Pemetrexed and Radiation for Poor-Risk Stage III Non-Small Cell Lung Cancer

A Phase II Study of Concurrent Pemetrexed and Radiation for Poor-Risk Stage III Non-Small Cell Lung Cancer: Hoosier Oncology Group LUN08-129

Pemetrexed is approved for second line therapy in metastatic NSCLC. Given the single-agent activity of pemetrexed and the tolerability of pemetrexed in combination with radiation, this study will evaluate survival rates and toxicities in patients with poor risk stage III NSCLC.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed; Radiation: Radiation Therapy

Detailed Description

OUTLINE: This is a multi-center study.

• Pemetrexed (Alimta) 500mg/m2 administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle x 3 cycles
• Radiation will start between days -1 to 2 from day 1 of cycle 1. Day 1 radiotherapy must be a Monday, Tuesday, or Wednesday.

The planned radiation dose is 60 Gy in 2.0 Gy fractions. The entire PTV, including primary tumor and areas of known nodal disease, shall receive 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks.

Performance Status: ECOG performance status 2

Life Expectancy: Not specified

Hematopoietic:

• Platelets ≥ 100 K/mm3
• Absolute Neutrophil Count (ANC) ≥ 2.0 K/mm3

Hepatic:

• Aspartate transaminase (AST) ≤ 2.5 x ULN.
• Alanine transaminase (ALT) ≤ 2.5 x ULN.
• Total bilirubin ≤ 1.5 x ULN

Renal:

• Calculated creatinine clearance (using Cockcroft-Gault formula) ≥ 45 cc/min

Cardiovascular:

• No significant history of cardiac disease. Must not have unstable angina (anginal symptoms at rest).

Pulmonary:

• Forced expiratory volume in 1 second (FEV1) greater than 1L

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System - Kellogg Cancer Center
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Cancer Care Center of Southern Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • IN Onc/Hem Associates
    • Indianapolis, Indiana, United States, 46256
      • Community Regional Cancer Center
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • Munster, Indiana, United States, 46321
      • Monroe Medical Associates
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
    • Terre Haute, Indiana, United States, 47802
      • Providence Medical Group
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • New Jersey
    • Mt. Holly, New Jersey, United States, 08060
      • Hematology Oncology Associates S.J., P.A.
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology-Hematology Associates
    • Rockledge, Pennsylvania, United States, 19046
      • Fox Chase Cancer Center Extramural Research Program

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

Inclusion Criteria:

• Histological or cytological proof of Non Small Cell Lung Cancer (NSCLC)
• Measurable or non-measurable disease per RECIST as evaluated by imaging within 28 days prior to registration for protocol therapy
• Unresectable Stage IIIA or IIIB disease as evaluated by imaging within 28 days prior to registration for protocol therapy
• Weight loss of greater than 10% in the preceding six months prior to registration for protocol therapy.
• Serum albumin < 0.85 x institutional lower limit of normal
• Able and willing to interrupt non-steroidal anti-inflammatory agents for 2 days before (5 days for long acting agents such as piroxicam), the day of, and 2 days following administration of pemetrexed
• Lung V20 < 35% within 14 days prior to registration for protocol therapy, as planned by the radiation oncologist
• Mean lung dose < 20 Gy within 14 days prior to registration for protocol therapy, as planned by the radiation oncologist
• Written informed consent and HIPAA authorization for release of personal health information
• Age ≥ 18 years
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time of consent until at least 90 days following completion of study treatment.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.

Exclusion Criteria:

• Patients with malignant pleural effusions are not eligible. The only exception is a patient with a pleural effusion visible only on CT scan (and not visible on CXR) OR deemed too small to tap.• No CNS metastases. All patients must undergo a CT scan/MRI of the brain within 28 days prior to registration for protocol therapy to exclude brain metastasis.
• No prior chemotherapy, adjuvant therapy or radiotherapy for lung cancer.
• No metastatic disease as determined by PET scan within 28 days prior to registration for protocol therapy.
• No active clinically serious infections as judged by the treating investigator (> CTC v3, Grade 2) including known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• No other active malignancies.
• No history of collagen vascular disease (CVD).
• No significant history of cardiac disease. Must not have unstable angina (anginal symptoms at rest).
• No history of psychiatric illness/social situations that would limit compliance with study requirements.
• Females must not be breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; Pemetrexed (Alimta) 500mg/m^2 administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle x 3 cycles; Radiation will start between days -1 to 2 from day 1 of cycle 1. Day 1 radiotherapy must be a Monday, Tuesday, or Wednesday. The planned radiation dose is 60 Gy in 2.0 Gy fractions. The entire PTV, including primary tumor and areas of known nodal disease, shall receive 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks.

Drug: Pemetrexed; Pemetrexed (Alimta) 500mg/^2 administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle x 3 cycles; Radiation: Radiation Therapy; Radiation will start between days -1 to 2 from day 1 of cycle 1. Day 1 radiotherapy must be a Monday, Tuesday, or Wednesday. The planned radiation dose is 60 Gy in 2.0 Gy fractions. The entire PTV, including primary tumor and areas of known nodal disease, shall receive 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	To determine progression free survival in patients with poor risk stage III NSCLC treated with pemetrexed and concurrent definitive radiation	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Safety and Toxicity	- To determine the toxicities of pemetrexed and concurrent definitive radiation in patients with poor risk stage III NSCLC.	24 months
Overall Survival	To determine overall survival of pemetrexed and concurrent definitive radiation in patients with poor risk stage III NSCLC.	24 months

Collaborators and Investigators

• Sponsor: Hoosier Cancer Research Network
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: August 7, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 11, 2008

Study Record Updates

• Last Update Posted (Estimate): April 27, 2016
• Last Update Submitted That Met QC Criteria: March 23, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: LUN08-129