Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Carboplatin and Paclitaxel With or Without Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	ECOG-E2603 E2603, NCT00110019

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. Compare the overall survival of patients with unresectable stage III or stage IV melanoma treated with carboplatin and paclitaxel with vs without sorafenib.

Secondary

1. Compare progression-free survival and response rate in patients treated with these regimens.
2. Compare the safety of these regimens in these patients.

Tertiary

1. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib including angiogenesis, monooxygenases polymorphisms and MDR.
2. IV. Assess the association of expression markers in the patient tumor with clinical outcome.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed melanoma meeting 1 of the following stage criteria:
  • Unresectable stage III disease
  • Stage IV disease



• Must have 1 of the following melanoma types:
  • Cutaneous
  • Mucosal
  • Unknown primary site



• Measurable disease
  • Prior radiotherapy to a measurable lesion allowed provided there is radiographic evidence of disease progression of that lesion



• No ocular melanoma



• No history or clinical evidence of brain metastasis by brain MRI

Prior/Concurrent Therapy:

Biologic therapy

• Prior interferon, interleukin-2, sargramostim (GM-CSF), or vaccine allowed in the adjuvant or metastatic setting
• At least 4 weeks since prior immunotherapy and recovered

Chemotherapy

• No prior systemic cytotoxic chemotherapy for the treatment of melanoma in the adjuvant or metastatic setting
  • Chemotherapy given via isolated limb perfusion is allowed

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• No more than 1 prior investigational therapy in the adjuvant or metastatic setting
  • No prior investigational therapy comprising inhibitors of Ras, Raf, or MEK
• At least 4 weeks since prior and no other concurrent investigational agents
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• No evidence of bleeding diathesis

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (< 3.0 times ULN if Gilbert's disease is present)
• AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if liver metastases are present)
• INR ≤ 1.5
• PTT normal

Renal

• Creatinine ≤ 2.0 times ULN

  OR

• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• No uncontrolled hypertension
• No myocardial infarction
• No unstable angina
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No peripheral vascular disease > grade 2 within the past year
• No other clinically significant cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HIV positivity
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of breast
• No ongoing or active infection requiring parenteral antibiotics
• No other serious illness
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

A total of 800 patients will be accrued for this study within 40 months.

Outcomes

Overall survival

Progression-free survival as assessed by RECIST criteria
Objective response (complete and partial response) rate

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior therapy in the adjuvant or metastatic setting (no prior therapy vs prior therapy with interferon, interleukin-2, or sargramostim [GM-CSF] vs 1 prior investigational therapy that is not chemotherapy or an inhibitor of Ras, Raf, or MEK), disease stage (unresectable stage III vs M1a or M1b vs M1c), or ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral sorafenib twice daily on days 2-19.



• Arm II: Patients receive paclitaxel and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 2-19.

In both arms, treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or who achieve a partial response or complete response may continue to receive sorafenib or placebo alone twice daily on days 1-21. Courses with sorafenib or placebo repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Keith Flaherty, MD, Protocol chair		Ph: 215-662-7402
Lynn Mara Schuchter, MD, Protocol co-chair		Ph: 215-662-7907 Email: Lynn.Schuchter@uphs.upenn.edu

Southwest Oncology Group

Lawrence Flaherty, MD, Study coordinator		Ph: 313-576-8715; 800-527-6266 Email: flaherty@karmanos.org

Related Information

Featured trial article

Registry Information
Official Title		A Double-blind, Randomized, Placebo-controlled Phase III Trial of Carboplatin, Paclitaxel, and BAY 43-9006 Versus Carboplatin, Paclitaxel, and Placebo in Patients With Unresectable Stage III or IV Melanoma
Trial Start Date		2005-06-23
Trial Completion Date		2010-04-30 (estimated)
Registered in ClinicalTrials.gov		NCT00110019
Date Submitted to PDQ		2005-02-28
Information Last Verified		2008-11-06
NCI Grant/Contract Number		CA21115

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