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Vemurafenib, Cobimetinib, and Atezolizumab in Treating Participants With High-Risk Stage III Melanoma

2018-06-18 02:03:11 | BioPortfolio

Summary

This early phase I pilot trial studies how well vemurafenib, cobimetinib, and atezolizumab work in treating participants with high-risk stage III melanoma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving vemurafenib, cobimetinib, and atezolizumab may work better in treating high-risk stage III melanoma.

Description

PRIMARY OBJECTIVES:

I. To estimate the percentage of patients with stage III BRAFV600 mutated (BRAFm) melanoma that achieves a pathologic complete response after 12 weeks of neoadjuvant vemurafenib/cobimetinib/atezolizumab (neoadjuvant phase).

II. To estimate the percentage of patients with stage III BRAF-wild-type (BRAFwt) melanoma that achieves a pathologic complete response after 12 weeks of neoadjuvant cobimetinib/atezolizumab (neoadjuvant phase).

III. To assess recurrence-free survival (RFS) in patients with stage III BRAFm melanoma after neoadjuvant vemurafenib/cobimetinib/ atezolizumab, surgery, and adjuvant atezolizumab (adjuvant phase).

IV. To assess RFS in patients with stage III BRAFwt melanoma after neoadjuvant cobimetinib/atezolizumab, surgery, and adjuvant atezolizumab (adjuvant phase).

SECONDARY OBJECTIVES:

I. To determine the frequency of adverse events among patients with stage III BRAFm melanoma receiving neoadjuvant vemurafenib / cobimetinib / atezolizumab followed by surgery followed by adjuvant atezolizumab.

II. To determine the frequency of adverse events among patients with stage III BRAFwt melanoma receiving neoadjuvant cobimetinib/atezolizumab followed by surgery followed by adjuvant atezolizumab.

TRANSLATIONAL OBJECTIVES:

I. To determine the association between pretreatment, on treatment, post-neoadjuvant and post-adjuvant treatment soluble PD-L1 (sPD-L1) and RFS in patients with stage III melanoma receiving neoadjuvant vemurafenib / cobimetinib / atezolizumab or cobimetinib/atezolizumab, followed by surgery and adjuvant atezolizumab.

II. To determine the association between pretreatment, on treatment, post-neoadjuvant and post-adjuvant treatment intracellular bim in tumor-related T cells and RFS in patients with stage III melanoma after neoadjuvant vemurafenib/cobimetinib/atezolizumab or cobimetinib/atezolizumab, followed by surgery and adjuvant atezolizumab.

III. Evaluate associations between pre and post-neoadjuvant treatment molecular features of melanomas and the tumor immune microenvironment in responders versus non-responders with multiplexed immunohistochemistry (mIHC) and ribonucleic acid-sequencing (RNA-Seq) in patients with stage III melanoma after neoadjuvant vemurafenib/cobimetinib/atezolizumab or cobimetinib/atezolizumab, followed by surgery and adjuvant atezolizumab.

IV. To determine the association between pretreatment tumor PD-L1 and RFS in patients with stage III melanoma receiving neoadjuvant vemurafenib/ cobimetinib/ atezolizumab or cobimetinib/atezolizumab, followed by surgery and adjuvant atezolizumab.

OUTLINE: Participants are assigned to 1 of 2 groups.

ARM A (BRAF mutant): Participants receive vemurafenib orally (PO) twice daily (BID) on days 1-28, cobimetinib PO once daily (QD) on days 1-21, and atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15 of courses 2 and 3. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

ARM B (BRAF wild-type): Participants receive cobimetinib as in Arm A, and atezolizumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Within 2-4 weeks after treatment, participants undergo surgery then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeat every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed every 3 months for up to 3 years.

Study Design

Conditions

Clinical Stage III Cutaneous Melanoma AJCC v8

Intervention

Atezolizumab, Cobimetinib, Vemurafenib

Location

University of Minnesota/Masonic Cancer Center
Minneapolis
Minnesota
United States
55455

Status

Not yet recruiting

Source

Mayo Clinic

Results (where available)

View Results

Links

Published on BioPortfolio: 2018-06-18T02:03:11-0400

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Medical and Biotech [MESH] Definitions

A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.

An unpigmented malignant melanoma. It is an anaplastic melanoma consisting of cells derived from melanoblasts but not forming melanin. (Dorland, 27th ed; Stedman, 25th ed)

Clinically atypical nevi (usually exceeding 5 mm in diameter and having variable pigmentation and ill defined borders) with an increased risk for development of non-familial cutaneous malignant melanoma. Biopsies show melanocytic dysplasia. Nevi are clinically and histologically identical to the precursor lesions for melanoma in the B-K mole syndrome. (Stedman, 25th ed)

A disease caused by any of a number of species of protozoa in the genus LEISHMANIA. There are four major clinical types of this infection: cutaneous (Old and New World) (LEISHMANIASIS, CUTANEOUS), diffuse cutaneous (LEISHMANIASIS, DIFFUSE CUTANEOUS), mucocutaneous (LEISHMANIASIS, MUCOCUTANEOUS), and visceral (LEISHMANIASIS, VISCERAL).

Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.

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