Sorafenib With Either Temsirolimus or Tipifarnib in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00281957
Recruitment Status : Completed
First Posted : January 25, 2006
Results First Posted : July 10, 2012
Last Update Posted : May 20, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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. 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.

Condition or disease Intervention/treatment Phase
Recurrent Melanoma Stage IV Melanoma Drug: sorafenib tosylate Drug: tipifarnib Drug: temsirolimus Phase 2

Detailed Description:


I. 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.

II. Compare the 4-month progression-free survival rate of patients treated with these regimens.

III. 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.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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
Study Start Date : August 2007
Actual Primary Completion Date : December 2010
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: Arm I (sorafenib, temsirolimus)
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
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

Experimental: Arm II (sorafenib, tipifarnib)
Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

Primary Outcome Measures :
  1. Response Rate (Complete and Partial) [ Time Frame: Every 8 weeks until progression ]
    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.

  2. 4-month Progression-free Survival [ Time Frame: 4 months after registration ]
    Progression was defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed, unequivocal progression of non-measurable disease, appearance of any new lesions, death due to disease without prior documentation of progression and without symptomatic deterioration.

Secondary Outcome Measures :
  1. One-year Overall Survival [ Time Frame: One year after registration ]
  2. Toxicity [ Time Frame: Weekly during first cycle, every two weeks during the second cycle, and once a cycle further cycles (one cycle = 4 weeks). ]
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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
  • Negative brain CT scan or MRI within the past 42 days
  • 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 diabetes
  • 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
  • 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
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • SGOT or SGPT =< 2.5 times ULN (5 times ULN if hepatic metastases)
  • No history of brain metastases
  • Zubrod performance status 0-1

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00281957

  Show 173 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Kim Margolin Southwest Oncology Group

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00281957     History of Changes
Other Study ID Numbers: NCI-2009-00774
NCI-2009-00774 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S0438 ( Other Identifier: SWOG )
S0438 ( Other Identifier: CTEP )
U10CA032102 ( U.S. NIH Grant/Contract )
First Posted: January 25, 2006    Key Record Dates
Results First Posted: July 10, 2012
Last Update Posted: May 20, 2014
Last Verified: April 2013

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents