Carboplatin and Paclitaxel With or Without Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Melanoma
This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00110019
First received: May 3, 2005
Last updated: December 20, 2012
Last verified: December 2012
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Purpose
This randomized phase III trial is studying carboplatin, paclitaxel, and sorafenib to see how well they work compared to carboplatin and paclitaxel in treating patients with unresectable stage III or stage IV melanoma. 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 stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and paclitaxel together with sorafenib is more effective than carboplatin and paclitaxel in treating melanoma
| Condition | Intervention | Phase |
|---|---|---|
|
Mucosal Melanoma Recurrent Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma |
Drug: sorafenib tosylate Other: placebo Drug: carboplatin Drug: paclitaxel Other: pharmacological study Other: laboratory biomarker analysis |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | A Double-Blind, Randomized, Placebo-Controlled Phase III Trial of Carboplatin, Paclitaxel and Sorafenib Versus Carboplatin, Paclitaxel and Placebo in Patients With Unresectable Locally Advanced or Stage IV Melanoma |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Overall Survival [ Time Frame: Survival was assesed every 3 months if patient is < 2 years from study entry. Every 6 months is patient is 2-5 years from study entry. ] [ Designated as safety issue: No ]Overall survival is defined as time from study entry to death from any cause. The comparison of overall survival was conducted in intention-to-treat population.
Secondary Outcome Measures:
- Progression-free Survival [ Time Frame: Tumor response was assessed after every 2 cycles during cycle 1 through 10, and every 3 cycles after cycle 10. Survival was assesed every 3 months if patient is < 2 years from study entry, and every 6 months if 2-5 years from study entry. ] [ Designated as safety issue: No ]Progression-free survival was defined as time from study entry to disease progression or death from any cause, whichever occurred first. Patients without disease progression were censored at last date of assessment. Disease progression was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0.
- Objective Response (Complete and Partial Response) Rate [ Time Frame: Tumor response was assessed after every 2 cycles during cycle 1 through 10. After cycle 10, tumor response was assessed after every 3 cycles. ] [ Designated as safety issue: No ]Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Objective response =complete response (CR) + partial response (PR). Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of longest diameters.
| Enrollment: | 823 |
| Study Start Date: | June 2005 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (sorafenib tosylate, paclitaxel, carboplatin)
Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral sorafenib twice daily on days 2-19.
|
Drug: sorafenib tosylate
Given orally
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
|
Placebo Comparator: Arm II (carboplatin, paclitaxel)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 2-19.
|
Other: placebo
Given orally
Other Name: PLCB
Drug: carboplatin
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To compare the overall survival of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib.
II. To compare progression-free survival, response rate, and safety of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib.
III. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib including angiogenesis, monooxygenases polymorphisms and MDR.
IV. To assess the association of expression markers in the patient tumor with clinical outcome.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive paclitaxel intravenously (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
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have a history of cutaneous, mucosal or unknown primary site
Patients who have received prior systemic cytotoxic chemotherapy for treatment of melanoma are ineligible; the following groups are eligible with regard to prior systemic therapy either in the adjuvant or metastatic disease setting:
- No prior therapy
- Immunotherapy consisting of Interferon, Interleukin-2, GM-CSF or vaccine
- One prior investigational therapy (cannot be chemotherapy or an inhibitor of Ras, Raf, or MEK) NOTE: Chemotherapy given via isolated limb perfusion is allowed
- Prior radiation therapy is allowed; however, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions
- All sites of disease must be evaluated within 4 weeks of registration; patients must have measurable disease as defined by RECIST
- ECOG performance status of 0 or 1
- White blood count >= 3,000/mm^3
- Absolute granulocyte count >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Serum creatinine =< 2.0 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40ml/min (neither drug is cleared by the kidney)
- Total Bilirubin =< 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease)
- INR =< 1.5 and a PTT within normal limits (patients who are on therapeutic anticoagulation with warfarin should have documentation of a normal PT/PTT prior to initiating that therapy)
- Patients must not have ocular melanoma
- Patients must have discontinued immunotherapy or radiation therapy at least 4 weeks prior to initiation of treatment and recovered from adverse events due to those agents
- Patients must not receive any other investigational agents during the period on study or the four weeks prior to initiation of treatment
- Patients must not have a history or clinical evidence of brain metastasis; patients must be evaluated with a head MRI within 4 weeks prior to enrollment
- Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease free for >= 5 years prior to the time of randomization
- Patients must not have any evidence of bleeding diathesis
- Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's Wort
- Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk
- All females of childbearing potential must have a blood test or urine study within 4 weeks prior to registration to rule out pregnancy
- The effects of sorafenib, carboplatin and paclitaxel on the developing human fetus are unknown; for this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well
- HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with sorafenib, carboplatin or paclitaxel is unknown; appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00110019
Locations
| United States, Massachusetts | |
| Eastern Cooperative Oncology Group | |
| Boston, Massachusetts, United States, 02215 | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Keith Flaherty | Eastern Cooperative 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: | NCT00110019 History of Changes |
| Other Study ID Numbers: | NCI-2012-02978, E2603, U10CA021115, CDR0000423315 |
| Study First Received: | May 3, 2005 |
| Results First Received: | August 28, 2012 |
| Last Updated: | December 20, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas 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 May 19, 2013