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

This study has been terminated.
(IDMC made a recommendation to stop the trial as the target for continuing to the 2nd phase was not met.)
Sponsor:
Collaborators:
Cancer Research UK
Roche Pharma AG
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT00554775
First received: November 6, 2007
Last updated: December 9, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Metastatic Cancer
Drug: erlotinib hydrochloride
Drug: placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Neurological progression-free survival at 2 months [ Time Frame: at 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: during and for 28 days following Tarceva/placebo treatment. ] [ Designated as safety issue: Yes ]
  • Response rate [ Time Frame: from date of randomisation to radiological progression ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: completed monthly for the first 12 months and at 18 and 24 months from randomisation ] [ Designated as safety issue: No ]
  • Change in performance status [ Time Frame: from baseline ] [ Designated as safety issue: No ]
  • Steroid dosing [ Time Frame: from baseline ] [ Designated as safety issue: No ]
  • Sites of progression (cranial or extracranial) [ Time Frame: from baseline ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: January 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • tarceva
  • OSI-774
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554775

Locations
United Kingdom
Charing Cross Hospital
London, England, United Kingdom, W6 8RF
University College of London Hospitals
London, England, United Kingdom, WIT 3AA
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Salisbury District Hospital
Salisbury, England, United Kingdom, SP2 8BJ
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Glan Clwyd Hospital
Rhyl, Denbighshire, Wales, United Kingdom, LL18 5UJ
South West Wales Cancer Institute
Swansea, Wales, United Kingdom, SA2 8QA
Sponsors and Collaborators
University College, London
Cancer Research UK
Roche Pharma AG
Investigators
Study Chair: Siow M. Lee, MD, PhD, FRCP University College London Hospitals
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00554775     History of Changes
Other Study ID Numbers: CDR0000573254, CRUK-UCL-BRD-05-177, BRD/05/177, EUDRACT-2006-000113-38, CRUK-TACTIC, EU-20792, ISRCTN31916843
Study First Received: November 6, 2007
Last Updated: December 9, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by University College, London:
tumors metastatic to brain
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014