Safety and Tolerability of Low-Dose Temozolomide During Whole Brain Radiation in Patients With Cerebral Metastases From Non-Small-Cell Lung Cancer (Study P04071)(TERMINATED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00266812
Recruitment Status : Terminated (Patient target could not be reached within the planned timeframe.)
First Posted : December 19, 2005
Results First Posted : September 4, 2009
Last Update Posted : June 8, 2017
AESCA Pharma GmbH
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a phase II, randomized, multicenter, open-label study designed to assess the safety and tolerability of concomitant chemotherapy with low-dose temozolomide during whole brain radiation and later on at 14 days on/14 days off schedule in patients with cerebral metastases from non-small cell lung cancer (NSCLC). The response to temozolomide will be evaluated by clinical follow up and Magnetic Resonance Imaging (MRI) performed every 2 months. Progression-free survival at 6 months, duration of overall survival, and quality of life will also be evaluated.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Temozolomide and radiotherapy Procedure: Whole brain radiotherapy Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study: Temozolomide (TMZ) Concomitant to Radiotherapy Followed by Sequential TMZ in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With Central Nervous System (CNS) Metastasis Versus Radiotherapy Alone
Actual Study Start Date : March 8, 2005
Actual Primary Completion Date : January 16, 2008
Actual Study Completion Date : January 16, 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Chemotherapy with temozolomide and radiotherapy Drug: Temozolomide and radiotherapy
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100 mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
Other Name: Temodal, TMZ, SCH 052365
Active Comparator: Radiotherapy alone Procedure: Whole brain radiotherapy
2 regimens are allowed: a) 20 fractions of 2 Gray each, administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.

Primary Outcome Measures :
  1. Number of Participants With Progression-free Survival (6 Month) [ Time Frame: 6 months ]
    The occurrence of progression will be compared between the study groups by Kaplan-Meier curves. Responsiveness to temozolomide will be evaluated by brain Magnetic Resonance Imanging (MRI)/Computed Tomography (CT), thorax CT, and Quality of Life (QoL) assessments. Progression-free is defined as <25% increase in tumor size on CT or MRI.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Prior histologic confirmation of non-small cell lung cancer (NSCLC).
  • Optional: NSCLC histologic confirmation of metastasis of NSCLC.
  • Presence of unidimensionally measurable disease in the brain.
  • No previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin.
  • Age: >18 years.
  • Subjects must not have systemic disease that in the opinion of the investigator is in immediate need of chemotherapy
  • Karnofsky Performance status >=70%.
  • Absolute neutrophil count (ANC) >1,500/mm^3, platelets >100,000/mm^3, hemoglobin >8 g/dL.
  • Serum creatinine and bilirubin <1.5 times upper normal limit of testing laboratory.
  • Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) <3 times upper limit of testing laboratory.
  • Palliative radiation therapy to thorax and bone or other organs (except brain) is acceptable.
  • Prior neurosurgery >2 weeks from initiating treatment with temozolomide.
  • Cortisone medication stable or decreasing within 2 weeks prior to initiating treatment with temozolomide.
  • Patient is not pregnant or nursing and is advised and willing to use an effective method of contraception.
  • Written informed consent.

Exclusion Criteria:

  • Chemotherapy or biologic therapy within four weeks prior to initiating therapy with temozolomide.
  • Prior radiation therapy for brain <4 weeks from initiating therapy with temozolomide.
  • Surgery within two weeks prior to temozolomide administration.
  • Recursive Partitioning Analysis (RPA) class III
  • Patients with a single brain metastasis amenable to radiosurgery of resection
  • Known Human Immunodeficiency Virus (HIV) disease.
  • Acute infection requiring intravenous antibiotics.
  • Any reason making compliance to the protocol improbable.

Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00266812     History of Changes
Other Study ID Numbers: P04071
First Posted: December 19, 2005    Key Record Dates
Results First Posted: September 4, 2009
Last Update Posted: June 8, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Keywords provided by Merck Sharp & Dohme Corp.:

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents