Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

For patients with glioblastoma (World Health Organization grade IV), the cure rate is very low with standard local treatment. These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. (Refer to the Glioblastoma section in the Classification section of this summary for more information.) Age may not be a survival factor. Rrecent reviews and case studies have shown equal survival for patients over 65 years old if treated regardless of age.[1-4]

Standard treatment options:

1. Surgery plus radiation therapy.

   Patients with glioblastoma multiforme aged 70 to 85 years were randomly assigned in a clinical trial (PHRC) to receive radiation therapy plus supportive care or supportive care only. Surgical resection was attempted in all patients, and the extent of surgery was the same in both groups. A survival benefit of 12.2 weeks was seen in the combined treatment group.[5] The 21-week follow-up showed a median survival of 29.1 weeks for the 39 patients who received radiation therapy plus supportive care and 16.9 weeks for the 42 patients who received only supportive care. The hazard ratio of death in the radiation therapy arm was 0.47 (95% confidence interval [CI], 0.29–0.76; P = .002).[5][Level of evidence: 1iiA]

   A randomized study of patients 60 years and older compared 60 Gy administered over the course of 6 weeks (standard course) with 40 Gy in 15 fractions administered over the course of 3 weeks (short course).[6] Karnofsky performance status scores were similar. Overall survival (OS) was similar in the two groups in this underpowered study (lower-bound 95% CI, -13.7%).[6][Level of evidence: 1iiA]




2. Surgery plus radiation therapy and chemotherapy.[7-11]

   A randomized cooperative study showed no additional benefit from brachytherapy added to external-beam radiation therapy (EBRT) and carmustine (BCNU).[12][Level of evidence: 1iiA]




3. BCNU-impregnated polymer (Gliadel wafer) implanted during initial surgery.

   A randomized double-blinded controlled trial with 240 patients with high-grade glioma showed a survival advantage for patients who had BCNU-impregnated polymer placed intraoperatively at the time of initial surgery when they were compared with the placebo-treated group. The median survival was 13.9 months in the treated group and 11.6 months in the control group (OS, P = .03).[13][Level of evidence: 1iA]




4. Radiation therapy and concurrent chemotherapy.

   A randomized study (European Organization for the Research and Treatment of Cancer [EORTC-26981]) of radiation therapy versus radiation therapy plus temozolomide followed by 6 months of adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme demonstrated a statistically significant increase in median survival of 3 months in the combination-treated group.[14] The 2-year survival rate was 26.5% in the combination group compared with only 10.4% in the radiation-only group. The treatment is relatively safe and well tolerated.[14-18][Level of evidence: 1iiA]

Treatment options under clinical evaluation:

• Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate hyperfractionated radiation therapy, accelerated-fraction radiation therapy, stereotactic radiosurgery, radiosensitizers, hyperthermia, interstitial brachytherapy, or intraoperative radiation therapy used in conjunction with EBRT to improve local control of the tumor. These patients are also candidates for studies that evaluate new drugs and biological response modifiers following radiation therapy.[19-22] Cooperative groups have evaluated new treatment options as evidenced in the RTOG-9803, RTOG-0211, RTOG-BR-0023, and RTOG-BR-0013 trials.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with adult glioblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Filippini G, Falcone C, Boiardi A, et al.: Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma. Neuro Oncol 10 (1): 79-87, 2008.  [PUBMED Abstract]
   
   
2. Chiocca EA: Being old is no fun: treatment of glioblastoma multiforme in the elderly. J Neurosurg 108 (4): 639-40, 2008.  [PUBMED Abstract]
   
   
3. Barnholtz-Sloan JS, Williams VL, Maldonado JL, et al.: Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma. J Neurosurg 108 (4): 642-8, 2008.  [PUBMED Abstract]
   
   
4. Combs SE, Wagner J, Bischof M, et al.: Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys 70 (4): 987-92, 2008.  [PUBMED Abstract]
   
   
5. Keime-Guibert F, Chinot O, Taillandier L, et al.: Radiotherapy for glioblastoma in the elderly. N Engl J Med 356 (15): 1527-35, 2007.  [PUBMED Abstract]
   
   
6. Roa W, Brasher PM, Bauman G, et al.: Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22 (9): 1583-8, 2004.  [PUBMED Abstract]
   
   
7. Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Semin Oncol 13 (1): 38-45, 1986.  [PUBMED Abstract]
   
   
8. Rodriguez LA, Levin VA: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntingt) 1 (9): 29-36, 40-1, 1987.  [PUBMED Abstract]
   
   
9. Prados MD, Levin V: Biology and treatment of malignant glioma. Semin Oncol 27 (3 Suppl 6): 1-10, 2000.  [PUBMED Abstract]
   
   
10. Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res 6 (7): 2585-97, 2000.  [PUBMED Abstract]
    
    
11. Macdonald DR: Temozolomide for recurrent high-grade glioma. Semin Oncol 28 (4 Suppl 13): 3-12, 2001.  [PUBMED Abstract]
    
    
12. Selker RG, Shapiro WR, Burger P, et al.: The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine. Neurosurgery 51 (2): 343-55; discussion 355-7, 2002.  [PUBMED Abstract]
    
    
13. Westphal M, Hilt DC, Bortey E, et al.: A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol 5 (2): 79-88, 2003.  [PUBMED Abstract]
    
    
14. Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.  [PUBMED Abstract]
    
    
15. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al.: Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20 (5): 1375-82, 2002.  [PUBMED Abstract]
    
    
16. DeAngelis LM: Chemotherapy for brain tumors--a new beginning. N Engl J Med 352 (10): 1036-8, 2005.  [PUBMED Abstract]
    
    
17. Taphoorn MJ, Stupp R, Coens C, et al.: Health-related quality of life in patients with glioblastoma: a randomised controlled trial. Lancet Oncol 6 (12): 937-44, 2005.  [PUBMED Abstract]
    
    
18. Chamberlain MC, Glantz MJ, Chalmers L, et al.: Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 82 (1): 81-3, 2007.  [PUBMED Abstract]
    
    
19. Leibel SA, Gutin PH, Sneed PK, et al.: Interstitial irradiation for the treatment of primary and metastatic brain tumors. Cancer: Principles and Practice of Oncology Updates 3 (7): 1-11, 1989. 
    
    
20. Nelson DF, Urtasun RC, Saunders WM, et al.: Recent and current investigations of radiation therapy of malignant gliomas. Semin Oncol 13 (1): 46-55, 1986.  [PUBMED Abstract]
    
    
21. Loeffler JS, Alexander E 3rd, Shea WM, et al.: Radiosurgery as part of the initial management of patients with malignant gliomas. J Clin Oncol 10 (9): 1379-85, 1992.  [PUBMED Abstract]
    
    
22. Fontanesi J, Clark WC, Weir A, et al.: Interstitial iodine 125 and concomitant cisplatin followed by hyperfractionated external beam irradiation for malignant supratentorial glioma. Preliminary experience at the University of Tennessee, Memphis. Am J Clin Oncol 16 (5): 412-7, 1993.  [PUBMED Abstract]
    
    

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