Temozolomide in Treating Patients With Recurrent Glioblastoma Multiforme or Other Malignant Glioma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00498927
• Collaborator: National Cancer Institute (NCI) (NIH), Weill Medical College of Cornell University (Other), Schering-Plough (Industry)
• Enrollment: 47
• Location: 1
• Arm: 1
• Duration (Months): 78
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with recurrent glioblastoma multiforme or other malignant glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: temozolomide; Genetic: protein expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Other: diagnostic laboratory biomarker analysis; Other: immunoenzyme technique	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the progression-free survival rate at 6 months in patients with recurrent glioblastoma multiforme or other malignant glioma treated with temozolomide.

Secondary

• Determine the overall survival of patients treated with this drug.

OUTLINE: Patients receive oral temozolomide once daily in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and every 2 months for 2 years for evaluation of markers of neo-angiogenesis. Samples are analyzed by protein expression, reverse-transcriptase PCR, ELISA, and western blot. (Samples are no longer being collected and tested as of 1/12/09)

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Continuous Low-Dose Temozolomide for Patients With Recurrent Malignant Glioma
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Temozolomide Following diagnosis of tumor recurrence or progression, all patients will receive of daily low dose temozolomide given at 50mg/m2/d without interruption. Brain imaging will be performed at baseline and every 2 months (standard of care). The treatment will be administered until development of toxicity, evidence of progression of disease or death.	Drug: temozolomide; Genetic: protein expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Other: diagnostic laboratory biomarker analysis; Other: immunoenzyme technique

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) Rate at 6 Months [at 6 months]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Overall Survival [2 years]

   All patients will have their tumor measurements recorded at baseline and at the time of each MRI scan. Lesions must be measured in two dimensions. The dose of gadolinium must be held constant from scan to scan. Macdonald criteria will be used for assessment of tumor response.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Pathologically diagnosed glioblastoma multiforme or other malignant glioma

• Recurrent disease

• Must have received prior temozolomide

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Granulocyte count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• SGOT ≤ 2.5 times upper limit of normal (ULN)

• Creatinine ≤ 2 times ULN

• Bilirubin ≤ 2 times ULN

• No other active malignancy except for cervical carcinoma in situ or basal cell carcinoma of the skin

• No serious medical or psychiatric illness that, in the opinion of the investigator, would preclude study treatment

• No medical condition that precludes swallowing pills

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)
• Weill Medical College of Cornell University
• Schering-Plough

Investigators

• Principal Investigator: Antonio Omuro, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Thomas Kaley, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00498927
• Other Study ID Numbers: 07-064; P30CA008748; MSKCC-07064; SPRI-PO5096
• First Posted: Jul 11, 2007
• Last Update Posted: Feb 29, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: recurrent adult brain tumor; adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult diffuse astrocytoma; adult pilocytic astrocytoma; adult subependymal giant cell astrocytoma; adult anaplastic ependymoma; adult ependymoma; adult myxopapillary ependymoma; adult subependymoma; adult anaplastic oligodendroglioma; adult oligodendroglioma; adult brain stem glioma; adult mixed glioma; adult pineal gland astrocytoma
• Additional relevant MeSH terms: Glioblastoma; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Temozolomide
Arm/Group Description	Following diagnosis of tumor recurrence or progression, all patients will receive of daily low dose temozolomide given at 50mg/m2/d without interruption. Brain imaging will be performed at baseline and every 2 months (standard of care). The treatment will be administered until development of toxicity, evidence of progression of disease or death.
Period Title: Overall Study
STARTED	47
COMPLETED	47
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Temozolomide
Arm/Group Description	Following diagnosis of tumor recurrence or progression, all patients will receive of daily low dose temozolomide given at 50mg/m2/d without interruption. Brain imaging will be performed at baseline and every 2 months (standard of care). The treatment will be administered until development of toxicity, evidence of progression of disease or death.
Overall Participants	47
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	36 76.6%
>=65 years	11 23.4%
Sex: Female, Male (Count of Participants)
Female	16 34%
Male	31 66%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Rate at 6 Months
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	at 6 months

Outcome Measure Data

Analysis Population Description

Glioblastoma patients

Arm/Group Title	Temozolomide
Arm/Group Description	Following diagnosis of tumor recurrence or progression, all patients will receive of daily low dose temozolomide given at 50mg/m2/d without interruption. Brain imaging will be performed at baseline and every 2 months (standard of care). The treatment will be administered until development of toxicity, evidence of progression of disease or death.
Measure Participants	37
Number [percentage of participants]	19 40.4%

2. Secondary Outcome

Title	Overall Survival
Description	All patients will have their tumor measurements recorded at baseline and at the time of each MRI scan. Lesions must be measured in two dimensions. The dose of gadolinium must be held constant from scan to scan. Macdonald criteria will be used for assessment of tumor response.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Glioblastoma patients

Arm/Group Title	Temozolomide
Arm/Group Description	Following diagnosis of tumor recurrence or progression, all patients will receive of daily low dose temozolomide given at 50mg/m2/d without interruption. Brain imaging will be performed at baseline and every 2 months (standard of care). The treatment will be administered until development of toxicity, evidence of progression of disease or death.
Measure Participants	37
Median (95% Confidence Interval) [months]	7

Adverse Events

Arm/Group Title	Temozolomide
Arm/Group Description	Following diagnosis of tumor recurrence or progression, all patients will receive of daily low dose temozolomide given at 50mg/m2/d without interruption. Brain imaging will be performed at baseline and every 2 months (standard of care). The treatment will be administered until development of toxicity, evidence of progression of disease or death.
All Cause Mortality
	Temozolomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Temozolomide
	Affected / at Risk (%)	# Events
Total	14/47 (29.8%)
Blood and lymphatic system disorders
AST, SGOT	1/47 (2.1%)	1
Cardiac disorders
Thrombosis/thrombus/embolism	1/47 (2.1%)	1
Gastrointestinal disorders
Dehydration	1/47 (2.1%)	1
General disorders
Confusion	3/47 (6.4%)	3
Extremity-lower (gait/walking)	2/47 (4.3%)	2
Fatigue (asthenia, lethargy, malaise)	2/47 (4.3%)	2
Mood alteration - Agitation	1/47 (2.1%)	1
Pain - Back	1/47 (2.1%)	1
Pain - Head/headache	2/47 (4.3%)	2
Seizure	2/47 (4.3%)	2
Speech impairment	1/47 (2.1%)	1
Infections and infestations
Infection, other	1/47 (2.1%)	1
Nervous system disorders
CNS cerebrovascular ischemia	1/47 (2.1%)	1
Cognitive disturbance	1/47 (2.1%)	1
Pyramidal tract dysfunction	1/47 (2.1%)	1
Neurology - Other (specify)	1/47 (2.1%)	1
Other (Not Including Serious) Adverse Events
	Temozolomide
	Affected / at Risk (%)	# Events
Total	14/47 (29.8%)
Blood and lymphatic system disorders
Leukocytes (total WBC)	6/47 (12.8%)	6
Lymphopenia	7/47 (14.9%)	7
Platelets	3/47 (6.4%)	3
General disorders
Fatigue (asthenia, lethargy, malaise)	3/47 (6.4%)	3
Metabolism and nutrition disorders
Glucose, high (hyperglycemia)	7/47 (14.9%)	7
Nervous system disorders
Neuropathy: sensory	3/47 (6.4%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.