Sorafenib in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery

Stage IV Melanoma Clinical Trial

Official title:

A Phase II Study of BAY 43-9006 (NSC 724772) in Unresectable Stage III and IV Melanoma (IND 69,869)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00119249
• Other study ID #: NCI-2012-02659
• Secondary ID: NYWCCC-NYU-0438N
• Status: Completed
• Phase: Phase 2
• First received: July 12, 2005
• Last updated: January 14, 2013
• Start date: June 2005

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. This phase II trial is studying how well sorafenib works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery

Description:

PRIMARY OBJECTIVES:

I. Determine the efficacy of sorafenib, in terms of anti-tumor effects and proportion of clinical responses, in patients with previously untreated unresectable stage III or stage IV melanoma.

SECONDARY OBJECTIVES:

I. Correlate the efficacy of this drug with the presence of mutant or wild-type BRAF gene in tumors of these patients.

II. Determine the toxicity profile of this drug in these patients. III. Correlate serum cryptic collagen epitopes with the extent of tumor burden, invasion, and metastasis in patients treated with this drug.

IV. Determine the potential of serum cryptic collagen epitopes to serve as a surrogate marker for monitoring the course of disease in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to presence of BRAF gene mutation in tumor sample (yes vs no).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 26-74 patients (13-37 per stratum) will be accrued for this study within 5.2-18.5 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed unresectable melanoma

• Stage III or IV disease

• Measurable disease, defined as = 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan

• Disease amenable to biopsy (first 13 patients in each stratum only)

• Brain metastases allowed provided the following criteria are met:

• Disease has remained radiologically stable for = 6 weeks after completion of whole-brain radiotherapy and remains stable at the time of study entry

• No mass effect present by radiology

• No requirement for steroid therapy to control symptoms of brain metastases

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• At least 3 months

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• No evidence of bleeding diathesis

• AST and ALT = 2.5 times upper limit of normal (ULN)

• Bilirubin = 2 times ULN

• Creatinine = 1.5 times ULN

• No uncontrolled hypertension

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No psychiatric illness that would preclude study compliance

• No pre-existing non-hematological dysfunction = grade 2

• No ongoing or active infection

• No history of serious allergic reaction to eggs

• Able to swallow pills

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or other non-invasive carcinoma

• No other uncontrolled illness

• Not specified

• No prior systemic chemotherapy for metastatic disease

• See Disease Characteristics

• See Disease Characteristics

• No other concurrent investigational agents

• No concurrent therapeutic anticoagulation

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer therapy

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Stage III Melanoma
• Stage IV Melanoma

Intervention

Drug:
• sorafenib tosylate
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (RR) defined as is either a complete or a partial response using RECIST criteria	The overall response rate along with subgroup-specific response rates will be estimated at the end of the trial along with 95% confidence interval.	56 days	No
Secondary	Time to progression	Kaplan-Meier estimates will be calculated for time to progression and overall survival, and medians, along with two-sided 95% confidence intervals, will be reported.	From the first day of treatment until the first documentation of disease progression, assessed up to 3.5 years	No
Secondary	Toxicity assessed using NCI CTCAE version 3.0	All adverse events without regard to causal relationship and by causal relationship to study drugs will be summarized.	Up to 3.5 years	Yes
Secondary	Changes in BRAF, P-MAPK, CDK4, and cyclin D1 levels	The proportion of patients with decreases in levels of BRAF, CDK4, or phospho-MAPK will be estimated along with 95% confidence intervals.	Baseline and up to 3.5 years	No
Secondary	Overall survival	Kaplan-Meier estimates will be calculated for time to progression and overall survival, and medians, along with two-sided 95% confidence intervals, will be reported.	Up to 3.5 years	No