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)

May 12, 2017 updated by: Merck Sharp & Dohme LLC

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

AESCA Pharma GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 8, 2005

Primary Completion (Actual)

January 16, 2008

Study Completion (Actual)

January 16, 2008

Study Registration Dates

First Submitted

December 16, 2005

First Submitted That Met QC Criteria

December 16, 2005

First Posted (Estimate)

December 19, 2005

Study Record Updates

Last Update Posted (Actual)

June 8, 2017

Last Update Submitted That Met QC Criteria

May 12, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P04071

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

http://engagezone.msd.com/ds_documentation.php

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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