Clinical trial NCT00281957: Sorafenib With Either Temsirolimus or Tipifarnib in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed By Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Melanoma
Stage IV Melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-01-25
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVES:

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.

Eligibility criteria: Criteria:

* 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

Primary outcomes:
measure: Response Rate (Complete and Partial)
timeFrame: Every 8 weeks until progression
measure: 4-month Progression-free Survival
timeFrame: 4 months after registration
Secondary outcomes:
measure: One-year Overall Survival
timeFrame: One year after registration
measure: Toxicity
timeFrame: Weekly during first cycle, every two weeks during the second cycle, and once a cycle further cycles (one cycle = 4 weeks).
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants-Castro Valley
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology Consultants-Fremont
state: California
city: Los Angeles
country: United States
facility: University of Southern California/Norris Cancer Center
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute CCOP
state: California
city: Oakland
country: United States
facility: Larry G Strieff MD Medical Corporation
state: California
city: Oakland
country: United States
facility: Tom K Lee Inc
state: California
city: Pleasanton
country: United States
facility: Valley Care Health System - Pleasanton
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter General Hospital
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center- JC Robinson Regional Cancer Center
state: California
city: Aurora
country: United States
facility: The Medical Center of Aurora
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Exempla Saint Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: Colorado Cancer Research Program CCOP
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: Saint Mary's Hospital and Regional Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Lakewood
country: United States
facility: Saint Anthony Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Leesburg
country: United States
facility: Cancer Centers of Central Florida PA
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Valdosta
country: United States
facility: South Georgia Medical Center
state: Georgia
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Moline
country: United States
facility: Garneau, Stewart C MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Porubcin, Michael MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Sharis, Christine M MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Stoffel, Thomas J MD (UIA Investigator)
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic-Urbana Main
state: Illinois
city: Michigan City
country: United States
facility: Franciscan Saint Anthony Health-Michigan City
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC-William R Bliss Cancer Center
state: Iowa
city: Bettendorf
country: United States
facility: Constantinou, Costas L MD (UIA Investigator)
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Davenport
country: United States
facility: Genesis Medical Center - East Campus
state: Iowa
city: Davenport
country: United States
facility: Genesis Medical Center - West Campus
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Laurel
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Anthony
country: United States
facility: Hospital District Sixth of Harper County
state: Kansas
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Hays
country: United States
facility: Hays Medical Center
state: Kansas
city: Hutchinson
country: United States
facility: Promise Regional Medical Center-Hutchinson
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas-Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Olathe
country: United States
facility: Olathe Cancer Center
state: Kansas
city: Overland Park
country: United States
facility: Radiation Oncology Practice Corporation Southwest
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Topeka
country: United States
facility: Stormont-Vail Regional Health Center
state: Kansas
city: Topeka
country: United States
facility: Saint Francis Hospital and Medical Center - Topeka
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Main Office
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Monroe
country: United States
facility: Louisiana State University Sciences Center- Monroe
state: Louisiana
city: Shreveport
country: United States
facility: Highland Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center Shreveport
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Big Rapids
country: United States
facility: Spectrum Health Big Rapids Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Partners-Hackley Campus
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Mercy Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Litchfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Cape Girardeau
country: United States
facility: Southeast Missouri Hospital
state: Missouri
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation South
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation - North
state: Missouri
city: Billings
country: United States
facility: Montana Cancer Consortium CCOP
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies PC
state: Montana
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Great Falls
country: United States
facility: Berdeaux, Donald MD (UIA Investigator)
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: Saint Peter's Community Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists
state: Montana
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Kearney
country: United States
facility: Good Samaritan Hospital
state: Nebraska
city: Lincoln
country: United States
facility: Nebraska Cancer Research Center
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Cooperstown
country: United States
facility: Mary Imogene Bassett Hospital
state: New York
city: Middletown
country: United States
facility: Orange Regional Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital-Memorial Campus
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Mansfield
country: United States
facility: Mansfield General Hospital-MedCentral Health System
state: Ohio
city: Portland
country: United States
facility: Adventist Medical Center
state: Oregon
city: Portland
country: United States
facility: SWOG
state: Oregon
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Hospital
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: Upstate Carolina CCOP
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Norton
country: United States
facility: Southwest VA Regional Cancer Center
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth Saint Joseph Medical Center
state: Washington
city: Bremerton
country: United States
facility: Harrison HealthPartners Hematology and Oncology-Bremerton
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology PLLC
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical PLLC
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
city: Seattle
country: United States
facility: Group Health Cooperative-Seattle
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Seattle
country: United States
facility: The Polyclinic
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Sedro-Woolley
country: United States
facility: United General Hospital
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Madison
country: United States
facility: Dean Hematology and Oncology Clinic
state: Wisconsin
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
Study officials:
affiliation: SWOG Cancer Research Network
name: Kim Margolin
role: PRINCIPAL_INVESTIGATOR
References: