Radiation Use During Vemurafenib Treatment

Radiation Use During Vemurafenib and Cobimetinib Treatment in Patients With BRAFV600 Mutated Stage IV or Unresectable Stage III Melanoma

Patients are being asked to take part because they have melanoma that has spread to other organs in their body (metastatic). As part of this study, patients will receive radiation therapy and an approved drug (Vemurafenib).

Study Overview

• Status: Withdrawn
• Conditions: Stage IV Melanoma; BRAFV600 Mutation
• Intervention / Treatment: Radiation: Radiation therapy; Drug: Vemurafenib

Detailed Description

Patients will be treated with vemurafenib plus radiation therapy (RT) based upon the administration schedule. The starting dose of vemurafenib will be the patient's baseline tolerating dose, between 720 - and 960 mg by mouth. Patients must be tolerating at a minimum 720mg for one cycle (28 days) prior to enrollment.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years old
• Diagnosis of BRAFV600 mutated Stage IV or unresectable Stage III melanoma
• Actively receiving treatment with vemurafenib as single agent and tolerating at least 720 mg bid for one cycle (28 days).

• In the opinion of the investigator, patients who are progressing in an area where radiation may provide benefit from either:

  • Symptom control
  • Oligo-progression, defined as progression in up to 3 areas where focal treatment would provide benefit.

• Patients with brain metastases will be allowed provided they meet all of the following criteria:

  • Small, < 1cm metastases which are untreated are allowed so long as in the opinion of the investigator they do not require immediate treatment by radiation or surgery
  • Asymptomatic, treated brain metastases which are stable for 4 weeks prior to study entry are allowed
  • If patients are requiring steroids for their brain metastases, they must be on a stable dose for two weeks prior to study entry, and maintain that steroid dosing during the radiation treatments
• Adequate bone marrow function as defined by: ANC > 1.0 k/uL, Platelets > 75 k/uL, Hemoglobin > 8 g/dL
• Adequate hepatic function: Total bilirubin < 1.5 times the institutional upper limit of normal, ALT/AST < 2.5 times the institutional upper limit of normal
• Adequate renal function as defined by serum creatinin < 1.5 times the upper limit of normal.
• Negative serum pregnancy test at screening for women of child bearing potential within 10 days of starting vemurafenib treatment . Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year
• Fertile men and women must agree to use an acceptable method of birth control during treatment and for at least 2 months after discontinuation of vemurafenib.
• Able and willing to provide informed consent to an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

• Screening QTc interval > 450 msec on EKG
• Known HIV positivity or AIDS-related illness, or active HBV, or active HCV.
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension, cerebrovascular accident or transient ischemic attack, or symptomatic pulmonary embolism.
• Malabsorption disorder that would preclude adequate vemurafenib absorption.
• Other medical condition present that in the opinion of the investigator will hinder the subjects ability to complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All participants	Radiation: Radiation therapy; Per standard of care; Drug: Vemurafenib; The starting dose of vemurafenib will be the patient's baseline tolerating dose, between 720 - and 960 mg PO bid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events as a measure of safety and tolerability	To evaluate the safety of radiation combined with vemurafenib treatment in patients with BRAFV600 mutated Stage IV or unresectable Stage III melanoma	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	To evaluate response rates as assessed by RECIST criteria 1.1, at baseline, and at 8 week intervals throughout the study	36 months

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Kenneth Grossmann, MD, PhD, Huntsman Cancer Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2017
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: April 26, 2013
• First Posted (Estimate): May 1, 2013

Study Record Updates

• Last Update Posted (Actual): May 24, 2017
• Last Update Submitted That Met QC Criteria: May 22, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: HCI64498

Drug and device information, study documents

• 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