Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery

Melanoma (Skin) Clinical Trial

Official title:

A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00521001
• Other study ID #: NCCTG-N0675
• Secondary ID: NCI-2012-02713CD
• Status: Completed
• Phase: Phase 2
• First received: August 24, 2007
• Last updated: August 12, 2016
• Start date: January 2008
• Est. completion date: December 2010

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Giving everolimus together with temozolomide may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving everolimus together with temozolomide works in treating patients with stage IV melanoma that cannot be removed by surgery

Description:

OBJECTIVES:

Primary

• Estimate the 9-week progression-free survival rate for patients with stage IV malignant melanoma treated with everolimus and temozolomide.

Secondary

• Evaluate overall survival time.

• Evaluate time to disease progression.

• Assess the toxicity profile of the combination of everolimus and temozolomide in patients with stage IV malignant melanoma.

• Assess the clinical benefit rate (i.e., stable disease, partial remission, and complete response rates).

• Describe the impact of therapy on parameters of angiogenesis and immunity (systemic and tumor microenvironment).

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and oral temozolomide once a day on days 8-12 for course 1 only. For course 2 and all subsequent courses, patients receive oral everolimus once a day on days 1-5, 8-12, 15-19, and 22-26 and oral temozolomide once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

All patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for relative numbers of T, B, and NK cells via flow cytometry, quantitative immunoglobulin levels (IgG, IgM, and IgA), Tetramer/ELISPOT CTL frequencies to CMV/EBV immunodominant antigens, V beta T cell spectratyping, and VEGF levels via ELISA.

After completion of study treatment, patients are followed every 8 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma with manifestations of metastatic disease.

• Unresectable stage IV malignant melanoma with measurable disease

• Measurable disease defined as at least one lesion with the longest diameter measured as = 20 mm by CT scan or MRI scan OR = 10 mm by spiral CT

• No previously untreated or unstable active brain metastases within the past 3 months

• No known standard therapy for this disease that is potentially curative or proven capable of extending life expectancy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy = 12 weeks

• ANC = 1,500/µL

• Platelet count = 100,000/µL

• Hemoglobin = 9.0 g/dL

• Alkaline phosphatase = 3 times institutional upper limit of normal (ULN)

• Creatinine = 1.5 times ULN

• AST = 3 times ULN

• INR = 1.5

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients and their partners must use effective contraception during and for = 8 weeks after completion of study treatment

• Able to return to a NCCTG institution for follow-up

• Able to forego foods high in fat content 2 hours prior to and 2 hours after administration of everolimus therapy

• Able to provide blood samples for research purposes

• No hypersensitivity to temozolomide, dacarbazine, or any analog of sirolimus

• No history of malignancy within the past 5 years except for basal cell or squamous cell carcinoma of the skin treated with local resection only

• No immunosuppression from any cause, including known HIV infection or chronic immunosuppressive therapy

• No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)

• No serious medical condition that may make it unsafe for a patient to enroll in study, including any of the following:

• Severely impaired lung function (FEV1 < 1 liter), unstable angina pectoris (ongoing symptoms), ongoing symptomatic congestive heart failure (i.e., NYHA class I-IV) refractory to appropriate therapy, or myocardial infarction within the past 6 months, or serious uncontrolled cardiac arrhythmia

• Uncontrolled diabetes in spite of optimal therapy (i.e., a history of fasting serum glucose > 150 mg/dL)

• Any active (acute or chronic) or uncontrolled infection/disorders

• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the study treatment

• Liver disease (i.e., uncompensated cirrhosis or active hepatitis with elevated liver enzymes)

• No bleeding diathesis

• No concurrent severe condition that would make it undesirable for the patient to participate in this trial or that would jeopardize compliance with the trial

PRIOR CONCURRENT THERAPY:

• Must have recovered from effects of prior antineoplastic therapy

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)

• At least 4 weeks since prior immunotherapy

• At least 4 weeks since prior biologic therapy

• At least 4 weeks since prior radiosurgery

• At least 4 weeks since prior investigational therapy for melanoma

• No prior small bowel resection that may significantly alter the absorption of everolimus

• No prior sirolimus or its analogues

• No prior radiotherapy to > 30% of bone marrow

• No concurrent drugs that may induce CYP3A4 activity

• No concurrent warfarin

• No concurrent grapefruit or grapefruit juice

• No concurrent use or planned use of vaccines containing live virus

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Drug:
• everolimus

• temozolomide

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Mason District Hospital	Havana	Illinois
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Southwest Medical Center	Liberal	Kansas
United States	Meeker County Memorial Hospital	Lichfield	Minnesota
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	McDonough District Hospital	Macomb	Illinois
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Hackley Hospital	Muskegon	Michigan
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Mercy Medical Center	Springfield	Ohio
United States	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	North Suburban Medical Center	Thornton	Colorado
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Dronca RS, Allred JB, Perez DG, Nevala WK, Lieser EA, Thompson M, Maples WJ, Creagan ET, Pockaj BA, Kaur JS, Moore TD, Marchello BT, Markovic SN. Phase II study of temozolomide (TMZ) and everolimus (RAD001) therapy for metastatic melanoma: a North Central — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	9-week progression-free survival rate		at 9 weeks	No
Secondary	Survival time		Up to 5 years	No
Secondary	Time to disease progression		Up to 5 years	No
Secondary	Confirmed response rate (complete response and partial response)		Up to 5 years	No