The Effects of Continuous 28-day (28/28) Temozolomide Chemotherapy in Subjects With Recurrent Malignant Glioma Who Have Failed the Conventional 5-day (5/28) Treatment (P04601)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00392171
• Collaborator: (none)
• Enrollment: 120
• Arm: 1
• Actual Duration (Months): 39.2

Study Details

Study Description

Brief Summary

The purpose of this non-randomized, open-label, multicenter, Phase II, 2-stage design, RESCUE study is to test the hypothesis that continuous 28-day oral dosing (28/28) with dose-intense temozolomide (50 mg/m^{2) for up to 12 months may overcome resistance and be effective in the management of adult patients with malignant glioma who have failed following at least 2 cycles (2 months) of conventional 5-day (5/28) cycles of high-dose temozolomide (150-200 mg/m}2).

Condition or Disease	Intervention/Treatment	Phase
Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma	Drug: Temozolomide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Temozolomide RESCUE Study: A Phase II Trial of Continuous (28/28) Dose-intense Temozolomide (CDIT) Chemotherapy After Progression on Conventional 5/28 Day Temozolomide in Patients With Recurrent Malignant Glioma
• Actual Study Start Date: Jun 9, 2006
• Actual Primary Completion Date: Sep 15, 2009
• Actual Study Completion Date: Sep 15, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Temozolomide Temozolomide will be administered at a dose of 50 mg/m^2 for cycles of 28 days for 12 months or until progression.	Drug: Temozolomide; Subjects will receive temozolomide 50 mg/m^2 for cycles of 28 days for 12 months or until progression; Other Names: SCH 52365

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. [6 months]

   Progression-free survival as determined by Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients, greater than 18 years old.

• Surgically confirmed diagnosis of malignant glioma, specifically anaplastic glioma (anaplastic astrocytoma [AA], anaplastic oligodendroglioma [AO], anaplastic oligoastrocytoma [AOA]) or glioblastoma multiforme (GBM).

• Must have completed at least 2 cycles (2 months) of conventional 5/28 temozolomide, with radiological evidence of progression.

• GBM treated with concurrent chemoradiation with temozolomide according to the EORTC/NCIC (European Organization for Research & Treatment of Cancer/National Cancer Institute of Canada) protocol.

• Evidence of progression confirmed radiologically (CT [computed tomography] or MRI [magnetic resonance imaging]).

• Patients must be enrolled within 2 weeks of last radiological confirmation of progression, except for patients undergoing surgical resection.

• Patients undergoing surgical resection for recurrent disease must be enrolled within 2 weeks of the post-surgical scan.

• Patients with no residual disease after surgery are allowed.

• Steroids dose should have been stabilized during the last 2 weeks prior to enrollment.

• Use of medically approved contraception in fertile males and females.

• Women of childbearing potential must have a negative urine or serum pregnancy test (urinary excretion or serum level of bHCG [beta human chorionic gonadotropin]) within 24 hours of inclusion in the study.

• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

• Signed informed consent form.

Exclusion Criteria:

• GBM progression during the first 2 months of adjuvant temozolomide (5/28).

• AA progression during the first 2 months of standard temozolomide therapy (5/28).

• Chemotherapy for the malignant glioma other than temozolomide.

• More than one prior course of chemotherapy with temozolomide.

• Patient evolving from anaplastic glioma to GBM following primary therapy.

• Patient older than 70 years or who received no conventional chemoradiation regimen.

• Patient who received radiotherapy for recurrent disease.

• Patient with metastatic disease.

• Known human immunodeficiency virus (HIV) infection.

• History of non-compliance to other therapies.

• Inadequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days, inclusive, prior to study inclusion):

• Absolute neutrophil count <=1.5 ×10^9/L;

• Platelets <=100 ×10^9/L;

• Hemoglobin <90 g/L;

• Serum creatinine >=1.5 times upper limit of laboratory normal (ULN);

• Total serum bilirubin >=1.5 times ULN;

• ASAT (AST [aspartate aminotransferase]) or ALAT (ALT [alanine aminotransferase) >2.0 times ULN;

• Alkaline phosphatase of >2.5 times ULN.

• Known chronic hepatitis B or hepatitis C infection.

• Any other serious medical condition, according to the medical judgment of the physician prior to inclusion in the study.

• Any medical condition that could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction).

• Other malignancies during the previous 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal cell carcinoma or non-melanoma skin cancer.

• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule as discussed with the patient before inclusion in the study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00392171
• Other Study ID Numbers: P04601
• First Posted: Oct 25, 2006
• Last Update Posted: Jun 7, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Glioblastoma; Glioma; Astrocytoma; Oligodendroglioma; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Temozolomide
Arm/Group Description	Temozolomide will be administered at a dose of 50 mg/m^2 for cycles of 28 days for 12 months or until progression.
Period Title: Overall Study
STARTED	120
COMPLETED	15
NOT COMPLETED	105

Baseline Characteristics

Arm/Group Title	Temozolomide
Arm/Group Description	Temozolomide will be administered at a dose of 50 mg/m^2 for cycles of 28 days for 12 months or until progression.
Overall Participants	120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (11)
Sex: Female, Male (Count of Participants)
Female	44 36.7%
Male	76 63.3%
Region of Enrollment (participants) [Number]
Canada	120 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression.
Description	Progression-free survival as determined by Kaplan-Meier method.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants who received allocated intervention. The percentage of participants reported is based on the number of participants within each category (not total number of all categories combined).

Arm/Group Title	Temozolomide
Arm/Group Description	Temozolomide will be administered at a dose of 50 mg/m^2 for cycles of 28 days for 12 months or until progression.
Measure Participants	116
Anaplastic Glioma (n=28)	35.7 29.8%
Early Glioblastoma Multiforme (GBM) (n=33)	27.3 22.8%
Extended Glioblastoma Multiforme (GBM) (n=27)	7.4 6.2%
Rechallenge Glioblastoma Multiforme (GBM) (n=28)	35.7 29.8%

Adverse Events

Arm/Group Title	Temozolomide
Arm/Group Description
All Cause Mortality
	Temozolomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Temozolomide
	Affected / at Risk (%)	# Events
Total	27/120 (22.5%)
Blood and lymphatic system disorders
LEUKOPENIA	1/120 (0.8%)	1
NEUTROPENIA	1/120 (0.8%)	1
THROMBOCYTOPENIA	1/120 (0.8%)	1
Cardiac disorders
MYOCARDIAL INFARCTION	1/120 (0.8%)	1
Gastrointestinal disorders
NAUSEA	1/120 (0.8%)	1
PANCREATITIS	1/120 (0.8%)	1
VOMITING	1/120 (0.8%)	1
General disorders
ASTHENIA	1/120 (0.8%)	1
GENERAL PHYSICAL HEALTH DETERIORATION	2/120 (1.7%)	2
IRRITABILITY	1/120 (0.8%)	1
PAIN	2/120 (1.7%)	2
Infections and infestations
HERPES ZOSTER	1/120 (0.8%)	1
Injury, poisoning and procedural complications
CONTUSION	1/120 (0.8%)	2
Investigations
HEPATIC ENZYME INCREASED	1/120 (0.8%)	1
Metabolism and nutrition disorders
HYPERGLYCAEMIA	1/120 (0.8%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/120 (0.8%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM PROGRESSION	1/120 (0.8%)	1
TUMOUR HAEMORRHAGE	1/120 (0.8%)	1
Nervous system disorders
APHASIA	2/120 (1.7%)	2
ATAXIA	1/120 (0.8%)	1
BALANCE DISORDER	1/120 (0.8%)	1
CEREBRAL HAEMORRHAGE	1/120 (0.8%)	1
CONVULSION	4/120 (3.3%)	4
DEPRESSED LEVEL OF CONSCIOUSNESS	1/120 (0.8%)	1
DISTURBANCE IN ATTENTION	1/120 (0.8%)	1
DYSARTHRIA	1/120 (0.8%)	1
GRAND MAL CONVULSION	1/120 (0.8%)	1
HEADACHE	2/120 (1.7%)	2
HEMIPARESIS	1/120 (0.8%)	1
HEMIPLEGIA	1/120 (0.8%)	1
HYDROCEPHALUS	1/120 (0.8%)	1
MONOPARESIS	1/120 (0.8%)	1
POSTICTAL PARALYSIS	1/120 (0.8%)	1
SOMNOLENCE	1/120 (0.8%)	1
SPEECH DISORDER	1/120 (0.8%)	1
Psychiatric disorders
ANXIETY	1/120 (0.8%)	1
CONFUSIONAL STATE	3/120 (2.5%)	3
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM	1/120 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Temozolomide
	Affected / at Risk (%)	# Events
Total	111/120 (92.5%)
Blood and lymphatic system disorders
NEUTROPENIA	7/120 (5.8%)	7
Eye disorders
VISION BLURRED	7/120 (5.8%)	8
Gastrointestinal disorders
CONSTIPATION	15/120 (12.5%)	16
DIARRHOEA	8/120 (6.7%)	9
DYSPEPSIA	7/120 (5.8%)	7
NAUSEA	35/120 (29.2%)	40
VOMITING	24/120 (20%)	29
General disorders
ASTHENIA	8/120 (6.7%)	9
FATIGUE	48/120 (40%)	64
GAIT DISTURBANCE	13/120 (10.8%)	18
OEDEMA	7/120 (5.8%)	10
OEDEMA PERIPHERAL	9/120 (7.5%)	10
Infections and infestations
ORAL CANDIDIASIS	10/120 (8.3%)	12
Musculoskeletal and connective tissue disorders
ARTHRALGIA	8/120 (6.7%)	8
Nervous system disorders
BALANCE DISORDER	9/120 (7.5%)	11
CONVULSION	16/120 (13.3%)	22
DIZZINESS	8/120 (6.7%)	11
HEADACHE	34/120 (28.3%)	51
HEMIANOPIA	8/120 (6.7%)	9
HEMIPARESIS	22/120 (18.3%)	31
HYPOAESTHESIA	7/120 (5.8%)	8
MEMORY IMPAIRMENT	17/120 (14.2%)	28
MONOPARESIS	11/120 (9.2%)	19
SOMNOLENCE	10/120 (8.3%)	12
SPEECH DISORDER	7/120 (5.8%)	9
Psychiatric disorders
CONFUSIONAL STATE	13/120 (10.8%)	20
INSOMNIA	13/120 (10.8%)	15
Respiratory, thoracic and mediastinal disorders
COUGH	14/120 (11.7%)	16
DYSPNOEA	10/120 (8.3%)	10
Skin and subcutaneous tissue disorders
RASH	10/120 (8.3%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Study Chair agrees not to publish/present any interim results without prior Sponsor written consent. Investigators agree to provide 30 days to review prior to submission. Sponsor shall have proper representation/editorial rights/right to review/comment with regard to proprietary information. If the parties disagree concerning the appropriateness and/or confidentiality of information, Investigators agree to discuss and resolve any such issues prior to submission.