Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery
Status: | Completed |
---|---|
Conditions: | Skin Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 4/21/2016 |
Start Date: | January 2008 |
End Date: | December 2010 |
A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma
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
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
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.
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.
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
We found this trial at
198
sites
Elkhart General Hospital For over 100 years, the highly skilled professionals of Elkhart General Hospital...
Click here to add this to my saved trials
1200 S Cedar Crest Blvd
Allentown, Pennsylvania 18103
Allentown, Pennsylvania 18103
(610) 402-8000
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest Lehigh Valley Hospital provides a...
Click here to add this to my saved trials
3535 Olentangy River Road
Columbus, Ohio 43214
Columbus, Ohio 43214
(614) 566-5000
Riverside Methodist Hospital Cancer Care Serving central Ohio since 1892, Riverside Methodist is consistently ranked...
Click here to add this to my saved trials
1719 East 19th Avenue
Denver, Colorado 80218
Denver, Colorado 80218
(303) 839-6000
Presbyterian - St. Luke's Medical Center Presbyterian/St. Luke's Medical Center and the Rocky Mountain Hospital...
Click here to add this to my saved trials
1920 Libal Street
Green Bay, Wisconsin 54307
Green Bay, Wisconsin 54307
(920) 433-8889
St. Vincent Hospital Regional Cancer Center Our group of 19 oncologists, including the region's only...
Click here to add this to my saved trials
Avera Cancer Institute Avera, the health ministry of the Benedictine and Presentation Sisters, is a...
Click here to add this to my saved trials
825 N Emporia Ave
Wichita, Kansas 67214
Wichita, Kansas 67214
(316) 261-3200
Via Christi Cancer Center at Via Christi Regional Medical Center Via Christi Health's rich history...
Click here to add this to my saved trials
Click here to add this to my saved trials
McFarland Clinic, PC It has been over 65 years since the founders of McFarland Clinic...
Click here to add this to my saved trials
Click here to add this to my saved trials
Aurora Presbyterian Hospital At The Medical Center of Aurora and Centennial Medical Plaza, we treat...
Click here to add this to my saved trials
Click here to add this to my saved trials
300 North Ave
Battle Creek, Michigan 49017
Battle Creek, Michigan 49017
(269) 245-8000
Battle Creek Health System Cancer Care Center As a proud member of the Battle Creek...
Click here to add this to my saved trials
8111 South Emerson Avenue
Beech Grove, Indiana 46237
Beech Grove, Indiana 46237
(317) 528-5000
St. Francis Hospital and Health Centers - Beech Grove Campus A trusted leader in providing...
Click here to add this to my saved trials
Mary Rutan Hospital The hospital was endowed by the sale of a farm in Ridgeway...
Click here to add this to my saved trials
MeritCare Bemidji Sanford Health is an integrated health system headquartered in the Dakotas and is...
Click here to add this to my saved trials
Mecosta County Medical Center Spectrum Health is a not-for-profit system of care dedicated to improving...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
2900 12th Ave N Ste 160W
Billings, Montana 59101
Billings, Montana 59101
(406) 238-6290
Hematology-Oncology Centers of the Northern Rockies - Billings The physicians and staff of Hematology-Oncology Centers...
Click here to add this to my saved trials
1101 N 27th St # 201
Billings, Montana 59101
Billings, Montana 59101
(406) 237-3585
St. Vincent Healthcare Cancer Care Services The Sisters of Charity of Leavenworth, Kansas, founded St....
Click here to add this to my saved trials
Bismarck Cancer Center The Bismarck Cancer Center (BCC) is a joint venture between Sanford Health...
Click here to add this to my saved trials
720 E Rosser Ave
Bismarck, North Dakota 58501
Bismarck, North Dakota 58501
(701) 323-6741
Medcenter One Hospital Cancer Care Center Sanford Health is an integrated health system headquartered in...
Click here to add this to my saved trials
Mid Dakota Clinic, PC We're your family clinic, with the doctors you know and trust...
Click here to add this to my saved trials
900 East Broadway
Bismarck, North Dakota 58501
Bismarck, North Dakota 58501
701.530.7000
St. Alexius Medical Center Cancer Center Throughout the healing continuum we are dedicated to our...
Click here to add this to my saved trials
St. Joseph Medical Center Located in Bloomington, Illinois, OSF St. Joseph Medical Center is a...
Click here to add this to my saved trials
Boulder Community Hospital Founded in 1922 as a community-owned and operated not-for-profit hospital, Boulder Community...
Click here to add this to my saved trials
Bozeman Deaconess Cancer Center Bozeman Deaconess Cancer Center provides the latest cancer technologies and treatment...
Click here to add this to my saved trials
Fairview Ridges Hospital Fairview Ridges Hospital is a 150-bed, Level III Trauma Care facility, offering...
Click here to add this to my saved trials
St. James Healthcare Cancer Care The St. James Cancer Center is an integrated cancer treatment...
Click here to add this to my saved trials
Graham Hospital At Graham Hospital, we have a proud and rich history of serving the...
Click here to add this to my saved trials
Memorial Hospital Memorial Hospital is a vital force in establishing and maintaining the well-being of...
Click here to add this to my saved trials
Cedar Rapids Oncology Associates Oncology Associates at Mercy Medical Center in Cedar Rapids (also known...
Click here to add this to my saved trials
Cancer Center of Kansas, PA - Chanute Dr. H.E. Hynes founded Cancer Center of Kansas,...
Click here to add this to my saved trials
Adena Regional Medical Center Since 1895, Adena Health System has remained focused on its commitment...
Click here to add this to my saved trials
2222 N. Nevada Avenue
Colorado Springs, Colorado 80907
Colorado Springs, Colorado 80907
(719) 776-5000
Penrose Cancer Center at Penrose Hospital Through a full range of clinical trials, genetic counseling,...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
CCOP - Columbus As one of the original 20 CCOPs, the Columbus Community Clinical Oncology...
Click here to add this to my saved trials
Mount Carmel Health - West Hospital Located near downtown Columbus, Mount Carmel West is the...
Click here to add this to my saved trials
11850 Blackfoot St. NW
Suite 130
Coon Rapids, Minnesota 55433
Coon Rapids, Minnesota 55433
763-236-0808
Mercy and Unity Cancer Center at Mercy Hospital The Virginia Piper Cancer Institute - Mercy...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Grandview Hospital You'll feel like part of our family when you visit Grandview Medical Center...
Click here to add this to my saved trials
Samaritan North Cancer Care Center At Good Samaritan Hospital (GSH), our licensed, board-certified staff uses...
Click here to add this to my saved trials
Grady Memorial Hospital As the center of healthcare in Delaware County, Grady Memorial Hospital is...
Click here to add this to my saved trials
St. Anthony Central Hospital The St. Anthony Medical Campus in Lakewood combines our heritage of...
Click here to add this to my saved trials
Porter Adventist Hospital Founded in 1930, Porter Adventist Hospital has provided people throughout Denver and...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Rose Medical Center Well known as a Denver institution and a 9th Avenue landmark for...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
300 East Locust St., Ste 350
Des Moines, Iowa 50309
Des Moines, Iowa 50309
(515) 244-7586
CCOP - Iowa Oncology Research Association The Iowa Oncology Research Association (IORA) was established by...
Click here to add this to my saved trials
1221 Pleasant St
Des Moines, Iowa 50309
Des Moines, Iowa 50309
(515) 241-4141
John Stoddard Cancer Center at Iowa Methodist Medical Center Iowa's first children's cancer center opened...
Click here to add this to my saved trials
1221 Pleasant St Suite 100
Des Moines, Iowa 50309
Des Moines, Iowa 50309
(515) 282-2921
Medical Oncology and Hematology Associates at John Stoddard Cancer Center Iowa's first children's cancer center...
Click here to add this to my saved trials
411 Laurel St New Visions
Des Moines, Iowa 50314
Des Moines, Iowa 50314
(515) 247-3970
Medical Oncology and Hematology Associates at Mercy Cancer Center When it comes to cancer care,...
Click here to add this to my saved trials
411 Laurel Street
Des Moines, Iowa 50314
Des Moines, Iowa 50314
(515) 247-3121
Mercy Cancer Center at Mercy Medical Center - Des Moines When it comes to cancer...
Click here to add this to my saved trials
Cancer Center of Kansas, PA - Dodge City Dr. H.E. Hynes founded Cancer Center of...
Click here to add this to my saved trials
Click here to add this to my saved trials
CCOP - Duluth The Duluth CCOP, established and funded by the National Cancer Institute (NCI)...
Click here to add this to my saved trials
Miller - Dwan Medical Center Essentia Health-Duluth, located in the Miller-Dwan building, is a 165-bed...
Click here to add this to my saved trials
Fairview Southdale Hospital Fairview Health Services is an award-winning nonprofit health care system based in...
Click here to add this to my saved trials
Cancer Center of Kansas, PA - El Dorado Dr. H.E. Hynes founded Cancer Center of...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Eureka Community Hospital Eureka Community Hospital, established in 1901, offers a wide range of emergency,...
Click here to add this to my saved trials
CCOP - MeritCare Hospital The Sanford Community Cancer Consortium is a "newly" formed CCOP, merging...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Blanchard Valley Medical Associates Blanchard Valley Medical Associates was founded in 1974 by Dr. William...
Click here to add this to my saved trials
Front Range Cancer Specialists At Front Range Cancer Specialists, we are dedicated to providing quality...
Click here to add this to my saved trials
Click here to add this to my saved trials
550 Osborne Road
Fridley, Minnesota 55432
Fridley, Minnesota 55432
763-236-5000
Mercy and Unity Cancer Center at Unity Hospital Patients and their families are the heart...
Click here to add this to my saved trials
Click here to add this to my saved trials
Galesburg Clinic, PC OSF Galesburg Clinic, located on the OSF St. Mary Medical Center campus,...
Click here to add this to my saved trials
960 S. Columbia Rd.
Grand Forks, North Dakota 58201
Grand Forks, North Dakota 58201
701-780-5400
Altru Cancer Center at Altru Hospital From chemotherapy and radiation therapy to personal holistic services,...
Click here to add this to my saved trials
2635 North 7th Street
Grand Junction, Colorado 81501
Grand Junction, Colorado 81501
970-298-CARE (2273)
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center St. Mary's Hospital...
Click here to add this to my saved trials
Click here to add this to my saved trials
250 Cherry St SE
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
(616) 685-5225
Lacks Cancer Center at Saint Mary's Health Care Mercy Health Lacks Cancer Center was one...
Click here to add this to my saved trials
CCOP - Grand Rapids The Grand Rapids Clinical Oncology Program (GRCOP) is a community cancer...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
North Colorado Medical Center NCMC is a fully accredited, private, non-profit facility licensed to operate...
Click here to add this to my saved trials
Green Bay, Wisconsin 54301
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Mason District Hospital Mason District Hospital is dedicated to providing superior healthcare close to home...
Click here to add this to my saved trials
St. Peter's Hospital Welcome to St. Peter’s Hospital, providing premier health care to a five–county...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Hutchinson Area Health Care Hutchinson Health is a team of medical professionals and support staff...
Click here to add this to my saved trials
1721 S Stephenson Ave
Iron Mountain, Michigan 49801
Iron Mountain, Michigan 49801
(906) 774-1313
Dickinson County Healthcare System The vision of Dickinson County Healthcare System is to provide quality...
Click here to add this to my saved trials
Click here to add this to my saved trials
Glacier Oncology, PLLC Glacier Oncology are physician clinics focusing exclusively on the medical subspecialties of...
Click here to add this to my saved trials
Kalispell Medical Oncology at KRMC Our commitment to integrating modern treatment programs with highly-trained physicians...
Click here to add this to my saved trials
Kalispell Regional Medical Center Nestled in the beautiful Flathead Valley of Northwestern Montana, Kalispell Regional...
Click here to add this to my saved trials
Click here to add this to my saved trials
Cancer Center of Kansas, PA - Kingman Dr. H.E. Hynes founded Cancer Center of Kansas,...
Click here to add this to my saved trials