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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00329641
First received: May 23, 2006
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Ciliary Body and Choroid Melanoma, Medium/Large Size
Extraocular Extension Melanoma
Iris Melanoma
Metastatic Intraocular Melanoma
Recurrent Intraocular Melanoma
Drug: carboplatin
Drug: paclitaxel
Drug: sorafenib tosylate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of BAY 43-9006 (Sorafenib; NSC-724772) in Combination With Carboplatin and Paclitaxel in Patients With Metastatic Uveal Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response Rate (Complete and Partial Response) [ Time Frame: Every 6 weeks for the first 8 cycles of therapy, then every three cycles (9 weeks) until progression ] [ Designated as safety issue: No ]
    Complete response corresponds to complete disappearance of all measurable and non-measurable lesions with no new lesions. Partial response corresponds to greater than or equal to 30fi decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease.


Secondary Outcome Measures:
  • One-year Overall Survival [ Time Frame: Every 6-9 weeks until progression, after progression every six months for first two years and annually thereafter up to 3 for up to 3 years after registration or until death ] [ Designated as safety issue: No ]
    Measured from date of registration to study until death due to any caused with observations last known to be alive censored at the date of last contact

  • 6-month Progression-free Survival [ Time Frame: Every 6 weeks for the first 8 cycles of therapy, and then every 9 weeks until disease progression for up to 3 years after registration or until death ] [ Designated as safety issue: No ]
    Measured from the date of registration to the first of progression or death due to any cause with patients last known to be alive and progression-free censored at the date of last contact

  • Toxicity [ Time Frame: Weekly during the first cycle of therapy, then prior to each cycle (one cycle = 3 weeks) ] [ Designated as safety issue: Yes ]
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event


Enrollment: 40
Study Start Date: February 2011
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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. ]

Drug: carboplatin
Given IV
Drug: paclitaxel
Given IV
Drug: sorafenib tosylate
Given orally

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00329641

Locations
United States, Texas
Southwest Oncology Group
San Antonio, Texas, United States, 78245
Sponsors and Collaborators
Investigators
Principal Investigator: Ana Aparicio Southwest Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00329641     History of Changes
Other Study ID Numbers: NCI-2009-00777, NCI-2009-00777, CDR0000467188, S0512, S0512, S0512, U10CA032102
Study First Received: May 23, 2006
Results First Received: June 5, 2012
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Sorafenib
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014