Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer (NRR)

A Phase II Study of Treatment of Brain Metastases From Non-Small Cell Lung Cancer With Concurrent Whole Brain Radiation Therapy and Pemetrexed

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with pemetrexed may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving whole-brain radiation therapy together with pemetrexed works in treating patients with brain metastases from non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: pemetrexed disodium; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Estimate the response in patients with intracranial brain metastases from non-small cell lung cancer treated with whole-brain radiotherapy and pemetrexed disodium.

Secondary

• Determine the toxicity of this regimen in these patients.
• Estimate the overall survival of patients treated with this regimen.
• Evaluate the functional status of patients treated with this regimen.
• Assess neurological function and progression in patients treated with this regimen.
• Determine the response of patients with extracranial disease treated with pemetrexed disodium.

OUTLINE: Patients undergo whole-brain radiotherapy 5 days a week for 3 weeks beginning on day 1. Patients also receive pemetrexed disodium IV on day 1, 2, or 3 and day 28 of course 1, and on day 1 of each subsequent course. Treatment with pemetrexed disodium repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 2 months for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Burlington, North Carolina, United States, 27216
      • Alamance Oncology/Hematology Associates, LLP
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

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 non-small cell lung cancer (NSCLC)
• Must have evidence of brain metastases by MRI or CT scan

PRIOR CONCURRENT THERAPY:

• Recovered from prior oncologic or major surgery
• Prior resection of all brain metastases or only site of brain metastases allowed provided there is radiologically evaluable intracranial metastases
• No prior cranial irradiation, including stereotactic radiosurgery
• More than 30 days since prior non-approved or investigational drug

• No other concurrent chemotherapy, immunotherapy, hormonal therapy, radiotherapy, surgery, or experimental medications

  • No single brain metastases or oligometastatic disease amenable to surgical resection or radiosurgery
• Relapsed NSCLC with brain metastases allowed
• Not a candidate for double-agent or platinum-based chemotherapy
• No leptomeningeal metastases
• No clinically relevant (defined by physical exam) pleural effusions or ascites that cannot be controlled with drainage or other procedures

Inclusion Criteria:

• Karnofsky performance status 70-100% OR ≥ 70 years of age
• Life expectancy > 3 months
• Absolute neutrophil count (ANC) > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin ≥ 8 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Creatinine clearance ≥ 45 mL/min
• Able to take vitamins, folic acid, and corticosteroids

Exclusion Criteria:

• Contraindication or intolerance to corticosteroid therapy
• Other malignancies within the past 5 years and disease-free OR prognosis is best defined by the NSCLC in the opinion of the attending physician
• Pregnant or nursing
• Positive pregnancy test
• Fertile patients must use effective contraception
• HIV positive
• Severe hypersensitivity to pemetrexed disodium
• Unable to discontinue NSAIDs for ≥ 5 days
• History of underlying dementia, Parkinson's disease, or Alzheimer's disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single Arm Study	Drug: pemetrexed disodium; 500 mg/m2 once every 21 days up to 126 days; Other Names: Alimta; Radiation: radiation therapy; Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response of Intracranial Metastases (Complete and Partial Response)	Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	126 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Experiencing Adverse Events	Toxicities was assessed using Common Terminology Criteria for Adverse Events (CTCAE) grading scale. Only toxicities with attribution to chemotherapy of "definite" or "probable" are considered, as determined by treating physician.	maximum 5 months
Estimate the Overall Survival of Patients Treated With This Regimen.	Patients were followed for survival from start of treatment until death from any cause (up to 4 years)	4 years
Evaluate the Functional Status of Patients Treated With This Regimen.	Functional status evaluated using the Karnofsky functional status scale. The Karnofsky Performance Scale (KPS) Index allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.	baseline functional status only
Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification	A classification score defined as follows: Able to work or to perform normal activities: neurological findings minor or absent; Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization; Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment; Unable to perform even minimal normal activities. Requiring hospitalization and constant nursing care and feeding. Patients unable to communicate or in coma.A higher score indicates worse function.	At Baseline, 30 days, and at end of treatment (maximum 5 months).
Neurological Function by Mini Mental State Examination	The Mini Mental State Examination is a 30-point questionnaire that is used to measure cognitive impairment. Score totals range from normal cognition (24-30 points), mild impairment (19-23 points), moderate impairment (10-18 points), to severe impairment (≤9 points).	Baseline (pre-treatment), 30 days (Cycle 2 Day 1), and maximum 5 months (end of treatment).
Response of Patients With Extracranial Disease Treated With Pemetrexed	Response was measured by Response Evaluation Criteria In Solid Tumors RECIST criteria v1.0. Complete Response (CR) - Disappearance of all lesions Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD) - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing nontarget lesions.	maximum 5 months

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 19, 2006
• First Submitted That Met QC Criteria: January 19, 2006
• First Posted (Estimate): January 23, 2006

Study Record Updates

• Last Update Posted (Actual): June 23, 2017
• Last Update Submitted That Met QC Criteria: June 22, 2017
• Last Verified: June 1, 2017

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; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: LCCC 0409; CDR0000551069 (Other Identifier: PDQ number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO