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)

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00266812
• Other study ID #: P04071
• Status: Terminated
• Phase: Phase 2
• First received: December 16, 2005
• Last updated: April 29, 2015
• Start date: March 2005
• Est. completion date: January 2008

Study information

• Verified date: April 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

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).

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	AESCA Pharma GmbH

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Progression-free Survival (6 Month)	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	No