Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00887146




Registration number
NCT00887146
Ethics application status
Date submitted
22/04/2009
Date registered
23/04/2009
Date last updated
1/11/2023

Titles & IDs
Public title
Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
Scientific title
Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma
Secondary ID [1] 0 0
NCI-2011-01915
Secondary ID [2] 0 0
N0577
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain and Central Nervous System Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - concomitant temozolomide (TMZ)
Treatment: Other - radiotherapy
Treatment: Drugs - procarbazine
Treatment: Drugs - adjuvant temozolomide (TMZ)
Treatment: Drugs - CCNU
Treatment: Drugs - vincristine

Experimental: Arm A (RT, procarbazine, lomustine, vincristine) - Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm B (RT, temozolomide) - Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.


Treatment: Drugs: concomitant temozolomide (TMZ)
75 mg/m^2, orally daily

Treatment: Other: radiotherapy


Treatment: Drugs: procarbazine
Days 8-21: 60 mg/m^2 orally

Treatment: Drugs: adjuvant temozolomide (TMZ)
150 or 200 mg/m^2 orally

Treatment: Drugs: CCNU
Day 1: 110 mg/m^2 orally

Treatment: Drugs: vincristine
Days 8 and 29: 1.4 mg/m^2 IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival
Timepoint [1] 0 0
Time from study registration to time of tumor progression or death due to any cause, whichever comes first, assessed up to 16 years
Secondary outcome [1] 0 0
Time to progression
Timepoint [1] 0 0
Time from study registration to the earliest evidence of clinical progression, radiographic progression or neurocognitive progression, assessed up to 16 years
Secondary outcome [2] 0 0
Time to neurocognitive progression, assessed using the Hopkins Verbal Learning Test-Revised for Free Recall, Delayed Recall, and Delayed Recognition; the Controlled Oral Word Association test; and the Trail Making Test Part A or B
Timepoint [2] 0 0
Time from study registration to the first cognitive failure, assessed up to 16 years
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Time from study registration to time of death due to any cause, assessed up to 16 years
Secondary outcome [4] 0 0
Objective tumor response defined as a complete response or partial response
Timepoint [4] 0 0
Up to 16 years
Secondary outcome [5] 0 0
Treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Timepoint [5] 0 0
Up to 16 years

Eligibility
Key inclusion criteria
Pre-Registration

- United States (US) and Canadian sites:

* This review is mandatory prior to registration to confirm eligibility; patients must
be willing to submit tissue samples for mandatory central pathology review submission;
it should be initiated as soon after surgery as possible

- Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation
prior to submission for central path review

- Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility,
the 1p/19q analysis results will be accepted from the local site, as determined
by either a locally available or reference laboratory (for US, must be Clinical
Laboratory Improvement Act [CLIA] certified); acceptable methods for
determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by
genomic sequencing or methylomic analyses; US and Canadian sites must send a copy
of the official report to the pathology coordinator and quality assurance
specialist (QAS)

- Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic
analyses; this should be performed at the local site (US: performed in a CLIA
certified laboratory); the site must send a copy of the official report to the
pathology coordinator and QAS

Registration

- Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if
they have had a prior surgical procedure > 3 months earlier for low grade glioma, as
long as the patient has not received prior radiation or prior chemotherapy

- Histological evidence of World Health Organization (WHO) grade III anaplastic glioma
or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the
presence of an either IDH1 or IDH2, both as established by a local or referenced
laboratory qualified for the study

* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or
oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q

- Patients with codeleted low grade gliomas must also be considered "high risk" by
exhibiting one or more of the following characteristics:

- Age >= 40 and any surgical therapy

- Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than
gross total resection)

- Documented growth following prior surgery (NOTE: patients with prior surgery
cannot have received prior radiation, chemotherapy or targeted therapy)

- Intractable seizures

- Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks
prior to registration; patient must have recovered adequately from the effects of
surgery

- Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to
registration

- Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration

- Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days
prior to registration

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3
x ULN obtained =< 21 days prior to registration

- Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration

- Negative serum or urine pregnancy test done =< 7 days prior to registration, for women
of childbearing potential only

- Willingness and ability to personally complete neurocognitive testing (without
assistance) and willingness to complete the QOL testing, (either personally or with
assistance)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2

- Written informed consent

- Willingness to return to enrolling institution for follow-up during the active
monitoring phase (that is, the active treatment and observation portion) of the
study); patients who have been formally transferred to another active and approved
site participating in this study would not need to return to the enrolling institution
for this purpose

- Willingness to allow the provision of tissue samples for correlative research, as long
as adequate tissues are available; patients will not be excluded from participation in
the study, if they are willing to allow provision of tissues for the correlative
research, but there are insufficient quantities of tissue for the correlative analyses
(e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to
allow the provision of blood samples for correlative research; patients are not
excluded from participation in the study, if they are willing to provide the mandatory
biospecimens for translational/correlative research, but for logistical reasons the
specimens(s) were not obtainable or if the volume collected was insufficient

Registration
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- The following categories are ineligible:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception or contraceptive method during this study and 6 months following
the completion of chemotherapy treatments

- History of prior radiation therapy or chemotherapy for glioma; note: patients who have
a history of prior low grade glioma (with or without a distant history of prior
surgery for that glioma), but who have never received prior chemotherapy or radiation
therapy for the glioma are eligible for the study

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Concomitant serious immunocompromised status (other than that related to concomitant
steroids) that would compromise the safety of the patient on the study

- Patients known to be human immunodeficiency virus (HIV) positive and currently
receiving retroviral therapy are not eligible; note: patients known to be HIV
positive, but without clinical evidence of an immunocompromised state, are eligible
for the study

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Receiving any other investigational agent that would be considered as a treatment for
the primary neoplasm

- Other active malignancy within 5 years of registration; exceptions: non-melanotic skin
cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior
malignancy, the patient is not eligible if they are receiving other specific treatment
(with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if
they have received prior total body irradiation which included the brain

- History of myocardial infarction =< 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

- Recent history of hepatitis infection or if the treating physician determined that the
patient would be at significant risk of reactivation of hepatitis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
360
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Idaho
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kansas
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maine
Country [18] 0 0
United States of America
State/province [18] 0 0
Maryland
Country [19] 0 0
United States of America
State/province [19] 0 0
Massachusetts
Country [20] 0 0
United States of America
State/province [20] 0 0
Michigan
Country [21] 0 0
United States of America
State/province [21] 0 0
Minnesota
Country [22] 0 0
United States of America
State/province [22] 0 0
Missouri
Country [23] 0 0
United States of America
State/province [23] 0 0
Montana
Country [24] 0 0
United States of America
State/province [24] 0 0
Nebraska
Country [25] 0 0
United States of America
State/province [25] 0 0
Nevada
Country [26] 0 0
United States of America
State/province [26] 0 0
New Hampshire
Country [27] 0 0
United States of America
State/province [27] 0 0
New Jersey
Country [28] 0 0
United States of America
State/province [28] 0 0
New Mexico
Country [29] 0 0
United States of America
State/province [29] 0 0
New York
Country [30] 0 0
United States of America
State/province [30] 0 0
North Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
North Dakota
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
State/province [33] 0 0
Oklahoma
Country [34] 0 0
United States of America
State/province [34] 0 0
Oregon
Country [35] 0 0
United States of America
State/province [35] 0 0
Pennsylvania
Country [36] 0 0
United States of America
State/province [36] 0 0
South Carolina
Country [37] 0 0
United States of America
State/province [37] 0 0
South Dakota
Country [38] 0 0
United States of America
State/province [38] 0 0
Tennessee
Country [39] 0 0
United States of America
State/province [39] 0 0
Texas
Country [40] 0 0
United States of America
State/province [40] 0 0
Utah
Country [41] 0 0
United States of America
State/province [41] 0 0
Vermont
Country [42] 0 0
United States of America
State/province [42] 0 0
Virginia
Country [43] 0 0
United States of America
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Washington
Country [44] 0 0
United States of America
State/province [44] 0 0
West Virginia
Country [45] 0 0
United States of America
State/province [45] 0 0
Wisconsin
Country [46] 0 0
Austria
State/province [46] 0 0
Vienna
Country [47] 0 0
Belgium
State/province [47] 0 0
Antwerpen
Country [48] 0 0
Canada
State/province [48] 0 0
Alberta
Country [49] 0 0
Canada
State/province [49] 0 0
British Columbia
Country [50] 0 0
Canada
State/province [50] 0 0
Manitoba
Country [51] 0 0
Canada
State/province [51] 0 0
Ontario
Country [52] 0 0
Canada
State/province [52] 0 0
Quebec
Country [53] 0 0
Canada
State/province [53] 0 0
Saskatchewan
Country [54] 0 0
France
State/province [54] 0 0
Lyon
Country [55] 0 0
France
State/province [55] 0 0
Nice
Country [56] 0 0
France
State/province [56] 0 0
Villejuif
Country [57] 0 0
Netherlands
State/province [57] 0 0
Amsterdam
Country [58] 0 0
Netherlands
State/province [58] 0 0
Groningen
Country [59] 0 0
Netherlands
State/province [59] 0 0
Maastricht
Country [60] 0 0
Netherlands
State/province [60] 0 0
Rotterdam

Funding & Sponsors
Primary sponsor type
Other
Name
Alliance for Clinical Trials in Oncology
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
European Organisation for Research and Treatment Center (EORTC)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Canadian Cancer Trials Group
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Radiation therapy uses high-energy x-rays to kill tumor cells. 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 giving
radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is
more effective in treating anaplastic glioma or low grade glioma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00887146
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Kurt Jaeckle, MD
Address 0 0
Mayo Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kurt Jaeckle, MD
Address 0 0
Country 0 0
Phone 0 0
904-953-7102
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00887146