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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* Pemetrexed (Alimta) 500mg/^2 administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle x 3 cycles<br>Radiation: Radiation Therapy<br>* 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.<br>|

What is the study measuring?
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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 |