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

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00521001
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 49
• Locations: 198
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Drug: everolimus; Drug: temozolomide	Phase 2

Detailed 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.

• Evaluate confirmed response rate.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: everolimus + temozolomide 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.

Drug: everolimus; Drug: temozolomide

Outcome Measures

Primary Outcome Measures

1. 9-week Progression-free Survival Rate [at 9 weeks]

   The primary endpoint of this trial is the 9 week PFS rate. A patient is a success if they are progression free at their cycle 2 evaluation (approximately 9 weeks post registration). All patients, who meet the eligibility criteria, sign a consent form, and start treatment will be included in the evaluation of the 9-week PFS rate (evaluable patients). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. If some patients are lost to follow up prior to their cycle 2 evaluation, the Kaplan-Meier method will be used to estimate the 9 week PFS rate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Survival Time [Time from registration to death due to any cause; Up to 5 years]

   Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

2. Time to Disease Progression [Time from registration to the earliest date documentation of disease progression; Up to 5 years]

   Time to disease progression is defined as the time from registration to the earliest date documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

3. Confirmed Response Rate (Complete Response and Partial Response) [Up to 5 years]

   Confirmed response rates will be evaluated by dividing the number of confirmed responders (i.e. patients that achieve a CR or PR on consecutive evaluations) by the total number of evaluable patients. Confidence intervals for the true response rate will be calculated using the properties of the binomial distribution.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
2	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
3	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
4	St. Anthony Central Hospital	Denver	Colorado	United States	80204
5	Porter Adventist Hospital	Denver	Colorado	United States	80210
6	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
7	St. Joseph Hospital	Denver	Colorado	United States	80218
8	Rose Medical Center	Denver	Colorado	United States	80220
9	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
10	Swedish Medical Center	Englewood	Colorado	United States	80110
11	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
12	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
13	North Colorado Medical Center	Greeley	Colorado	United States	80631
14	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
15	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80502
16	McKee Medical Center	Loveland	Colorado	United States	80539
17	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
18	North Suburban Medical Center	Thornton	Colorado	United States	80229
19	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
20	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
21	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
22	Graham Hospital	Canton	Illinois	United States	61520
23	Memorial Hospital	Carthage	Illinois	United States	62321
24	Eureka Community Hospital	Eureka	Illinois	United States	61530
25	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
26	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
27	Mason District Hospital	Havana	Illinois	United States	62644
28	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
29	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
30	McDonough District Hospital	Macomb	Illinois	United States	61455
31	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
32	Community Cancer Center	Normal	Illinois	United States	61761
33	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
34	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
35	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
36	Proctor Hospital	Peoria	Illinois	United States	61614
37	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
38	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
39	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
40	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
41	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
42	Perry Memorial Hospital	Princeton	Illinois	United States	61356
43	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
44	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
45	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
46	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
47	Elkhart General Hospital	Elkhart	Indiana	United States	46515
48	Howard Community Hospital	Kokomo	Indiana	United States	46904
49	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
50	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
51	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
52	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
53	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
54	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
55	South Bend Clinic	South Bend	Indiana	United States	46617
56	McFarland Clinic, PC	Ames	Iowa	United States	50010
57	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
58	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
59	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
60	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
61	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
62	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
63	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
64	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
65	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
66	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
67	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
68	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
69	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
70	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
71	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
72	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
73	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
74	Southwest Medical Center	Liberal	Kansas	United States	67901
75	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
76	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
77	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
78	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
79	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
80	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
81	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
82	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
83	CCOP - Wichita	Wichita	Kansas	United States	67214
84	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
85	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
86	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
87	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
88	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
89	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
90	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
91	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
92	Holland Community Hospital	Holland	Michigan	United States	49423
93	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
94	Hackley Hospital	Muskegon	Michigan	United States	49442
95	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
96	Munson Medical Center	Traverse City	Michigan	United States	49684
97	Metro Health Hospital	Wyoming	Michigan	United States	49519
98		Alexandria	Minnesota	United States	56308
99	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
100	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
101	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
102	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
103	CCOP - Duluth	Duluth	Minnesota	United States	55805
104	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
105	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
106		Fergus Falls	Minnesota	United States	56537
107	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
108	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
109	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
110	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
111	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
112	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
113	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
114	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
115	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
116	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
117	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
118	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
119	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
120	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
121	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
122	United Hospital	Saint Paul	Minnesota	United States	55102
123	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
124	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
125	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
126	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
127	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
128	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
129	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
130	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
131	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
132	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
133	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
134	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
135		Great Falls	Montana	United States	59405
136	St. Peter's Hospital	Helena	Montana	United States	59601
137	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
138	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
139	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
140	Community Medical Center	Missoula	Montana	United States	59801
141	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
142	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
143	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
144	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
145	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
146	Immanuel Medical Center	Omaha	Nebraska	United States	68122
147	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
148	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
149	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
150	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
151	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
152	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
153	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
154	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
155	MeritCare Broadway	Fargo	North Dakota	United States	58122
156	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
157	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
158	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
159	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
160	CCOP - Columbus	Columbus	Ohio	United States	43215
161	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
162	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
163	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
164	Grandview Hospital	Dayton	Ohio	United States	45405
165	Good Samaritan Hospital	Dayton	Ohio	United States	45406
166	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
167	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
168	CCOP - Dayton	Dayton	Ohio	United States	45429
169	Grady Memorial Hospital	Delaware	Ohio	United States	43015
170	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
171	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
172	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
173	Fairfield Medical Center	Lancaster	Ohio	United States	43130
174	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
175	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
176	Mercy Medical Center	Springfield	Ohio	United States	45504
177	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
178	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
179	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
180	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
181	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
182	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
183	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
184	AnMed Cancer Center	Anderson	South Carolina	United States	29621
185	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
186	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
187	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
188	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
189	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
190	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
191	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
192	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
193	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
194	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
195	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
196	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
197	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
198	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Ravi D. Rao, MD, MBBS, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00521001
• Other Study ID Numbers: NCCTG-N0675; NCI-2012-02713; CDR0000562166
• First Posted: Aug 27, 2007
• Last Update Posted: Aug 14, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: stage IV melanoma
• Additional relevant MeSH terms: Melanoma; Everolimus; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	49
COMPLETED	48
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	48
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	16 33.3%
Male	32 66.7%
Region of Enrollment (Count of Participants)
United States	48 100%

Outcome Measures

1. Primary Outcome

Title	9-week Progression-free Survival Rate
Description	The primary endpoint of this trial is the 9 week PFS rate. A patient is a success if they are progression free at their cycle 2 evaluation (approximately 9 weeks post registration). All patients, who meet the eligibility criteria, sign a consent form, and start treatment will be included in the evaluation of the 9-week PFS rate (evaluable patients). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. If some patients are lost to follow up prior to their cycle 2 evaluation, the Kaplan-Meier method will be used to estimate the 9 week PFS rate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	at 9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	48
Number (95% Confidence Interval) [proportion of patients]	0.44

2. Secondary Outcome

Title	Survival Time
Description	Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time Frame	Time from registration to death due to any cause; Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	48
Median (95% Confidence Interval) [months]	8.6

3. Secondary Outcome

Title	Time to Disease Progression
Description	Time to disease progression is defined as the time from registration to the earliest date documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Time from registration to the earliest date documentation of disease progression; Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	48
Median (95% Confidence Interval) [months]	2.4

4. Secondary Outcome

Title	Confirmed Response Rate (Complete Response and Partial Response)
Description	Confirmed response rates will be evaluated by dividing the number of confirmed responders (i.e. patients that achieve a CR or PR on consecutive evaluations) by the total number of evaluable patients. Confidence intervals for the true response rate will be calculated using the properties of the binomial distribution.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	48
Number (95% Confidence Interval) [percentage of confirmed responses]	8.3

Adverse Events

Time Frame	Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years.
Adverse Event Reporting Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Arm/Group Title	Everolimus + Temozolomide
Arm/Group Description	Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Everolimus + Temozolomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Everolimus + Temozolomide
	Affected / at Risk (%)	# Events
Total	6/48 (12.5%)
Cardiac disorders
Palpitations	1/48 (2.1%)	1
Gastrointestinal disorders
Ear, nose and throat examination abnormal	1/48 (2.1%)	1
General disorders
Death	1/48 (2.1%)	1
Fatigue	1/48 (2.1%)	3
Immune system disorders
Hypersensitivity	1/48 (2.1%)	1
Infections and infestations
Skin infection	1/48 (2.1%)	1
Investigations
Leukocyte count decreased	3/48 (6.3%)	3
Lymphocyte count decreased	2/48 (4.2%)	3
Neutrophil count decreased	4/48 (8.3%)	4
Platelet count decreased	5/48 (10.4%)	5
Metabolism and nutrition disorders
Anorexia	1/48 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/48 (2.1%)	2
Hypoxia	1/48 (2.1%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	1/48 (2.1%)	1
Other (Not Including Serious) Adverse Events
	Everolimus + Temozolomide
	Affected / at Risk (%)	# Events
Total	48/48 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	8/48 (16.7%)	14
Gastrointestinal disorders
Abdominal pain	1/48 (2.1%)	1
Constipation	5/48 (10.4%)	6
Diarrhea	7/48 (14.6%)	8
Ear, nose and throat examination abnormal	19/48 (39.6%)	27
Nausea	27/48 (56.3%)	40
Vomiting	13/48 (27.1%)	16
General disorders
Disease progression	1/48 (2.1%)	1
Fatigue	39/48 (81.3%)	116
Investigations
Alanine aminotransferase increased	1/48 (2.1%)	2
Aspartate aminotransferase increased	1/48 (2.1%)	1
Bilirubin increased	1/48 (2.1%)	1
Creatinine increased	1/48 (2.1%)	2
Leukocyte count decreased	31/48 (64.6%)	90
Lymphocyte count decreased	27/48 (56.3%)	101
Neutrophil count decreased	22/48 (45.8%)	43
Platelet count decreased	21/48 (43.8%)	58
Serum cholesterol increased	4/48 (8.3%)	8
Weight loss	1/48 (2.1%)	1
Metabolism and nutrition disorders
Anorexia	21/48 (43.8%)	39
Blood glucose increased	3/48 (6.3%)	6
Serum albumin decreased	1/48 (2.1%)	1
Serum calcium decreased	1/48 (2.1%)	1
Serum calcium increased	1/48 (2.1%)	1
Serum potassium decreased	1/48 (2.1%)	1
Serum potassium increased	1/48 (2.1%)	1
Serum sodium decreased	1/48 (2.1%)	1
Serum triglycerides increased	3/48 (6.3%)	3
Musculoskeletal and connective tissue disorders
Back pain	3/48 (6.3%)	3
Joint pain	3/48 (6.3%)	5
Muscle weakness	1/48 (2.1%)	1
Muscle weakness left-sided	1/48 (2.1%)	1
Muscle weakness lower limb	1/48 (2.1%)	1
Myalgia	3/48 (6.3%)	3
Pain in extremity	2/48 (4.2%)	2
Nervous system disorders
Dizziness	2/48 (4.2%)	2
Facial nerve disorder	1/48 (2.1%)	1
Headache	14/48 (29.2%)	22
Taste alteration	2/48 (4.2%)	2
Psychiatric disorders
Agitation	1/48 (2.1%)	1
Anxiety	3/48 (6.3%)	3
Depression	1/48 (2.1%)	1
Insomnia	1/48 (2.1%)	1
Renal and urinary disorders
Cystitis	1/48 (2.1%)	1
Urinary frequency	1/48 (2.1%)	2
Reproductive system and breast disorders
Pelvic pain	1/48 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/48 (2.1%)	1
Dyspnea	2/48 (4.2%)	3
Pneumonitis	6/48 (12.5%)	20
Skin and subcutaneous tissue disorders
Body odor	1/48 (2.1%)	1
Erythema multiforme	1/48 (2.1%)	1
Rash acneiform	1/48 (2.1%)	1
Rash desquamating	2/48 (4.2%)	2
Urticaria	1/48 (2.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.