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NCT00884741

Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma

Completed Phase 3 Results posted Last updated 24 July 2019
What this trial tests

Phase 3 trial testing 3-Dimensional Conformal Radiation Therapy in Glioblastoma in 637 participants. Completed in 17 March 2013.

Timeline
15 April 2009
Primary endpoint
17 March 2013
17 March 2013

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment637
Start date15 April 2009
Primary completion17 March 2013
Estimated completion17 March 2013
Sites330 locations across Canada, United States, Israel

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Glioblastoma or Gliosarcoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Primary · From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.

Survival time was defined as time from randomization to date of death from any cause and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.

GroupValue95% CI
Randomized Arm 1: TMZ+RT + Placebo16.114.8 – 18.7
Randomized Arm 2: TMZ+RT + Bevacizumab15.714.2 – 16.8
Progression-free Survival (PFS) Primary · From randomization to date of progression, death, or last follow-up for progression-free survival. Analysis occurs after all 390 deaths have been reported.

Progression-free survival was defined as time from randomization to date of progression, death, or last follow-up, and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.

GroupValue95% CI
Randomized Arm 1: TMZ+RT + Placebo7.35.6 – 7.9
Randomized Arm 2: TMZ+RT + Bevacizumab10.710.0 – 12.2
Incidence of Grade 3 and Higher Treatment-related Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 3.0 Secondary · Up to 30 days

AEs are graded by using CTCAE 3.0. The difference between the two randomized arms in the percentage of patients with grade 3 or higher toxicities reported as possibly/probably/definitely related to protocol treatment will be tested using a chi square test.

GroupValue95% CI
Randomized Arm 1: TMZ+RT + Placebo87
Randomized Arm 2: TMZ+RT + Bevacizumab97

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pre-Randomization TMZ+RT
Serious: 5/10 (50%)
Deaths:
Randomized Arm 1: TMZ+RT + Placebo
Serious: 115/300 (38%)
Deaths:
Randomized Arm 2: TMZ+RT + Bevacizumab
Serious: 141/303 (47%)
Deaths:

Serious adverse events (177 terms)

ReactionSystemPre-Randomization TMZ+RTRandomized Arm 1: TMZ+RT +…Randomized Arm 2: TMZ+RT +…
Platelet count decreasedInvestigations
SeizureNervous system disorders
ThrombosisVascular disorders
FatigueGeneral disorders
Neutrophil count decreasedInvestigations
Muscle weaknessMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
ConfusionPsychiatric disorders
Hemoglobin decreasedBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
DeathGeneral disorders
AnorexiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Speech disorderNervous system disorders
ConstipationGastrointestinal disorders
Ischemia cerebrovascularNervous system disorders
LeukopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Wound dehiscenceInjury, poisoning and procedural complications
AtaxiaNervous system disorders
Peripheral motor neuropathyNervous system disorders
Colonic perforationGastrointestinal disorders
Other adverse events (94 terms — click to expand)

ReactionSystemPre-Randomization TMZ+RTRandomized Arm 1: TMZ+RT +…Randomized Arm 2: TMZ+RT +…
FatigueGeneral disorders
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Hemoglobin decreasedBlood and lymphatic system disorders
HyperglycemiaMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
VomitingGastrointestinal disorders
DizzinessNervous system disorders
InsomniaPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
Memory impairmentNervous system disorders
HypertensionVascular disorders
DiarrheaGastrointestinal disorders
SeizureNervous system disorders
Platelet count decreasedInvestigations
Muscle weaknessMusculoskeletal and connective tissue disorders
Speech disorderNervous system disorders
Weight lossInvestigations
HypocalcemiaMetabolism and nutrition disorders
Taste alterationNervous system disorders
DepressionPsychiatric disorders
HypoalbuminemiaMetabolism and nutrition disorders
Joint painMusculoskeletal and connective tissue disorders
Peripheral sensory neuropathyNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
Dermatitis radiationInjury, poisoning and procedural complications
Vision blurredEye disorders
Radiation recall reaction (dermatologic)Injury, poisoning and procedural complications
HypokalemiaMetabolism and nutrition disorders
AtaxiaNervous system disorders
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Platelet count decreased, Seizure, Thrombosis, Fatigue, Neutrophil count decreased, Muscle weakness, Nausea, Platelet count decreased.

Data from ClinicalTrials.gov NCT00884741 adverse events section.

Sponsor's own description

This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A randomized trial of bevacizumab for newly diagnosed glioblastoma.
    Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, et al · · 2014 · cited 2073× · PMID 24552317 · DOI 10.1056/nejmoa1308573
  2. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.
    Wen PY, Weller M, Lee EQ, Alexander BM, et al · · 2020 · cited 908× · PMID 32328653 · DOI 10.1093/neuonc/noaa106
  3. Glioma targeted therapy: insight into future of molecular approaches.
    Yang K, Wu Z, Zhang H, Zhang N, et al · · 2022 · cited 518× · PMID 35135556 · DOI 10.1186/s12943-022-01513-z
  4. Emerging therapies for glioblastoma: current state and future directions.
    Rong L, Li N, Zhang Z. · · 2022 · cited 351× · PMID 35428347 · DOI 10.1186/s13046-022-02349-7
  5. Federated learning enables big data for rare cancer boundary detection.
    Pati S, Baid U, Edwards B, Sheller M, et al · · 2022 · cited 183× · PMID 36470898 · DOI 10.1038/s41467-022-33407-5
  6. Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma.
    Happold C, Gorlia T, Chinot O, Gilbert MR, et al · · 2016 · cited 156× · PMID 26786929 · DOI 10.1200/jco.2015.63.6563
  7. Barriers to Radiation-Induced <i>In Situ</i> Tumor Vaccination.
    Wennerberg E, Lhuillier C, Vanpouille-Box C, Pilones KA, et al · · 2017 · cited 150× · PMID 28348554 · DOI 10.3389/fimmu.2017.00229
  8. Glioblastoma Therapy: Past, Present and Future.
    Obrador E, Moreno-Murciano P, Oriol-Caballo M, López-Blanch R, et al · · 2024 · cited 147× · PMID 38473776 · DOI 10.3390/ijms25052529

Verify or expand the search:

Other trials of 3-Dimensional Conformal Radiation Therapy

Trials testing the same drug.

Other recruiting trials for Glioblastoma

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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