Temozolomide Phase II Clinical Study in Patients With Newly Diagnosed Glioblastoma Multiforme (Study P04661)(COMPLETED) - Full Text View

Purpose

The purpose of this study is to evaluate the safety of combination therapy of radiotherapy and temozolomide ("concomitant radiotherapy phase"), and then temozolomide monotherapy ("monotherapy phase"), in patients with newly diagnosed glioblastoma multiforme. Progression free survival and response rate will also be calculated.

Condition	Intervention	Phase
Glioblastoma	Radiation: Radiotherapy Drug: Temozolomide	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	SCH 52365 Phase II Clinical Study in Patients With Newly Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:

Drug Information available for: Temozolomide

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Adverse Events With an Incidence of Greater Than or Equal to 20% [ Time Frame: until 30 days after the completion of administration of monotherapy ] [ Designated as safety issue: Yes ]
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. Adverse events were classified under the system organ class using MedDRA-J Version 11.0.
Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% [ Time Frame: until 30 days after the completion of administration of monotherapy ] [ Designated as safety issue: Yes ]
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.
Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20% [ Time Frame: until 30 days after the completion of administration of monotherapy ] [ Designated as safety issue: Yes ]
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.

Secondary Outcome Measures:

Number of Participants With Progression Free Survival (PFS) for 1 Year [ Time Frame: 1 year after the start of admininstration in the concomitant radiotherapy phase ] [ Designated as safety issue: No ]
Administration of SCH 52365 was continued until progression was observed (progression was judged by the investigator based on MRI and clinical symptoms).
Number of Participants With a Response (Complete Response [CR] + Partial Response [PR]) in Terms of Overall Tumor Response [ Time Frame: 1 year after the start of administration in the concomitant radiotherapy phase ] [ Designated as safety issue: No ]
CR = measurable lesion disappeared.

PR = total sum of lesions measurable in bidimension decreased by 50% or more on whole and no secondary progression attributable to tumor was noted. No onset of new lesion.


Enrollment:	30
Study Start Date:	September 2005
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single arm It is the only arm of the study. Subjects receive a combination of radiotherapy and temozolomide, and then temozolomide monotherapy.	Radiation: Radiotherapy Radiotherapy will be administered in combination with temozolomide during the concomitant radiotherapy phase. Radiotherapy will consist of a conventionally fractioned regimen, delivering a total dose of 60 Gy in 6 weeks, in a once daily schedule of 2 Gy per fraction, for a total of 30 fractions. Radiation will be provided by a linear accelerator of x ray energy of 4 MV or higher. Other Name: Irradiation, radiation therapy Drug: Temozolomide During the concomitant radiotherapy phase (6 weeks), temozolomide will be administered in combination with radiotherapy, once daily at 75 mg/m2/day. Then, during the monotherapy phase, subjects will receive 6 cycles of temozolomide alone. Each cycle will last 28 days, and temozolomide will be administered once daily from Day 1 to Day 5 of each cycle. The dose of temozolomide in the first cycle will be 150 mg/m2/day, and may be increased to 200 mg/m2/day for Cycle 2 and subsequent cycles depending on nonhematologic toxicity observed and neutrophil and platelet count values. Capsules containing 5 mg, 20 mg, or 100 mg of temozolomide will be combined to achieve each subject's calculated dose. Other Name: Temodal, Temodar, SCH 052365

Arms

Assigned Interventions

Experimental: Single arm

It is the only arm of the study. Subjects receive a combination of radiotherapy and temozolomide, and then temozolomide monotherapy.

Radiation: Radiotherapy

Radiotherapy will be administered in combination with temozolomide during the concomitant radiotherapy phase. Radiotherapy will consist of a conventionally fractioned regimen, delivering a total dose of 60 Gy in 6 weeks, in a once daily schedule of 2 Gy per fraction, for a total of 30 fractions. Radiation will be provided by a linear accelerator of x ray energy of 4 MV or higher.

Other Name: Irradiation, radiation therapy

Drug: Temozolomide

During the concomitant radiotherapy phase (6 weeks), temozolomide will be administered in combination with radiotherapy, once daily at 75 mg/m2/day. Then, during the monotherapy phase, subjects will receive 6 cycles of temozolomide alone. Each cycle will last 28 days, and temozolomide will be administered once daily from Day 1 to Day 5 of each cycle. The dose of temozolomide in the first cycle will be 150 mg/m2/day, and may be increased to 200 mg/m2/day for Cycle 2 and subsequent cycles depending on nonhematologic toxicity observed and neutrophil and platelet count values. Capsules containing 5 mg, 20 mg, or 100 mg of temozolomide will be combined to achieve each subject's calculated dose.

Other Name: Temodal, Temodar, SCH 052365

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histopathologically confirmed newly diagnosed glioblastoma multiforme with WHO grade IV.
Histological diagnosis must be made locally after biopsy or neurosurgical tumor resection.
Four or more unstained tissue sections or a paraffin block must be provided to the Pathological Judgment Committee as tissue specimens.
Initial surgery/biopsy at diagnosis performed <=6 weeks (42 days) prior to treatment with temozolomide.
Age: >=18 and <=70 years.
ECOG performance status <=2.
Stable, non-increasing dose of corticosteroids over the 14 days prior to treatment with temozolomide.
No prior chemotherapy or radiotherapy.
Laboratory test values obtained within 14 days before initiation of administration of temozolomide must satisfy the following criteria:
- absolute neutrophil count >= 1500/mm^3;
- platelet count >= 100,000/mm^3;
- serum creatinine <=1.5 times the upper limit of laboratory normal;
- total bilirubin <=1.5 times the upper limit of laboratory normal;
- glutamic oxaloacetic transaminase or glutamic pyruvic transaminase <2.5 times the upper limit of laboratory normal;
- alkaline phosphatase < 2.5 times the upper limit of laboratory normal.
Absence of pathological conditions that interfere with taking oral drugs.
Contraception during the study period (from informed consent to the day of the last observation/examination of this study) is required in sexually active, potentially fertile patients, regardless of sex, under the supervision of the investigator or sub-investigator.
The investigator and/or subinvestigator must judge that life expectancy is 12 weeks or more.
Patients may be included regardless of sex or inpatient/outpatient.

Exclusion Criteria:

Extensively disseminated glioblastoma multiforme.
Severe disorders in the heart, liver, kidney, blood, etc.
Presence of previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and non melanoma skin cancer.
Women who are pregnant or lactating.
Women who may be pregnant or who could become pregnant and do not adopt contraception method(s).
Participation in another clinical study within 6 weeks prior to the initiation of administration of temozolomide.
Subjects who the investigator and/or subinvestigator judged inappropriate to participate in the study.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided

More Information


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT00684567 History of Changes
Other Study ID Numbers:	P04661 JPC-05-351-22
Study First Received:	May 22, 2008
Results First Received:	October 31, 2008
Last Updated:	January 19, 2015
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:


Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms	Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2016