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

Phase 2

Terminated

Conditions: Non-Small Cell Lung Cancer

Interventions: Drug: Pemetrexed
Radiation: Radiation Therapy

Registration Number: NCT00732303

Lead Sponsor: Hoosier Cancer Research Network

Brief Summary: 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.

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Radiation Therapy	* 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.
1	Pemetrexed	* 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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (18): Indiana University Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Community Regional Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Hematology Oncology Associates S.J., P.A.
🇺🇸
Mt. Holly, New Jersey, United States
Monroe Medical Associates
🇺🇸
Munster, Indiana, United States
Medical Consultants, P.C.
🇺🇸
Muncie, Indiana, United States
NorthShore University Health System - Kellogg Cancer Center
🇺🇸
Evanston, Illinois, United States
Medical & Surgical Specialists, LLC
🇺🇸
Galesburg, Illinois, United States
Northwestern University Feinberg School of Medicine
🇺🇸
Chicago, Illinois, United States
Pennsylvania Oncology-Hematology Associates
🇺🇸
Philadelphia, Pennsylvania, United States
Providence Medical Group
🇺🇸
Terre Haute, Indiana, United States
IN Onc/Hem Associates
🇺🇸
Indianapolis, Indiana, United States
Cancer Care Center of Southern Indiana
🇺🇸
Bloomington, Indiana, United States
Fort Wayne Oncology & Hematology, Inc
🇺🇸
Fort Wayne, Indiana, United States
Horizon Oncology Center
🇺🇸
Lafayette, Indiana, United States
Siteman Cancer Center
🇺🇸
St. Louis, Missouri, United States
Fox Chase Cancer Center Extramural Research Program
🇺🇸
Rockledge, Pennsylvania, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
Providence Portland Medical Center
🇺🇸
Portland, Oregon, United States