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

Primary Purpose

Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
carboplatin
paclitaxel
sorafenib tosylate
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ciliary Body and Choroid Melanoma, Medium/Large Size

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Southwest Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (carboplatin, paclitaxel, sorafenib)

Arm Description

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. ]

Outcomes

Primary Outcome Measures

Response Rate (Complete and Partial Response)
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
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
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
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Full Information

First Posted
May 23, 2006
Last Updated
July 25, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00329641
Brief Title
Sorafenib, Carboplatin, and Paclitaxel in Treating Patients With Stage IV Melanoma of the Eye
Official Title
Phase II Trial of BAY 43-9006 (Sorafenib; NSC-724772) in Combination With Carboplatin and Paclitaxel in Patients With Metastatic Uveal Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Metastatic Intraocular Melanoma, Recurrent Intraocular Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (carboplatin, paclitaxel, sorafenib)
Arm Type
Experimental
Arm Description
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. ]
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
sorafenib tosylate
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Response Rate (Complete and Partial Response)
Description
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.
Time Frame
Every 6 weeks for the first 8 cycles of therapy, then every three cycles (9 weeks) until progression
Secondary Outcome Measure Information:
Title
One-year Overall Survival
Description
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
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
Title
6-month Progression-free Survival
Description
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
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
Title
Toxicity
Description
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
Time Frame
Weekly during the first cycle of therapy, then prior to each cycle (one cycle = 3 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ana Aparicio
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Oncology Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78245
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23226204
Citation
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.
Results Reference
derived

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

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