Whole Brain Radiation With or Without Erlotinib for Brain Metastases From Non-Small Cell Lung Cancer (RadEr)

To determine if erlotinib given orally along with concurrent whole brain irradiation in lung cancer patients with brain metastases improves median overall survival and enhances local control compared to those treated with WBRT alone, without significantly increasing the risk of side effects or lowering quality of life.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Radiation: Radiation; Drug: Radiation plus erlotinib

Detailed Description

Endpoints

Primary:

• To determine if erlotinib given orally along with concurrent WBRT in lung cancer patients with brain metastases, improves median overall survival compared to those treated with WBRT alone.

Secondary:

• To confirm the safety profile of erlotinib along with concurrent WBRT, in the context of treating central nervous system malignancies.
• To evaluate if erlotinib along with concurrent WBRT increases local control rate as measured by MRI at 8 weeks, compared to WBRT alone.
• To evaluate if erlotinib along with concurrent WBRT increases time to neurologic progression of disease based on neuropsychological assessment at baseline, at 8 and 20 weeks after WBRT.
• To evaluate quality of life parameters in patients treated with WBRT alone vs concomitant erlotinib and WBRT
• To evaluate if mutation status has impact on the above mentioned parameters Trial design Open multicenter randomized phase II trial. Patients Patients > 18 years with histologically confirmed NSCLC and brain metastases verified on either CT or MRI, not eligible for neurosurgery or stereotactic radiation therapy.

Trial treatment Patients will be randomized 1:1 to either treatment arm A or B.

• Arm A: WBRT 3 Gy x10 alone.
• Arm B: WBRT 3 Gy x10 and erlotinib given concomitantly, 150 mg p.o. daily from the day before radiation, until the last day of radiation.

Number of patients 150 patients will be included, 75 in each arm

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, N-0310
    • The Norwegian Radium Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: 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 NSCLC after second-line or more chemotherapy regimens with newly diagnosed multiple brain metastases

  • Diagnosis of brain metastases confirmed by MRI (or CT if MRI is not available/possible) within the past 4 weeks
  • Symptoms attributable to brain metastases
  • Patients who have undergone craniotomy with incomplete resection are eligible
  • Clinician's opinion that whole-brain radiotherapy (WBRT) will be beneficial
  • ECOG PS 0-2
  • Age above 18 years
  • Serum bilirubin < 2 times upper limit of normal (ULN)
  • AST and ALT < 2 times ULN (< 5 times ULN if liver metastases are present)
  • Creatinine < 1.5 times ULN
  • Able to take oral medication
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other prior or concurrent malignant disease likely to interfere with study treatment or comparisons

Exclusion Criteria:

• More than 3 sites (organ systems) of extracranial metastases
• Evidence of solitary brain metastasis on MRI that can be treated with surgical resection, radiosurgery, or stereotactic radiotherapy
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiotherapy alone; Total brain irradiation, 3Gy x10	Radiation: Radiation; Whole brain radiation; Other Names: Whole brain radiation therapy
Experimental: Radiation plus erlotinib; Total brain irradiation, 3Gy x10 plus erlotinib 150 mg q d from radiation day -1 through last day of irradiation	Drug: Radiation plus erlotinib; Radiation 3Gy x10 plus erlotinib 150 mg q d, from the day before radiation start, through last day of irradiation; Other Names: Whole brain radiation therapy and tyrosin kinase inhibitor

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Odd Terje Brustugun, MD PhD, Norwegian Radium Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): December 10, 2017
• Study Completion (Actual): December 10, 2018

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: January 25, 2012
• First Posted (Estimate): January 26, 2012

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: RadEr