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S0438: Sorafenib With Either Temsirolimus or Tipifarnib in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed By Surgery
The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2009 by Southwest Oncology Group.   Recruitment status was  Active, not recruiting

First Received on January 24, 2006.   Last Updated on July 18, 2011   History of Changes
Sponsor: Southwest Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00281957
  Purpose

RATIONALE: Sorafenib, temsirolimus, and tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor by blocking blood flow to the tumor. It is not yet known whether sorafenib is more effective when given together with temsirolimus or tipifarnib in treating patients with malignant melanoma.

PURPOSE: This randomized phase II trial is studying how well giving sorafenib together with either temsirolimus or tipifarnib works in treating patients with stage IV melanoma that cannot be removed by surgery.


Condition Intervention Phase
Melanoma (Skin)
Drug: sorafenib tosylate
Drug: temsirolimus
Drug: tipifarnib
Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of BAY 43-9006 (SORAFENIB; NSC-724772) With Either CCI-779 (TEMSIROLIMUS; NSC-683864) or R115777 (TIPIFARNIB: NSC-702818) in Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Response rate (confirmed and unconfirmed and complete and partial) [ Designated as safety issue: No ]
  • 4-month progression-free survival [ Designated as safety issue: No ]
  • Safety and tolerability in terms of long-term side effects and toxic effects [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: August 2007
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
Drug: sorafenib tosylate
Given orally
Drug: temsirolimus
Given IV
Experimental: Arm II
Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
Drug: sorafenib tosylate
Given orally
Drug: tipifarnib
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Compare the response rate (confirmed and unconfirmed and complete and partial) in patients with unresectable stage IV malignant melanoma treated with sorafenib in combination with either temsirolimus or tipifarnib.
  • Compare the 4-month progression-free survival rate of patients treated with these regimens.
  • Compare the safety and tolerability of these regimens, with an emphasis on long-term side effects and toxic effects, in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to metastatic (M) stage (M1a/b vs M1c). Patients are randomized to 1 of 2 treatment arms.

  • Arm I (reopened to accrual as of 8/15/2009): Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
  • Arm II (closed to accrual as of 8/15/2009): Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

All patients undergo CT scan or MRI at baseline and in week 9.

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

PROJECTED ACCRUAL: A total of 110 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant melanoma of cutaneous origin

    • Patients with unknown primary allowed
  • Stage IV disease
  • Measurable disease by physical examination, CT scan, MRI or plain x-ray
  • Unresectable disease

    • Residual or recurrent disease after prior surgery for stage IV disease allowed

      • Residual tumor at the site of incomplete resection may be included only as nonmeasurable disease
  • Must have serum lactate dehydrogenase (LDH) levels measured
  • Must have tissue specimens available
  • No history of brain metastases

    • Negative brain CT scan or MRI within the past 42 days

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT or SGPT ≤ 2.5 times ULN (5 times ULN if hepatic metastases)
  • Creatinine ≤ 1.5 times ULN
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Fasting cholesterol ≤ 350 mg/dL (lipid-lowering agents allowed)
  • Triglycerides ≤ 300 mg/dL (lipid-lowering agents allowed)
  • No symptomatic sensory neuropathy ≥ grade 2
  • No evidence of bleeding diathesis or coagulopathy
  • No congestive heart failure
  • No myocardial infarction within the past 2 months
  • No New York Heart Association class III or IV heart disease
  • No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, prior surgical procedure affecting absorption, or active peptic ulcer disease)
  • No known allergy to imidazoles (e.g. clotrimazole, ketoconazole, miconazole, or econazole)
  • No history of allergic reaction to compounds of similar chemical or biologic composition as tipifarnib
  • No hypertension with systolic blood pressure (BP) > 140 mm Hg or diastolic BP > 90 mm Hg

    • Patients with well-controlled hypertension allowed
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled diabetes
  • No uncontrolled chronic renal or liver disease
  • No active uncontrolled infection
  • No other severe or uncontrolled medical disease
  • No psychologic or medical condition that would preclude study treatment or compliance
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, adequately treated stage I or II cancer that is in complete remission, or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 90 days since prior adjuvant therapy, including cytotoxic agents
  • At least 28 days since prior radiotherapy
  • At least 28 days since prior surgery to remove the tumor
  • No prior systemic therapy for stage IV melanoma
  • No prior therapy with agents targeting farnesyl transferase, the MAP kinase pathway, or vascular endothelial growth factors (VEGF) or receptors (VEFGR), including drugs such as sorafenib, temsirolimus, or tipifarnib
  • Concurrent lipid-lowering agents allowed
  • Not requiring full-dose anticoagulation for recent thrombotic event
  • No concurrent highly active antiretroviral therapy (HAART) in HIV-positive patients
  • No concurrent use of any of the following:

    • Dilantin
    • Carbamazepine
    • Phenobarbital
    • Rifampin
    • Hypericum perforatum (St. John's wort)
    • Ketoconazole
    • Itraconazole
    • Ritonavir
    • Cyclosporine
    • Phenytoin
    • Grapefruit juice
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00281957

  Show 252 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Kim A. Margolin, MD Beckman Research Institute
Principal Investigator: Vernon K. Sondak, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier: NCT00281957     History of Changes
Other Study ID Numbers: CDR0000454925, U10CA032102, SWOG-S0438
Study First Received: January 24, 2006
Last Updated: July 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
stage IV melanoma
recurrent melanoma

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
Sirolimus
Everolimus
Tipifarnib
Sorafenib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012