Dexamethasone and Supportive Care With or Without Whole-Brain Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer That Has Spread to the Brain and Cannot Be Removed By Surgery

Quality of Life After Radiotherapy & Steroids. A Phase III Multi-Centre Randomised Controlled Trial to Assess Whether Optimal Supportive Care Alone (Including Dexamathasone) is As Effective as Optimal Supportive Care (Including Dexamethasone ) Plus Whole Brain Radiotherapy in the Treatment of Patients With Inoperable Brain Metastases From Non-Small Cell Lung Cancer

RATIONALE: Steroid therapy, such as dexamethasone, may reduce swelling, pain, and other symptoms of inflammation and may be effective in treating some of the problems caused by cancer and cancer treatment. Supportive care improves the quality of life of patients with a serious or life-threatening disease, and prevents or treats symptoms of cancer, side effects of treatment, and other problems related to cancer or its treatment. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether dexamethasone given together with supportive care is more effective with or without whole-brain radiation therapy in treating patients with brain metastases.

PURPOSE: This randomized phase III trial is studying dexamethasone and supportive care to see how well it works with or without whole-brain radiation therapy in improving the quality of life of patients with non-small cell lung cancer that has spread to the brain and cannot be removed by surgery.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Metastatic Cancer
• Intervention / Treatment: Radiation: radiation therapy; Drug: dexamethasone; Procedure: quality-of-life assessment

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of dexamethasone with vs without whole-brain radiotherapy in combination with optimal supportive care, in terms of patient assessed quality adjusted life years, in patients with inoperable brain metastases secondary to non-small cell lung cancer.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Assess the Karnofsky performance status of patients treated with these regimens.
• Assess the symptoms of patients treated with these regimens.
• Determine the feasibility of assessing and measuring caregiver concerns.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (experimental): Patients receive dexamethasone*. Patients receive optimal supportive care (OSC) including a prescription of a proton pump inhibitor while on dexamethasone, parallel nursing support, access to additional specialists (e.g., pain-relief service, palliative care team, medical social worker, or physiotherapist), and open access to follow-up in a specialist clinic. OSC may also include analgesics, bronchodilators, and other supportive treatment as needed.
• Arm II (control): Patients receive dexamethasone* and OSC as in arm I. Patients also undergo whole-brain radiotherapy once daily for 5 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who are receiving prednisolone at randomization need to convert to dexamethasone immediately.

All patients undergo telephone assessment, including quality of life assessment, once a week for 12 weeks and then once every 4 weeks thereafter. Consenting caregivers complete questionnaire over the telephone once a week to assess the impact of the patient's disease and treatment on the caregiver's quality of life.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: At least 1,000 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Ashington, England, United Kingdom, NE63 9JJ
      • Wansbeck General Hospital
    • Brighton, England, United Kingdom, BN2 5BE
      • Sussex Cancer Centre at Royal Sussex County Hospital
    • Bristol, England, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology Centre
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
    • Cambridge, England, United Kingdom, CB3 8RE
      • Papworth Hospital
    • Carlisle, England, United Kingdom, CA2 7HY
      • Cumberland Infirmary
    • Cheltenham, England, United Kingdom, GL53 7AN
      • Gloucestershire Oncology Centre at Cheltenham General Hospital
    • Chichester, England, United Kingdom, P019 4SE
      • Saint Richards Hospital
    • Cottingham, England, United Kingdom, HU16 5JQ
      • Castle Hill Hospital
    • Coventry, England, United Kingdom, CV2 2DX
      • Walsgrave Hospital
    • Darlington, England, United Kingdom, DL3 6HX
      • Darlington Memorial
    • Derby, England, United Kingdom, DE1 2QY
      • Derbyshire Royal Infirmary
    • Dorchester, England, United Kingdom, DT1 2JY
      • Dorset County Hospital
    • Durham, England, United Kingdom, DH1 5TW
      • University Hospital of North Durham
    • Durham, England, United Kingdom
      • Bishop Auckland Hospital
    • Exeter, England, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
    • Gateshead, England, United Kingdom, NE9 6SX
      • Queen Elizabeth Hospital
    • Grimsby, England, United Kingdom, DN33 2BA
      • Diana Princess of Wales Hospital
    • Hereford, England, United Kingdom, HR1 2ER
      • Hereford Hospitals
    • Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
      • Huddersfield Royal Infirmary
    • Hull, England, United Kingdom, HU8 9HE
      • Princess Royal Hospital at Hull and East Yorkshire NHS Trust
    • Ipswich, England, United Kingdom, IP4 5PD
      • Ipswich Hospital
    • King's Lynn, England, United Kingdom, PE30 4ET
      • Queen Elizabeth Hospital
    • Leeds, England, United Kingdom, LS16 6QB
      • Cookridge Hospital
    • Liverpool, England, United Kingdom, L9 7AL
      • Aintree University Hospital
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • London, England, United Kingdom, W2 1NY
      • St. Mary's Hospital
    • London, England, United Kingdom, E11 1NR
      • Whipps Cross Hospital
    • London, England, United Kingdom, SE1 9RT
      • Guy's Hospital
    • London, England, United Kingdom, WC1E 6DD
      • UCL Cancer Institute
    • London, England, United Kingdom, E13 85L
      • Newham University Hospital
    • London, England, United Kingdom, E9 6SR
      • Homerton University Hospital
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology
    • Middlesbrough, England, United Kingdom, TS4 3BW
      • James Cook University Hospital
    • Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
      • Northern Centre for Cancer Treatment at Newcastle General Hospital
    • North Shields, England, United Kingdom, NE29 8NH
      • North Tyneside Hospital
    • North Yorkshire, England, United Kingdom, DL6 1JG
      • Friarage Hospital
    • Northampton, England, United Kingdom, NN1 5BD
      • Northampton General Hospital
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital
    • Nuneaton, England, United Kingdom, CV10 7DJ
      • George Eliot Hospital
    • Poole Dorset, England, United Kingdom, BH15 2JB
      • Dorset Cancer Centre
    • Portsmouth Hants, England, United Kingdom, PO3 6AD
      • Portsmouth Oncology Centre at Saint Mary's Hospital
    • Prescot Merseyside, England, United Kingdom, L35 5DR
      • Whiston Hospital
    • Reading, England, United Kingdom, RG1 5AN
      • Berkshire Cancer Centre at Royal Berkshire Hospital
    • Redditch, Worcestershire, England, United Kingdom, B98 7UB
      • Alexandra Healthcare NHS
    • South Shields, England, United Kingdom, NE34 0PL
      • South Tyneside District Hospital
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
    • Southport, England, United Kingdom, PR8 6PN
      • Southport and Formby District General Hospital
    • Stockton-On-Tees, England, United Kingdom, TS19 8PE
      • University Hospital of North Tees
    • Taunton, England, United Kingdom, TA1 5DA
      • Taunton and Somerset Hospital
    • Torquay, England, United Kingdom, TQ2 7AA
      • Torbay Hospital
    • Truro, England, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
    • Walsall, England, United Kingdom, WS2 9PS
      • Walsall Manor Hospital
    • Warwick, Warwickshire, England, United Kingdom, CV34 5BJ
      • South Warwickshire Hospital
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital
    • Worcester, England, United Kingdom, WR5 1DD
      • Worcester Royal Hospital
    • York, England, United Kingdom, Y031 8HE
      • Cancer Care Centre at York Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Centre for Cancer Research and Cell Biology at Queen's University Belfast
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Ninewells Hospital
    • East Kilbride, Scotland, United Kingdom, G75 8RG
      • Hairmyres Hospital
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Edinburgh Cancer Centre at Western General Hospital
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Beatson West of Scotland Cancer Centre
    • Inverness, Scotland, United Kingdom, 1V2 3UJ
      • Raigmore Hospital
    • Kilmarnock, Scotland, United Kingdom, KA2 OBE
      • Crosshouse Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 2TL
      • Velindre Cancer Center at Velindre Hospital
    • Llandough, Wales, United Kingdom, CF64 2XX
      • LLandough Hospital
    • Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
      • Glan Clwyd Hospital

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 primary non-small cell lung cancer

• Must have brain metastases confirmed by CT scan or MRI

  • Unresectable disease OR surgery is deemed inappropriate

• The benefit or lack of benefit of whole-brain radiotherapy (WBRT) cannot be clearly defined

  • Any known certainty of the benefit or lack of benefit of WBRT is not allowed

PATIENT CHARACTERISTICS:

• No prior or concurrent uncontrolled illness that could preclude study treatment or comparisons
• Must be able to respond to weekly telephone assessment questions

PRIOR CONCURRENT THERAPY:

• More than 1 week since prior epidermal growth factor receptor inhibitors
• More than 1 month since prior chemotherapy
• More than 1 month since prior surgery for brain metastases
• No prior radiotherapy to the brain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Patient-assessed quality adjusted life years

Secondary Outcome Measures

Outcome Measure
Overall survival
Karnofsky performance status
Patient symptoms
Assessment and measurement of caregiver concerns

Collaborators and Investigators

• Sponsor: Medical Research Council
• Investigators: Study Chair: Paula Mulvenna, Northern Centre for Cancer Treatment at Newcastle General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: November 21, 2006
• First Submitted That Met QC Criteria: November 21, 2006
• First Posted (Estimate): November 23, 2006

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: January 1, 2007

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: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: CDR0000517194; MRC-LU24-QUARTZ; EU-20653; ISRCTN3826061; TROG 07.02