WBRT & Erlotinib in Advanced NSCLC and Brain Metastases

Lung Cancer Clinical Trial

— TACTIC  

Official title:

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 [TACTIC]

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00554775
• Other study ID #: CDR0000573254
• Secondary ID: CRUK-UCL-BRD-05-
• Status: Terminated
• Phase: Phase 2
• First received: November 6, 2007
• Last updated: December 9, 2011
• Start date: January 2008
• Est. completion date: November 2010

Study information

• Verified date: December 2011
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• Compare the effect of whole-brain radiotherapy (WBRT) and erlotinib hydrochloride vs WBRT alone on neurological progression-free survival at 2 months in patients with advanced non-small cell lung cancer and multiple brain metastases.

Secondary

• Compare the toxicity of these regimens.

• Compare the response rate in these patients.

• Compare quality of life of these patients.

• Compare change in performance status in these patients.

• Compare steroid dosing in these patients.

• Compare sites of progression (cranial or extracranial) in these patients.

OUTLINE: This is a multicenter study. Patients are stratified by presence of extracranial metastases (yes vs no), RTOG recursive partitioning analysis (RPA) score (I vs II) and treatment center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo whole-brain radiotherapy (WBRT) once daily for 5 days. Patients also receive oral erlotinib hydrochloride once daily for up to 24 months.

• Arm II: Patients undergo WBRT as in arm I. Patients also receive oral placebo once daily for up to 24 months.

Quality of life is assessed at baseline, monthly for 12 months, and then at 18 and 24 months.

After completion of study therapy, patients are followed every 1-2 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• erlotinib hydrochloride
PO 100 mg daily during WBRT, increasing to 150mg daily after WBRT for up to 24 months
• placebo
WBRT plus matched placebo for the same schedule and duration as erlotinib hydrochloride

Locations

Country	Name	City	State
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	South West Wales Cancer Institute	Swansea	Wales

Sponsors (3)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK, Roche Pharma AG

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological progression-free survival at 2 months		at 2 months	No
Secondary	Toxicity		during and for 28 days following Tarceva/placebo treatment.	Yes
Secondary	Response rate		from date of randomisation to radiological progression	No
Secondary	Quality of life		completed monthly for the first 12 months and at 18 and 24 months from randomisation	No
Secondary	Change in performance status		from baseline	No
Secondary	Steroid dosing		from baseline	No
Secondary	Sites of progression (cranial or extracranial)		from baseline	No