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

• ClinicalTrials.gov Identifier: NCT00280748
• Recruitment Status: Terminated
• First Posted: January 23, 2006
• Results First Posted: June 23, 2017
• Last Update Posted: June 23, 2017
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

Tracking Information

• First Submitted Date: January 19, 2006
• First Posted Date: January 23, 2006
• Results First Submitted Date: April 3, 2017
• Results First Posted Date: June 23, 2017
• Last Update Posted Date: June 23, 2017
• Study Start Date: May 2005
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2017)

Response of Intracranial Metastases (Complete and Partial Response) [ Time Frame: 126 days ]

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.

Original Primary Outcome Measures (submitted: January 19, 2006)

• Primary Objectives
• 1. To estimate the response of intra-cranial lesions to combined whole brain radiation therapy in combination with pemetrexed

Current Secondary Outcome Measures (submitted: June 22, 2017)

• Number of Subjects Experiencing Adverse Events [ Time Frame: maximum 5 months ]
  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.
• Estimate the Overall Survival of Patients Treated With This Regimen. [ Time Frame: 4 years ]
  Patients were followed for survival from start of treatment until death from any cause (up to 4 years)
• Evaluate the Functional Status of Patients Treated With This Regimen. [ Time Frame: baseline functional status only ]
  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.
• Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification [ Time Frame: At Baseline, 30 days, and at end of treatment (maximum 5 months). ]
  A classification score defined as follows:

  1. Able to work or to perform normal activities: neurological findings minor or absent
  2. Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization
  3. Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment
  4. 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.
• Neurological Function by Mini Mental State Examination [ Time Frame: Baseline (pre-treatment), 30 days (Cycle 2 Day 1), and maximum 5 months (end of treatment). ]
  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).
• Response of Patients With Extracranial Disease Treated With Pemetrexed [ Time Frame: maximum 5 months ]
  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.

Original Secondary Outcome Measures (submitted: January 19, 2006)

• Secondary Objectives
• 1. Toxicity assessment of grade 3 or 4 toxicities
• 2. To estimate the overall survival time
• 3. To evaluate the patient's functional status over time which can be evaluated by periodic measurements using Karnofsky functional status scale
• 4. Neurological function and progression, measured by periodic evaluation of the patient's neurological function using the RTOG neurological function classification and the mini-mental status examination
• 5. Response of extra-cranial disease to pemetrexed

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer
• Official Title: A Phase II Study of Treatment of Brain Metastases From Non-Small Cell Lung Cancer With Concurrent Whole Brain Radiation Therapy and Pemetrexed

Brief Summary

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.

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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lung Cancer
• Metastatic Cancer

Intervention

• Drug: pemetrexed disodium
  500 mg/m2 once every 21 days up to 126 days
  Other Name: 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

Study Arms

Single Arm Study

Single Arm Study

Interventions:

• Drug: pemetrexed disodium
• Radiation: radiation therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 27, 2012): 10
• Original Enrollment (submitted: January 19, 2006): 30
• Actual Study Completion Date: April 2009
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00280748
• Other Study ID Numbers: LCCC 0409; CDR0000551069 ( Other Identifier: PDQ number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

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

Investigators

• Principal Investigator: Thomas E. Stinchcombe, MD; UNC Lineberger Comprehensive Cancer Center

• PRS Account: UNC Lineberger Comprehensive Cancer Center
• Verification Date: June 2017