drugs for 8weeks. He/she will take vemurafenib 240mg 4tablets twice daily for 56days and cobimetinib 20mg 3 tablets daily on days 1-21 and 29-49. While taking these pills, the following extra exams and tests will be needed.

• Four extra blood samples will be drawn. One blood sample will be drawn immediately before the first dose of the vemurafenib and trametinib pills. Then blood sample will be drawn 2 weeks, 4weeks, and 8weeks after starting the pills.
• A biopsy of lymph node will be performed 2weeks after starting the pills.
• Skin exams will be performed immediately before the first dose, 2weeks, 4weeks, and 8weeks after starting the pills.
• Eye exams will be performed 4weeks, 8weeks after starting the pills.
• An ECG will be performed 2weeks, 4weeks, and 8weeks after starting the pills.
• An echocardiogram or MUGA scan will be performed 4weeks after starting the pills.
• A CT scan will be performed 8weeks after starting the pills.

Once the participant finishes 8weeks of study drugs, he or she will undergo surgery within a week. After surgery, the individual will need the following extra exam.

• A skin exam A blood sample will be taken for the study at the first study visit, two week visit and eight week visit. Tissue from a core biopsy will be taken for the study at the first study visit and two week visit. This sample is required in order for the individual to take part in this study because the research on the sample is an important part of the study. The research biopsy is done in a similar way to biopsies done for diagnosis. Neither the participant nor the participant's health care plan/insurance carrier will be billed for the collection of the blood and tissue sample that will be used for this study. The results will not be made available to the participant during participation in the trial.

Conditions

Stage IIIB-C Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vemurafenib and Cobimetinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Zelboraf for vemurafenib

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Inova Health Care Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sekwon Jang, MD

Role: PRINCIPAL_INVESTIGATOR

Inova Schar Cancer Institute

Locations

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Countries

United States

Other Identifiers

16-2316

Identifier Type: -

Identifier Source: org_study_id