Concurrent Radiotherapy With Weekly Topotecan for Primary Treatment of Inoperable Localized Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Given the activity of single-agent Topotecan in NSCLC, there is both scientific rationale and a medical interest in studying this agent in combination with radiation. In addition, Topotecan administered on a weekly basis offers advantages over the daily x 5 regimen, i.e., the convenience of administration and fewer visits to the clinic.

Detailed Description
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This is a study of chemoradiation for patient with inoperable non small cell lung cancer with poor pulmonary function. These patients have usually very limited treatment options because of the compromised lung function. Chemoradiation is usually superior to radiation alone, but has not been extensively tested in this patient population. Topotecan is a drug approved for lung cancer that has synergistic activity with radiation. The study will determine what is the safest dose of topotecan to use with radiation in this patient population

Official Title
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Phase I Study of Concurrent Radiotherapy With Weekly Topotecan for Primary Treatment of Inoperable Localized Non-small Cell Lung Cancer (NSCLC) (Stage I to IIIA)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven non-small cell lung cancer Stage I to IIIA. Inoperable lung cancer because of poor respiratory lung function, or other medical reasons, as determined by the thoracic surgeon. PS < 2 Age > 18 years Life expectancy of > 12 weeks Normal hematologic, liver, and renal function No metastatic disease as determined by CT-PET scanning and bone scan. No brain metastasis by MRI No contraindication to radiotherapy Exclusion Criteria: Patients with uncontrolled CNS metastases. Active systemic infection. Serious, uncontrolled intercurrent medical or psychiatric illness. Secondary active primary malignancy. Inability to comply with requirements of the study. Any metastases outside of the mediastinum Histologically positive pleural or pericardial effusion Any chemotherapy within five years prior to enrollment on this protocol Prior radiotherapy administered to the chest Women who are pregnant or lactating FEV1 < 1 liter/minute

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Topotecan|The starting dose for the first cohort will be 2 mg/m2/week. Increment between cohorts will be by 1 mg/m2/week if no toxicity related to topotecan occurs. All members of a dose cohort must have safely completed all radiotherapy and topotecan dosing prior to beginning enrollment in the next higher dose cohort. Increments will be reduced to 0.5 mg/m2 if mild to moderate toxicity occurs (grades 1 or 2). The escalation will continue until the maximum dose of 4 mg/m2/week is reached. Therefore the minimum number of dose levels (cohorts) is 3 to reach the goal of 4 mg/m2/week, and the maximum is 5.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the establishment of the maximum tolerated dose (MTD) of topotecan given weekly with RT |  | Treatment with topotecan will last until RT is completed. Treatment will stop if there is disease progression or unacceptable toxicity |