Radiation Therapy Followed by Bleomycin in Treating Adult Patients With Newly Diagnosed Supratentorial Glioblastoma Multiforme

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00006916
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 19
• Locations: 13
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of radiation therapy followed by bleomycin in treating adult patients who have newly diagnosed supratentorial glioblastoma multiforme.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Biological: bleomycin; Device: Ommaya reservoir; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

• Determine the median survival time of patients with newly diagnosed supratentorial glioblastoma multiforme treated with radiotherapy followed by sustained release intratumoral bleomycin.

• Determine the feasibility of this regimen in these patients.

OUTLINE: This is a multicenter study.

Within 4 weeks after surgical resection, patients receive radiotherapy daily 5 days a week for 6 weeks.

Within 2-6 weeks after completion of radiotherapy or at disease progression during radiotherapy, patients undergo surgical implantation of a modified Ommaya reservoir within the central area of the tumor. Patients then receive sustained release bleomycin intratumorally via the reservoir once a week for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study within 5 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial Of Conventional Radiation Therapy Followed By Intratumoral Bleomycin Delivered Using A Refillable, Sustained Release Device (IND# 46,592) For The Treatment Of Supratentorial Glioblastoma
• Study Start Date: Jun 1, 2001
• Actual Primary Completion Date: Dec 1, 2005
• Actual Study Completion Date: Dec 1, 2005

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Radiation therapy followed by bleomycin via Ommaya reservoir 60.0 Gy/30 fractions x 2.0 Gy. Then within 2-6 weeks after completion of radiation therapy or at the time a patient experiences disease progression during or immediately after completion of radiation therapy, if clinically feasible, a modified Ommaya reservoir is implanted with the delivery catheter in the tumor or tumor cyst/cavity. Bleomycin, 15 units per week, is then given via the Ommaya reservoir without interruption for a maximum of two years as long as there is no toxicity above grade 3 or evidence of disease progression.

Biological: bleomycin; Device: Ommaya reservoir; Radiation: radiation therapy; 60.0 Gy/30 fractions x 2.0 Gy. For the first 46 Gy/23 fractions the treatment volume should include the volume of contrast-enhancing lesion and surrounding edema on pre-operative CT/MRI scan plus a 2 centimeter margin. If no edema is present, the margin should be 2.5 cm. After 46.0 Gy, the tumor volume should include the contrast-enhancing lesion (without edema) on the pre-surgery MRI/CT scan plus a 2.5 centimeter margin.

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 18 months.]

   This study stopped accrual early with 19 subjects accrued out of 72 planned therefore no analyses were performed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial glioblastoma multiforme (with areas of necrosis) by surgical biopsy or excision within 4 weeks of study

• Tumor and/or any associated edema limited to one hemisphere and unifocal

• No gross invasion of a ventricular surface

• Tumor accessible

• No other astrocytoma

• No multifocal or recurrent malignant glioma

• No disease below the tentorium or beyond the cranial vault

PATIENT CHARACTERISTICS:

Age:

• Adult

Performance status:

• Zubrod 0-1

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Hemoglobin at least 10 g/dL (transfusion allowed)

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

• Serum glutamic-oxaloacetic transaminase (SGOT) or Serum glutamic-pyruvic transaminase (SGPT) no greater than 2 times normal

Renal:

• Blood Urea Nitrogen (BUN) no greater than 25 mg/dL

• Creatinine no greater than 1.5 mg/dL

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No hypersensitive or idiosyncratic reaction to bleomycin

• No other prior malignancies within the past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix or urinary bladder

• No other major medical illness or psychiatric impairment that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for glioblastoma multiforme

• No prior radiosensitizer for glioblastoma multiforme

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the head or neck resulting in overlapping radiotherapy fields

Surgery:

• See Disease Characteristics

• Recovered from prior surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Foundation for Cancer Research and Education	Phoenix	Arizona	United States	85013
2	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
3	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114-4199
4	South Jersey Regional Cancer Center	Millville	New Jersey	United States	08332
5	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital	Mount Holly	New Jersey	United States	08060
6	Cancer Treatment Center	Wooster	Ohio	United States	44691
7	St. John Health System	Tulsa	Oklahoma	United States	74104
8	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
9	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
10	Dixie Regional Medical Center	Saint George	Utah	United States	84770
11	LDS Hospital	Salt Lake City	Utah	United States	84143
12	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
13	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Roy A. Patchell, MD, Lucille P. Markey Cancer Center at University of Kentucky

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00006916
• Other Study ID Numbers: RTOG-BR-0013; CDR0000068343
• First Posted: Jan 27, 2003
• Last Update Posted: Oct 26, 2020
• Last Verified: Nov 1, 2015

• Keywords provided by Radiation Therapy Oncology Group: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional relevant MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Bleomycin

Study Results

Participant Flow

Arm/Group Title	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
Arm/Group Description	60.0 Gy/30 fractions x 2.0 Gy. Then within 2-6 weeks after completion of radiation therapy or at the time a patient experiences disease progression during or immediately after completion of radiation therapy, if clinically feasible, a modified Ommaya reservoir is implanted with the delivery catheter in the tumor or tumor cyst/cavity. Bleomycin, 15 units per week, is then given via the Ommaya reservoir without interruption for a maximum of two years as long as there is no toxicity above grade 3 or evidence of disease progression.
Period Title: Overall Study
STARTED	19
COMPLETED	14
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
Arm/Group Description	60.0 Gy/30 fractions x 2.0 Gy. Then within 2-6 weeks after completion of radiation therapy or at the time a patient experiences disease progression during or immediately after completion of radiation therapy, if clinically feasible, a modified Ommaya reservoir is implanted with the delivery catheter in the tumor or tumor cyst/cavity. Bleomycin, 15 units per week, is then given via the Ommaya reservoir without interruption for a maximum of two years as long as there is no toxicity above grade 3 or evidence of disease progression.
Overall Participants	19
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	7 36.8%
Male	12 63.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	This study stopped accrual early with 19 subjects accrued out of 72 planned therefore no analyses were performed.
Time Frame	From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
Arm/Group Description	60.0 Gy/30 fractions x 2.0 Gy. Then within 2-6 weeks after completion of radiation therapy or at the time a patient experiences disease progression during or immediately after completion of radiation therapy, if clinically feasible, a modified Ommaya reservoir is implanted with the delivery catheter in the tumor or tumor cyst/cavity. Bleomycin, 15 units per week, is then given via the Ommaya reservoir without interruption for a maximum of two years as long as there is no toxicity above grade 3 or evidence of disease progression.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Adverse events are reported for all subjects starting radiation therapy and/or bleomycin. Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Arm/Group Title	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
Arm/Group Description	60.0 Gy/30 fractions x 2.0 Gy. Then within 2-6 weeks after completion of radiation therapy or at the time a patient experiences disease progression during or immediately after completion of radiation therapy, if clinically feasible, a modified Ommaya reservoir is implanted with the delivery catheter in the tumor or tumor cyst/cavity. Bleomycin, 15 units per week, is then given via the Ommaya reservoir without interruption for a maximum of two years as long as there is no toxicity above grade 3 or evidence of disease progression.
All Cause Mortality
	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
	Affected / at Risk (%)	# Events
Total	5/19 (26.3%)
Blood and lymphatic system disorders
Infection (document	1/19 (5.3%)
Endocrine disorders
Endocrine-Other	1/19 (5.3%)
Investigations
Coagulation disorde	1/19 (5.3%)
Leucopenia NOS	1/19 (5.3%)
Metabolism and nutrition disorders
Hyperglycaemia NOS	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Muscle weakness NOS	1/19 (5.3%)
Nervous system disorders
Convulsions NOS	3/19 (15.8%)
Neurologic-Other	1/19 (5.3%)
Speech disorder NEC	2/19 (10.5%)
Syncope	1/19 (5.3%)
Vascular disorders
Oedema NOS	1/19 (5.3%)
Thrombosis NOS	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Radiation Therapy Followed by Bleomycin Via Ommaya Reservoir
	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)
Blood and lymphatic system disorders
Haemoglobin decreased	3/19 (15.8%)
Ear and labyrinth disorders
Earache	1/19 (5.3%)
Hearing-Other	3/19 (15.8%)
Eye disorders
Dry eye NEC	1/19 (5.3%)
Ocular-Other	4/19 (21.1%)
Vision blurred	1/19 (5.3%)
Gastrointestinal disorders
Nausea	3/19 (15.8%)
Vomiting NOS	1/19 (5.3%)
General disorders
Fatigue	11/19 (57.9%)
Pain-Other	1/19 (5.3%)
Syndromes-Other	1/19 (5.3%)
Hepatobiliary disorders
Hepatic failure	1/19 (5.3%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	3/19 (15.8%)
Ecchymosis	2/19 (10.5%)
Investigations
Alanine aminotransferase increas	1/19 (5.3%)
Aspartate aminotransferase incre	1/19 (5.3%)
Blood alkaline phosphatase NOS i	1/19 (5.3%)
Leucopenia NOS	1/19 (5.3%)
Neutropenia	1/19 (5.3%)
Platelet count decreased	2/19 (10.5%)
Metabolism and nutrition disorders
Anorexia	1/19 (5.3%)
Hyperglycaemia NOS	1/19 (5.3%)
Hypokalaemia	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Muscle weakness NOS	1/19 (5.3%)
Nervous system disorders
Amnesia NEC	1/19 (5.3%)
Convulsions NOS	5/19 (26.3%)
Depressed level of consciousness	2/19 (10.5%)
Dizziness (exc vertigo)	1/19 (5.3%)
Headache NOS	5/19 (26.3%)
Neurologic-Other	2/19 (10.5%)
Peripheral motor neuropathy	2/19 (10.5%)
Peripheral sensory neuropathy	1/19 (5.3%)
Speech disorder NEC	4/19 (21.1%)
Taste disturbance	3/19 (15.8%)
Psychiatric disorders
Anxiety NEC	1/19 (5.3%)
Confusion	1/19 (5.3%)
Depression NEC	1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	1/19 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	6/19 (31.6%)
Skin-Other	1/19 (5.3%)
Vascular disorders
Oedema NOS	3/19 (15.8%)

Limitations/Caveats

This study stopped accrual early due unmet targeted accrual goals with 19 subjects accrued out of 72 planned. No efficacy analyses were performed since the small number of patients would not have provided meaningful results.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.