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

Stage IV Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00281957
• Other study ID #: NCI-2009-00774
• Secondary ID: NCI-2009-00774S0
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2006
• Last updated: May 2, 2014
• Start date: August 2007
• Est. completion date: January 2011

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: January 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Recurrent Melanoma
• Stage IV Melanoma

Intervention

Drug:
• sorafenib tosylate
Given orally
• tipifarnib
Given orally
• temsirolimus
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate (Complete and Partial)	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 30? decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease.	Every 8 weeks until progression	No
Primary	4-month Progression-free Survival	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.	4 months after registration	No
Secondary	One-year Overall Survival		One year after registration	No
Secondary	Toxicity	Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event	Weekly during first cycle, every two weeks during the second cycle, and once a cycle further cycles (one cycle = 4 weeks).	Yes