Sorafenib, Carboplatin, and Paclitaxel in Treating Patients With Stage IV Melanoma of the Eye

NCT ID: NCT00329641

Last Updated: 2014-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2012-11-30

Brief Summary

This phase II trial is studying how well sorafenib works when given together with carboplatin and paclitaxel in treating patients with stage IV melanoma of the eye. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may help carboplatin and paclitaxel work better by making tumor cells more sensitive to the drugs. Sorafenib may also stop the growth of melanoma by blocking some of the enzymes needed for tumor cell growth and by blocking blood flow to the tumor. Giving sorafenib together with carboplatin and paclitaxel may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the response rate (confirmed and unconfirmed, complete and partial response) of patients with stage IV uveal melanoma treated with sorafenib, carboplatin, and paclitaxel.

SECONDARY OBJECTIVES:

I. Determine the overall and progression-free survival of patients treated with this regimen.

II. Determine the toxic effects of this regimen in these patients. III. Determine, preliminarily, the relationship between clinical outcomes and baseline microvessel density (MVD) in tumor specimens, changes in vascular endothelial growth factor (VEGF) levels in plasma and urine, changes in MVD, changes in VEGF receptor-2 phosphorylation in tumor, and/or changes in ERK 1/2 phosphorylation in stimulated lymphocytes and tumor.

OUTLINE: This is a non-randomized, open-label, multicenter study.

Patients receive carboplatin IV and paclitaxel IV once on day 1 and oral sorafenib twice daily on days 2-19. Treatment repeats every 21 days for up to 6 courses.* After 6 courses, patients continue to receive oral sorafenib alone twice daily in the absence of disease progression or unacceptable toxicity.

[Note: *If sorafenib is discontinued prior to course 6, patients may continue to receive carboplatin and paclitaxel for up to 6 courses; if carboplatin and paclitaxel are discontinued prior to course 6, patients may continue to receive sorafenib alone twice daily on days 1-21 of each course in the absence of disease progression or unacceptable toxicity. ]

After completion of study treatment, patients are followed periodically for up to 3 years.

Conditions

Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma

Study Design

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

Study Groups

Treatment (carboplatin, paclitaxel, sorafenib)

Patients receive carboplatin IV and paclitaxel IV once on day 1 and oral sorafenib twice daily on days 2-19. Treatment repeats every 21 days for up to 6 courses.* After 6 courses, patients continue to receive oral sorafenib alone twice daily in the absence of disease progression or unacceptable toxicity.

[Note: *If sorafenib is discontinued prior to course 6, patients may continue to receive carboplatin and paclitaxel for up to 6 courses; if carboplatin and paclitaxel are discontinued prior to course 6, patients may continue to receive sorafenib alone twice daily on days 1-21 of each course in the absence of disease progression or unacceptable toxicity. ]

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

sorafenib tosylate

Intervention Type: DRUG

Given orally

Interventions

carboplatin

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

sorafenib tosylate

Given orally

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Criteria:

• Histologically proven uveal melanoma
• Must have documented disease progression during or after =< 1 prior systemic treatment
• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan
• No tumor involving major vessels
• Zubrod performance status 0-1
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Creatinine =< 2 times upper limit of normal (ULN)
• Bilirubin =< 2 times ULN
• SGOT or SGPT =< 2 times ULN (5 times ULN if hepatic metastasis present)
• INR in range (usually between 2 and 3)
• No active bleeding
• No bleeding diathesis, active coagulopathy, or pathological condition that carries a high risk of bleeding
• No condition (e.g., gastrointestinal tract disease) affecting ability to take oral medication or requiring IV alimentation
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for 5 years
• At least 28 days since prior systemic treatment for this disease comprising 1 of the following: single chemotherapy agent/regimen; single immunotherapy agent/regimen; single investigational treatment agent/regimen
• At least 21 days since prior major surgery
• No prior sorafenib or any other agents targeting raf kinase or vascular endothelial growth factor (VEGF) or VEGF receptor
• No prior surgical procedures affecting absorption
• No concurrent systemic corticosteroid therapy
• Topical and/or inhaled steroids are allowed
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
• No prophylactic granulocyte/platelet colony-stimulating factors during the first course of treatment
• Concurrent full-dose oral anticoagulants (e.g., warfarin) are allowed provided all of the following criteria are met: in-range INR ; stable dose of oral anticoagulant; no active bleeding or high risk of bleeding
• Stage IV disease
• No known varices
• No uncontrolled hypertension with systolic blood pressure (BP) > 140 mm Hg or diastolic BP > 90 mm Hg
• No significant traumatic injury within the past 21 days
• No active, uncontrolled peptic ulcer disease

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ana Aparicio

Role: PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Locations

Southwest Oncology Group

San Antonio, Texas, United States

Countries

United States

References

Bhatia S, Moon J, Margolin KA, Weber JS, Lao CD, Othus M, Aparicio AM, Ribas A, Sondak VK. Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. PLoS One. 2012;7(11):e48787. doi: 10.1371/journal.pone.0048787. Epub 2012 Nov 30.

Reference Type: DERIVED

PMID: 23226204 (View on PubMed)

Other Identifiers

NCI-2009-00777

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000467188

Identifier Type: -

Identifier Source: secondary_id

S0512

Identifier Type: -

Identifier Source: secondary_id

S0512

Identifier Type: OTHER

Identifier Source: secondary_id

S0512

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00777

Identifier Type: -

Identifier Source: org_study_id