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)

This study has been terminated.
(Patient target could not be reached within the planned timeframe.)
Sponsor:
Collaborator:
AESCA Pharma GmbH
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00266812
First received: December 16, 2005
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Temozolomide and radiotherapy
Procedure: Whole brain radiotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants With Progression-free Survival (6 Month) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: March 2005
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00266812     History of Changes
Other Study ID Numbers: P04071
Study First Received: December 16, 2005
Results First Received: July 29, 2009
Last Updated: April 28, 2014
Health Authority: Austria: Federal Ministry for Health and Women

Keywords provided by Merck Sharp & Dohme Corp.:
temozolomide
radiotherapy

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

ClinicalTrials.gov processed this record on October 21, 2014