WBRT & Erlotinib in Advanced NSCLC and Brain Metastases (TACTIC)

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]

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.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: erlotinib hydrochloride; Drug: placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, W6 8RF
      • Charing Cross Hospital
    • London, England, United Kingdom, WIT 3AA
      • University College of London Hospitals
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
    • Salisbury, England, United Kingdom, SP2 8BJ
      • Salisbury District Hospital
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Wales
    • Rhyl, Denbighshire, Wales, United Kingdom, LL18 5UJ
      • Glan Clwyd Hospital
    • Swansea, Wales, United Kingdom, SA2 8QA
      • South West Wales Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: erlotinib hydrochloride; 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; PO 100 mg daily during WBRT, increasing to 150mg daily after WBRT for up to 24 months; Other Names: OSI-774; tarceva
Placebo Comparator: placebo; WBRT plus matched placebo for the same schedule and duration as erlotinib hydrochloride arm	Drug: placebo; WBRT plus matched placebo for the same schedule and duration as erlotinib hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Neurological progression-free survival at 2 months	at 2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Sites of progression (cranial or extracranial)	from baseline

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Roche Pharma AG; Cancer Research UK
• Investigators: Study Chair: Siow M. Lee, MD, PhD, FRCP, University College London Hospitals

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: November 6, 2007
• First Submitted That Met QC Criteria: November 6, 2007
• First Posted (Estimate): November 7, 2007

Study Record Updates

• Last Update Posted (Estimate): December 12, 2011
• Last Update Submitted That Met QC Criteria: December 9, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IV non-small cell lung cancer; tumors metastatic to brain
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: CDR0000573254; CRUK-UCL-BRD-05-177; BRD/05/177; EUDRACT-2006-000113-38; CRUK-TACTIC; EU-20792; ISRCTN31916843