A randomised phase II double blind placebo controlled trial of Whole Brain RadioTherapy (WBRT) and Tarceva (OSI-774, erlotinib) in patients with advanced Non-Small Cell Lung Cancer (NSCLC) with multiple brain metastases

Phase 2

Completed

• Conditions: on-Small Cell Lung Cancer (NSCLC) with brain metastases; Cancer; Malignant neoplasm of bronchus and lung

• Registration Number: ISRCTN31916843
• Lead Sponsor: niversity College London (UK)

Brief Summary

2014 results in: https://www.ncbi.nlm.nih.gov/pubmed/25031274 [added 28/02/2019]

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-09-21
• Study Completion: 2009-12-31
• Last Update Posted: 6 April 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

1. Histologically or cytologically confirmed NSCLC. A biopsy of metastatic disease in the brain is not required for study enrolment
2. Relapsed patients with newly diagnosed multiple brain metastases
3. Diagnosis of brain metastases must be confirmed on contrast Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) scan. Subjects with post-craniotomy incomplete resection will be eligible
4. No prior cranial radiotherapy
5. >= 28 days since last chemotherapy for relapsed patients originally treated with chemotherapy
6. Clinician certain of the role of WBRT
7. Karnofsky performance status >= 70
8. The Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) class I and II
9. Symptoms attributable to brain tumour
10. Maximum of three sites (organ systems) of extracranial metastases
11. Age >18 years
12. Able to take oral medication
13. Using effective contraception if of reproductive potential (women of childbearing potential must have a negative pregnancy test performed by a healthcare professional prior to randomisation)
14. Willing and able to give informed consent
15. Carer able and willing to participate
16. Patient and carer with access to telephone and willing to respond to telephone interview

Added as of 15/09/2008:
17. Patients with brain metastases at first presentation, not suitable for first-line chemotherapy

Exclusion Criteria

1. Chemo-naïve patients with brain metastases who are considered suitable for first-line chemotherapy treatment
2. Presence of a solitary brain metastasis
3. Clinician certain that WBRT will not be of benefit
4. Clinician uncertain of the role of WBRT
5. Previous treatment with any EGFR anti-cancer therapy (e.g. Tarceva, Iressa or Cetuximab)
6. Previous treatment for brain metastases (radiosurgery, radiotherapy or chemotherapy); however, prior radiation therapy to the primary tumour and/or systemic treatment to metastatic sites of disease is acceptable
7. Pregnant or lactating women
8. Evidence of other significant laboratory finding or concurrent uncontrolled medical illness which in the opinion of the investigator would interfere with protocol treatment or results comparison or render the subject at high risk from treatment complications. For example:
8.1. Severe uncontrolled infection
8.2. Cardiovascular - unstable angina, myocardial infarction within 1 month
8.3. Gastro-intestinal - uncontrolled inflammatory bowel disease (e.g. Crohn's or ulcerative colitis)
8.4. Hepatic - serum bilirubin >= 2x upper limit of normal (ULN)
8.5. Serum transaminases >= 2 x ULN in the absence of liver metastases or >= 5 x ULN with liver metastases
8.6. Renal - acute renal failure
9. Other previous or current malignant disease likely to interfere with protocol treatment or comparisons
10. Current treatment with Cox II inhibitor

Please note that, as of 15/09/2008, the exclusion criterion MRI evidence of solitary brain metastases for resection, radiosurgery or stereotactic radiotherapy has been replaced with Presence of a solitary brain metastasis (see exclusion criterion 2)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Current primary outcome measures as of 22/02/2008:<br> To estimate the effect on neurological progression-free survival at 2 months of WBRT with concomitant Tarceva compared to WBRT alone in patients with advanced NSCLC with multiple brain metastases.<br><br> Previous primary outcome measures:<br> To estimate the effect on neurological progression-free survival at 2 months of WBRT with concomitant Tarceva compared to WBRT alone in patients with advanced NSCLC with multiple brain metastases assessed using RECIST.<br>