Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00978458

Collaborator

National Cancer Institute (NCI) (NIH)

540

Enrollment

168

Locations

Arms

207.6

Anticipated Duration (Months)

3.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. 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. It is not yet known whether radiation therapy is more effective when given together with or without temozolomide in treating patients with low-grade glioma.

PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it works when given together with or without temozolomide in treating patients with low-grade glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Neurotoxicity	Drug: temozolomide Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Primary

To determine whether the addition of temozolomide to fractionated radiotherapy improves the progression-free survival (PFS) of patients with symptomatic or progressive low-grade gliomas.
To determine whether the addition of temozolomide to fractionated radiotherapy improves the median overall survival (OS) of these patients.

Secondary

To determine whether combination therapy with temozolomide and radiotherapy improves or maintains cognition and quality of life compared to radiotherapy alone.
To compare the toxicities (severe or worse [≥ grade 3]) of radiotherapy with vs without temozolomide in these patients.
To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS.
To determine the impact of 1p and 19q status on PFS and OS of patients treated with temozolomide.
To create a tumor and tissue bank, including plasma and germ line DNA, within the ECOG Pathology Coordinating Office.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 40 years vs ≥ 40 years), 1p and 19q status (both deleted vs either/both intact vs undeterminable), pre-operative maximum tumor diameter (< 6 cm vs ≥ 6 cm [based on T2 or FLAIR MRI]), Karnofsky performance status (60-70% vs 80-100%), and contrast enhancement on pre-treatment MRI scan (present vs absent). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).
Arm II: Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo quality-of-life and neurocognitive (e.g., visual scanning speed, divided attention, language, memory, and fine motor skills) assessments at baseline, annually until disease progression, and at the time of disease progression.

Tumor tissue samples are collected at baseline for confirmation of diagnosis and determination of 1p and 19q deletion status. Peripheral blood, serum, and additional tumor tissue samples may be collected for further research studies.

After completion of study treatment, patients are followed up periodically for up to 15 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

540 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

Official Title:

Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas

Actual Study Start Date :

Sep 11, 2009

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).	Radiation: 3-dimensional conformal radiation therapy Given once daily 5 days a week for 5½ weeks Radiation: intensity-modulated radiation therapy Given once daily 5 days a week for 5½ weeks
Experimental: Arm II Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: temozolomide Given orally Radiation: 3-dimensional conformal radiation therapy Given once daily 5 days a week for 5½ weeks Radiation: intensity-modulated radiation therapy Given once daily 5 days a week for 5½ weeks

Arm

Intervention/Treatment

Active Comparator: Arm I

Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).

Radiation: 3-dimensional conformal radiation therapy

Given once daily 5 days a week for 5½ weeks

Radiation: intensity-modulated radiation therapy

Given once daily 5 days a week for 5½ weeks

Experimental: Arm II

Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: temozolomide

Given orally

Radiation: 3-dimensional conformal radiation therapy

Given once daily 5 days a week for 5½ weeks

Radiation: intensity-modulated radiation therapy

Given once daily 5 days a week for 5½ weeks

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) []
Overall survival (OS) []

Secondary Outcome Measures

Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression []
Neurocognitive functioning as assessed at baseline, annually until disease progression, and at the time of disease progression []
Correlation of pre-treatment 1p and 19q levels in tumor tissue samples with PFS and OS []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed* supratentorial low-grade glioma, including 1 of the following:
Grade 2 astrocytoma
Grade 2 oligodendroglioma
Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma)
NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma must be the most recent pathological diagnosis; no pathological diagnosis of grade 3 or 4 glioma at any time
Paraffin-embedded tumor specimen available for submission for confirmation of pathological review and determination of 1p and 19q deletion status
Patients must currently meet ≥ 1 of the following criteria*:
Uncontrolled symptoms, defined as any of the following:
Headaches associated with mass effect
Uncontrolled seizures despite two different antiepileptic drug regimens (i.e., two antiepileptic drugs tested either sequentially or in combination)
Focal neurological symptoms
Cognitive symptoms or deficits
Tumor progression by serial MRIs, defined as any of the following:
New or progressive enhancement
New or progressive T2 or FLAIR signal abnormality
Age ≥ 40 years
NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures that are well-controlled on antiepileptic drugs AND who have no evidence of radiographic progression are not eligible.
Patients who have undergone gross total resection and have no detectable residual disease are eligible
No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or dysembryoplastic neuroepithelial tumors

PATIENT CHARACTERISTICS:

Karnofsky performance status 60-100%
WBC ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hematocrit ≥ 30%
Bilirubin ≤ 2 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Creatinine ≤ 2.0 times ULN
Not pregnant or nursing
Negative pregnancy test
Able to undergo MRI with and without contrast
No other malignancy within the past 5 years, except for nonmelanoma skin cancer or cervical carcinoma in situ
No uncontrolled infection
No known HIV positivity
No medical disorder that would increase risks associated with radiotherapy and temozolomide
No other disorder that would limit life expectancy to < 5 years

PRIOR CONCURRENT THERAPY:

No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational therapy directed at the brain tumor
Any number of prior surgical procedures for the brain tumor allowed
No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the brain
At least 2 weeks since any prior brain surgery (e.g., stereotatic biopsy, open biopsy, or resection)
At least 6 weeks since prior MRI and chest x-ray
If resection is performed, an MRI after surgery is required

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	Arizona Oncology Services Foundation	Phoenix	Arizona	United States	85013
3	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
4	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California	United States	92868
5	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
6	St. Anthony Central Hospital	Denver	Colorado	United States	80204
7	Porter Adventist Hospital	Denver	Colorado	United States	80210
8	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
9	St. Joseph Hospital	Denver	Colorado	United States	80218
10	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80222
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
13	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
14	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
15	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
16	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
17	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
18	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
19	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
20	Graham Hospital	Canton	Illinois	United States	61520
21	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
22	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
23	Memorial Hospital	Carthage	Illinois	United States	62321
24	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
25	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-3785
26	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
27	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
28	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
29	Eureka Community Hospital	Eureka	Illinois	United States	61530
30	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
31	Evanston Hospital	Evanston	Illinois	United States	60201-1781
32	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
33	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
34	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
35	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
36	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
37	McDonough District Hospital	Macomb	Illinois	United States	61455
38	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
39	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
40	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
41	Community Cancer Center	Normal	Illinois	United States	61761
42	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
43	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
44	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
45	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
46	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
47	Proctor Hospital	Peoria	Illinois	United States	61614
48	OSF St. Francis Medical Center	Peoria	Illinois	United States	61615-7827
49	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
50	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
51	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
52	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
53	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
54	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
55	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
56	Valley Cancer Center	Spring Valley	Illinois	United States	61362
57	Elkhart General Hospital	Elkhart	Indiana	United States	46515
58	Radiation Oncology Associates Southwest	Fort Wayne	Indiana	United States	46804
59	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana	United States	46805
60	Community Regional Cancer Care at Community Hospital East	Indianapolis	Indiana	United States	46219
61	Community Regional Cancer Care at Community Hospital North	Indianapolis	Indiana	United States	46256
62	Howard Community Hospital	Kokomo	Indiana	United States	46904
63	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
64	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
65	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
66	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
67	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
68	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
69	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
70	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
71	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
72	CCOP - Wichita	Wichita	Kansas	United States	67214
73	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
74	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
75	Louisville Oncology at Norton Cancer Institute - Louisville	Louisville	Kentucky	United States	40202
76	Norton Suburban Hospital	Louisville	Kentucky	United States	40207
77	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine	United States	04074
78	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
79	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
80	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
81	Hurley Medical Center	Flint	Michigan	United States	48503
82	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
83	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
84	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
85	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
86	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
87	CCOP - Duluth	Duluth	Minnesota	United States	55805
88	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
89	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
90	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
91	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
92	Minnesota Oncology - Maplewood	Maplewood	Minnesota	United States	55109
93	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
94	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
95	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
96	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
97	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
98	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
99	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
100	United Hospital	Saint Paul	Minnesota	United States	55102
101	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
102	Lakeview Hospital	Stillwater	Minnesota	United States	55082
103	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
104	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
105	Minnesota Oncology - Woodbury	Woodbury	Minnesota	United States	55125
106	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
107	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
108	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
109	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
110	Nebraska Medical Center	Omaha	Nebraska	United States	68198
111	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
112	New York Oncology Hematology, PC at Albany Medical Center	Albany	New York	United States	12208
113	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
114	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
115	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
116	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
117	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
118	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
119	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
120	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
121	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
122	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
123	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
124	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
125	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
126	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania	United States	18015
127	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
128	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
129	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina	United States	29605
130	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina	United States	29605
131	Cancer Centers of the Carolinas - Eastside	Greenville	South Carolina	United States	29615
132	CCOP - Greenville	Greenville	South Carolina	United States	29615
133	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina	United States	29650
134	Cancer Centers of the Carolinas - Greer Radiation Oncology	Greer	South Carolina	United States	29650
135	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina	United States	29672
136	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
137	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
138	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina	United States	29307
139	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
140	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
141	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
142	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
143	University of Texas Medical Branch	Galveston	Texas	United States	77555-0361
144	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
145	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
146	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
147	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
148	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
149	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
150	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
151	Legacy Salmon Creek Medical Center	Vancouver	Washington	United States	98686
152	Theda Care Cancer Institute	Appleton	Wisconsin	United States	54911
153	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
154	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
155	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
156	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
157	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
158	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
159	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin	United States	53097
160	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin	United States	53211
161	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
162	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
163	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
164	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
165	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
166	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188
167	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
168	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476