Clinical trial NCT00098553: Everolimus in Treating Patients With Stage IV Melanoma
Official title: Phase II Trial Of RAD-001 In Metastatic Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-12-08
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as everolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may also stop the growth of melanoma by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with stage IV melanoma.

Detailed description: OBJECTIVES:

Primary

* Determine the median time to disease progression in patients with stage IV malignant melanoma treated with everolimus.

Secondary

* Determine the median overall survival of patients treated with this drug.
* Determine the clinical benefit rates (i.e., stable disease, partial remission, and complete response rates) in patients treated with this drug.
* Determine the toxicity profile of this drug in these patients.
* Determine changes in serum vascular endothelial growth factor levels in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months until disease progression and then every 4 months for up to 5 years after registration.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant melanoma for which no known standard or potentially curative therapy exists or has been proven to extend life expectancy

  * Stage IV disease
* Measurable disease

  * At least 1 lesion ≥ 20 mm by CT scan or MRI OR ≥ 10 mm by spiral CT scan
* No intracranial disease

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9.0 g/dL
* No bleeding diathesis

Hepatic

* AST ≤ 3 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 3 ULN
* INR ≤ 1.5

Renal

* Creatinine ≤ 1.5 times ULN

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Willing to refrain from foods high in fat content
* No uncontrolled infection
* No immunosuppression from any cause (e.g., known HIV infection)
* No other malignancy within the past 5 years except basal cell or squamous cell skin cancer treated with local resection only
* No other severe condition that would preclude study participation or compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 4 weeks since prior immunotherapy or biologic therapy

Chemotherapy

* More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
* No prior sirolimus or its analogues for any indication
* No other concurrent chemotherapy

Endocrine therapy

* No concurrent steroids

Radiotherapy

* More than 4 weeks since prior radiotherapy to head and neck area
* More than 4 weeks since prior radiosurgery
* No prior radiotherapy to \> 30% of bone marrow
* No concurrent radiotherapy

Surgery

* Not specified

Other

* At least 1 week since prior and no concurrent CYP3A4 inducers
* No concurrent warfarin
* No concurrent cytotoxic agents
* No other concurrent experimental drugs
* No other concurrent immunosuppressive therapy

Primary outcomes:
measure: Proportion of patients with progression-free disease at 16 weeks
timeFrame: at 16 weeks
Secondary outcomes:
measure: Median overall survival
timeFrame: Up to 5 years
measure: Tumor response rate for 2 consecutive evaluations at least 8 weeks apart
timeFrame: Up to 5 years
measure: Toxicity as measured by CTCAE v. 3.0
timeFrame: Up to 5 years
measure: disease progression
timeFrame: at 16 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center - East
state: Illinois
city: Moline
country: United States
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Ottumwa
country: United States
facility: McCreery Cancer Center at Ottumwa Regional
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: West Des Moines
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology, Limited - Iron Mountain
state: Michigan
city: Alexandria
country: United States
state: Minnesota
city: Bemidji
country: United States
facility: MeritCare Clinic - Bemidji
state: Minnesota
city: Brainerd
country: United States
facility: Brainerd Medical Center
state: Minnesota
city: Brainerd
country: United States
facility: St. Joseph's Medical Center
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fergus Falls
country: United States
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Lichfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Montevideo
country: United States
facility: Chippewa County - Montevideo Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Sartell
country: United States
facility: Adult and Pediatric Urology, P.L.L.P.
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Cancer Center
state: Minnesota
city: St Paul
country: United States
facility: St. Joseph's Hospital
state: Minnesota
city: St. Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Health Services
state: Minnesota
city: St. Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Woodwinds Health Campus
state: Minnesota
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center Cancer Center
state: North Dakota
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Broadway
state: North Dakota
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Franciscan Skemp Healthcare - La Crosse Campus
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Ravi D. Rao, MD, MBBS
role: STUDY_CHAIR
affiliation: Coborn Cancer Center
name: Harold E. Windschitl, MD
affiliation: Mayo Clinic
name: William J. Maples, MD
affiliation: Mayo Clinic
name: Michael K. Gornet, MD
affiliation: Mayo Clinic
name: James N. Ingle, MD
affiliation: Mayo Clinic
name: Edward T. Creagan, MD
affiliation: Mayo Clinic
name: Judith S. Kaur, MD
affiliation: Mayo Clinic Hospital
name: Barbara A. Pockaj, MD
affiliation: Mayo Clinic
name: Evanthia Galanis, MD
affiliation: Mayo Clinic
name: Charles L. Loprinzi, MD
affiliation: Mayo Clinic
name: Henry C. Pitot, MD
affiliation: Mayo Clinic
name: Lori A. Erickson, MD
affiliation: Mayo Clinic
name: Val J. Lowe, MD
References:
citation: Rao RD, Allred JB, Windschitl HE, et al.: N0377: results of NCCTG phase II trial of the mTOR inhibitor RAD-001 in metastatic melanoma. [Abstract] J Clin Oncol 25 (Suppl 18): A-8530, 479s, 2007.
citation: Rao RD, Windschitl HE, Allred JB, et al.: Phase II trial of the mTOR inhibitor everolimus (RAD-001) in metastatic melanoma. [Abstract] J Clin Oncol 24 (Suppl 18): A-8043, 463s, 2006.
citation: Vera Aguilera J, Rao RD, Allred JB, Suman VJ, Windschitl HE, Kaur JS, Maples WJ, Lowe VJ, Creagan ET, Erickson LA, Markovic S. Phase II Study of Everolimus in Metastatic Malignant Melanoma (NCCTG-N0377, Alliance). Oncologist. 2018 Aug;23(8):887-e94. doi: 10.1634/theoncologist.2018-0100. Epub 2018 Apr 17.