WBRT & Erlotinib in Advanced NSCLC and Brain Metastases

NCT00554775 | Terminated Phase 2 DMC

• 7 other identifiers: CDR0000573254CRUK-UCL-BRD-05-177BRD/05/177EUDRACT-2006-000113-38CRUK-TACTICEU-20792ISRCTN31916843
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 7

Brief Summary

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib may also make tumor cells more sensitive to radiation therapy. It is not yet known whether giving whole-brain radiation therapy together with erlotinib is more effective than whole-brain radiation therapy alone in treating patients with non-small cell lung cancer and brain metastases. PURPOSE: This randomized phase II trial is studying whole-brain radiation therapy and erlotinib to see how well they work compared with whole-brain radiation therapy alone in treating patients with advanced non-small cell lung cancer and brain metastases.

Conditions

Lung Cancer; Metastatic Cancer

Keywords

tumors metastatic to brain; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Neurological progression-free survival at 2 months

  at 2 months

Secondary Outcomes (6)

• Toxicity

  during and for 28 days following Tarceva/placebo treatment.

• Response rate

  from date of randomisation to radiological progression

• Quality of life

  completed monthly for the first 12 months and at 18 and 24 months from randomisation

• Change in performance status

  from baseline

• Steroid dosing

  from baseline

Study Arms (2)

erlotinib hydrochloride

EXPERIMENTAL

WBRT plus Tarceva (OSI-774, erlotinib) PO 100 mg daily during WBRT, increasing to 150mg daily after WBRT for up to 24 months

Drug: erlotinib hydrochloride

placebo

PLACEBO COMPARATOR

WBRT plus matched placebo for the same schedule and duration as erlotinib hydrochloride arm

Drug: placebo

Interventions

erlotinib hydrochloride DRUG

PO 100 mg daily during WBRT, increasing to 150mg daily after WBRT for up to 24 months

Also known as: tarceva, OSI-774

erlotinib hydrochloride

placebo DRUG

WBRT plus matched placebo for the same schedule and duration as erlotinib hydrochloride

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC) meeting 1 of the following criteria: * Newly diagnosed multiple brain metastases not suitable for first-line chemotherapy * Relapsed NSCLC with newly diagnosed multiple brain metastases * Relapsed after second-line chemotherapy with newly diagnosed multiple brain metastases NOTE: \*Biopsy of brain metastases is not required * Diagnosis of brain metastases must be confirmed by contrast CT scan or MRI within the past 4 weeks * Symptoms attributable to brain metastases * Patients who have undergone craniotomy with incomplete resection are eligible * Clinician certain that whole-brain radiotherapy (WBRT) will be beneficial * No evidence of solitary brain metastasis on MRI that can be treated with surgical resection, radiosurgery, or stereotactic radiotherapy * No more than 3 sites (organ systems) of extracranial metastases * No liver metastases PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * RTOG recursive partitioning analysis (RPA) class I or II * Serum bilirubin \< 2 times upper limit of normal (ULN) * AST and ALT \< 2 times ULN (\< 5 times ULN if liver metastases are present) * Creatinine \< 5 times ULN * Able to take oral medication * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Caretaker able and willing to participate in the study * Patient and caretaker have access to a telephone and willing to respond to telephone interview * No other prior or concurrent malignant disease likely to interfere with study treatment or comparisons * No evidence of other significant laboratory finding or concurrent uncontrolled medical illness, that in the opinion of the investigator, would interfere with study treatment or results comparison or render the patient at high risk for treatment complications including, but not limited to, any of the following: * Severe uncontrolled infection * Unstable angina * Myocardial infarction within the past month * Uncontrolled inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) * Acute renal failure PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 28 days since prior chemotherapy (for relapsed patients originally treated with chemotherapy) * No prior cranial radiotherapy * No prior anti-cancer EGFR therapy (e.g., erlotinib, gefitinib, or cetuximab) * No prior treatment for brain metastases (e.g., radiosurgery, radiotherapy, or chemotherapy) * Prior radiotherapy to the primary tumor and/or systemic treatment to metastatic sites of disease allowed * No concurrent cyclooxygenase-2 (COX-2) inhibitors

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator
• Roche Pharma AG: collaborator

Study Sites (7)

Charing Cross Hospital

London, England, W6 8RF, United Kingdom

Location

University College of London Hospitals

London, England, WIT 3AA, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Salisbury District Hospital

Salisbury, England, SP2 8BJ, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, LL18 5UJ, United Kingdom

Location

South West Wales Cancer Institute

Swansea, Wales, SA2 8QA, United Kingdom

Location

MeSH Terms

Conditions

Lung Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Siow M. Lee, MD, PhD, FRCP

  University College London Hospitals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2007
• First Posted: November 7, 2007
• Study Start: January 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: December 12, 2011

Record last verified: 2011-12

Locations

GB (7)