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

ISRCTN	ISRCTN31916843
DOI	https://doi.org/10.1186/ISRCTN31916843
EudraCT/CTIS number	2006-000113-38
ClinicalTrials.gov number	NCT00554775
Secondary identifying numbers	BRD/05/177

Submission date: 15/08/2007
Registration date: 21/09/2007
Last edited: 19/03/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-radiotherapy-with-tarceva-for-lung-cancer-that-has-spread-to-the-brain

Contact information

Dr Siow Ming Lee
Scientific

Department of Oncology
University College London Hospital (UCLH)
1st Floor Central
250 Euston Road
London
NW1 2PG
United Kingdom

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific 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
Study acronym	TACTIC
Study objectives	Tarceva has been found to have significant activity against primary brain tumours. A promising property of EGFR inhibitors is that they significantly increase the therapeutic selectivity of ionizing radiation with no increase of toxicity. It is reasonable to speculate that this property can be exploited to treat NSCLC patients with multiple cerebral metastases conventionally treated with WBRT since Tarceva can be combined with WBRT in an attempt to exploit its anti-tumour activity on brain metastases and at the same time harness its radiation-sensitising property when combined with WBRT and its beneficial systemic activity.
Ethics approval(s)	Hammersmith and Queen Charlotte's and Chelsea Research Ethics Committee, 07/03/2007, ref: 06/Q0406/141
Health condition(s) or problem(s) studied	Non-Small Cell Lung Cancer (NSCLC) with brain metastases
Intervention	Interventions: Patients are randomised 1:1 to one of two treatment arms. Each arm will receive five 4.0 Gy fractions (to isocentre), one fraction per day, over 5 days (excluding weekends) to a total dose of 20 Gy. Arm 1: Tarceva (OSI-774, erlotinib) PO (by mouth) 100 mg daily during WBRT, increasing to 150 mg daily after WBRT for up to 24 months. Arm 2: WBRT plus matched placebo for the same schedule and duration as above. Patients will be assessed 2 weekly for the first 8 weeks from Day 1 and thereafter monthly while on study drug. After stopping study drug, they will be assessed 2 monthly. The end of trial is the date the last patient completes 2 months of treatment but all patients will be followed until death.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Erlotinib
Primary outcome measure	Current primary outcome measures as of 22/02/2008: 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. Previous primary outcome measures: 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.
Secondary outcome measures	Current secondary outcome measures as of 22/02/2008: 1. Toxicity 2. Response rate. Response will be measured by CT/MRI scan and whole body scan at baseline, 2 months and at progression. 3. Quality of life assessed by EuroQol EQ-5D, completed monthly for the first 12 months and at 18 and 24 months from Day 1 4. Change in Performance Status, to investigate the time to and duration of relief of baseline symptoms, as well as tolerance of therapy 5. Steroid dosing 6. Sites of progression (cranial or extracranial) will also be recorded Previous secondary outcome measures: 1. Toxicity 2. Response rate. Response will be measured by CT/MRI scan and whole body scan at baseline, 2 months and at progression 3. Quality of life assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Questionnaires Q29 and Q30 and EuroQol EQ-5D, completed monthly for the first 12 months and at 18 and 24 months from Day 1 4. Change in Performance Status, to investigate the time to and duration of relief of baseline symptoms, as well as tolerance of therapy 5. Steroid dosing over the 2 weeks of WBRT 6. Sites of progression (cranial or extracranial) will also be recorded
Overall study start date	04/01/2008
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	144
Key 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
Key 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)
Date of first enrolment	04/01/2008
Date of final enrolment	31/12/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University College London Hospital (UCLH)

London
NW1 2PG
United Kingdom

Sponsor information

University College London (UK)
University/education

Joint University College London Hospital (UCLH) and UCL Biomedical Research Unit
Ground Floor
Rosenheim Unit
25 Grafton way
London
WC1E 5DB
England
United Kingdom

"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Charity

Cancer Research UK (UK) (ref: C1438/A6406)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration.
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	16/07/2014	28/02/2019	Yes	No

Editorial Notes

19/03/2020: EudraCT number added.
28/02/2019: Publication reference added.
26/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
15/03/2017: No publications found in PubMed, verifying study status with principal investigator.
22/02/2008: The start and end date of this trial were updated from 01/10/2007 and 31/05/2008 to 04/01/2008 and 31/12/2009, respectively.