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

SCH 52365 Phase II Clinical Study in Patients With Newly Diagnosed Glioblastoma Multiforme

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: 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 Names: Temodal, Temodar, SCH 052365

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events With an Incidence of Greater Than or Equal to 20%	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.	until 30 days after the completion of administration of monotherapy
Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20%	Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.	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%	Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.	until 30 days after the completion of administration of monotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression Free Survival (PFS) for 1 Year	Administration of SCH 52365 was continued until progression was observed (progression was judged by the investigator based on MRI and clinical symptoms).	1 year after the start of admininstration in the concomitant radiotherapy phase
Number of Participants With a Response (Complete Response [CR] + Partial Response [PR]) in Terms of Overall Tumor Response	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.	1 year after the start of administration in the concomitant radiotherapy phase

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2005
• Primary Completion (Actual): October 31, 2007
• Study Completion (Actual): October 31, 2007

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 22, 2008
• First Posted (Estimate): May 26, 2008

Study Record Updates

• Last Update Posted (Actual): June 7, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: P04661; JPC-05-351-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

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