NCT00887146|Active Not RecruitingPhase 3DMC

Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma

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

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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5 other identifiers

N0577NCI-2011-01915EORTC-26081-22086EudraCT-2008-007295-14CDR0000640442

Study Type

interventional

Target

305

Locations

6 countries

Sites

291

Timeline

RegisteredApr 2009

StartedSep 2009

CompletionOct 2029

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 Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

305

participants targeted

Target at P50-P75 for phase_3

Timeline

43mo left

Started Sep 2009

Longer than P75 for phase_3

Geographic Reach

6 countries

291 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

20.2 years study duration

Study Progress83%

Sep 2009Oct 2029

First Submitted

Initial submission to the registry

April 22, 2009

Completed

1 day until next milestone

First Posted

Study publicly available on registry

April 23, 2009

Completed

4 months until next milestone

Study Start

First participant enrolled

September 1, 2009

Completed

20.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2029

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2029

Last Updated

January 22, 2026

Status Verified

January 1, 2026

Enrollment Period

20.2 years

First QC Date

April 22, 2009

Last Update Submit

January 20, 2026

Conditions

Brain and Central Nervous System Tumors

Keywords

adult anaplastic astrocytomaadult anaplastic oligodendrogliomaadult mixed glioma

Outcome Measures

Primary Outcomes (1)

Progression-free survival
The distribution of progression free survival for Arms A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median progression free survival (PFS) will be estimated with their confidence intervals. The Cox proportional hazards model will be used to assess whether the distributions of progression survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and performance score). Both non-inferiority and superiority will be tested in this trial for the primary goal and no multiple-comparison adjustment will be considered.
Time from study registration to time of tumor progression or death due to any cause, whichever comes first, assessed up to 16 years

Secondary Outcomes (5)

Time to progression
Time from study registration to the earliest evidence of clinical progression, radiographic progression or neurocognitive progression, assessed up to 16 years
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
Time from study registration to the first cognitive failure, assessed up to 16 years
Overall survival
Time from study registration to time of death due to any cause, assessed up to 16 years
Objective tumor response defined as a complete response or partial response
Up to 16 years
Treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Up to 16 years

Study Arms (2)

Arm A (RT, procarbazine, lomustine, vincristine)

EXPERIMENTAL

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.

Radiation: radiotherapyDrug: procarbazineDrug: CCNUDrug: vincristine

Arm B (RT, temozolomide)

EXPERIMENTAL

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.

Drug: concomitant temozolomide (TMZ)Radiation: radiotherapyDrug: adjuvant temozolomide (TMZ)

Interventions

concomitant temozolomide (TMZ)DRUG

75 mg/m\^2, orally daily

Arm B (RT, temozolomide)

radiotherapyRADIATION

Arm A (RT, procarbazine, lomustine, vincristine)Arm B (RT, temozolomide)

procarbazineDRUG

Days 8-21: 60 mg/m\^2 orally

Arm A (RT, procarbazine, lomustine, vincristine)

adjuvant temozolomide (TMZ)DRUG

150 or 200 mg/m\^2 orally

Arm B (RT, temozolomide)

CCNUDRUG

Day 1: 110 mg/m\^2 orally

Arm A (RT, procarbazine, lomustine, vincristine)

vincristineDRUG

Days 8 and 29: 1.4 mg/m\^2 IV

Arm A (RT, procarbazine, lomustine, vincristine)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
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
+11 more criteria

You may not qualify if:

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
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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator
European Organisation for Research and Treatment Center (EORTC)collaborator
Canadian Cancer Trials Groupcollaborator

Study Sites (291)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Providence Hospital

Mobile, Alabama, 36608, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Alaska Oncology and Hematology LLC