Stage IIIB-C Melanoma Clinical Trial
Official title:
Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma
| Verified date | May 2018 |
| Source | Inova Health Care Services |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | February 24, 2018 |
| Est. primary completion date | February 24, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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) |
| Country | Name | City | State |
|---|---|---|---|
| United States | Inova Schar Cancer Institute | Fairfax | Virginia |
| Lead Sponsor | Collaborator |
|---|---|
| Inova Health Care Services | Genentech, Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Radiologic Complete Response Rate | 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. | Day 56 (+/- 3 days) | |
| Secondary | Overall response rate, pathologic complete response rate | 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. | Day 56 (+/- 3 days) |