Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Followed by Radiation Therapy and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving carboplatin and paclitaxel albumin-stabilized nanoparticle formulation together with radiation therapy and erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving carboplatin and paclitaxel albumin-stabilized nanoparticle formulation together with radiation therapy and erlotinib works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To determine the activity of induction chemotherapy comprising carboplatin and paclitaxel albumin-stabilized nanoparticle formulation followed by concurrent thoracic radiotherapy and erlotinib hydrochloride in patients with poor-risk, unresectable stage IIIA or IIIB non-small cell lung cancer. Secondary To determine the response rate and progression-free survival of these patients. OUTLINE: Patients receive induction chemotherapy comprising paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patient with rapid disease progression outside of the chest after induction therapy are removed from study. Patients with intrathoracic disease progression within the potential radiation field may continue protocol therapy at the discretion of the Study Chair. Patients with no disease progression outside the planned radiation field (either regional or distant) proceed to concurrent erlotinib hydrochloride and radiotherapy. Beginning on day 43 (week 7), patients receive oral erlotinib hydrochloride once daily. Patients also undergo concurrent radiotherapy 5 days a week for up to 7 weeks (33 fractions) in the absence of rapid disease progression outside of the chest or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 1 year, and then every 6 months for up to 2 years

Official Title
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A Phase II Study of Induction Chemotherapy Followed by Thoracic Radiotherapy and Erlotinib in Poor-Risk Stage III Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: erlotinib hydrochloride
* Drug: paclitaxel albumin-stabilized nanoparticle formulation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following histologies: Squamous cell carcinoma Adenocarcinoma (including bronchoalveolar cell) Large cell anaplastic carcinoma (including giant and clear cell carcinomas) Must meet the following criteria: T1-3 with N2 and selected N3* T4 with N0, N1, N2 and selected N3* M0 (no M1 patients) NOTE: *Patients with contralateral mediastinal disease (i.e., N3) are eligible, provided all gross disease can be encompassed within the radiation boost field in accordance with the homogeneity criteria. Patients with ipsilateral scalene or supraclavicular disease are also eligible. Patients with contralateral hilar or supraclavicular node involvement are not eligible. Must have measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Nonmeasurable lesions include the following: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area Patients must be considered unresectable or inoperable AND be deemed candidates for combined modality therapy by a medical oncologist and a radiation oncologist Considered to be poor-risk with NCI CTC performance status (PS) 2 OR PS 0-1 and ≥ 10% weight loss within the past 3 months Patients with tumors adjacent to a vertebral body are eligible, provided all gross disease can be encompassed within the radiation boost field in accordance with the homogeneity criteria Pleural effusions meeting the following criteria allowed: Effusion is transudate, cytologically negative, and non-bloody Effusion can be seen on the chest CT scan but not on the chest x-ray AND is too small to tap Effusion appears only after a thoracotomy or other invasive thoracic procedure was attempted PATIENT CHARACTERISTICS: See Disease Characteristics Granulocytes ≥ 1,500/μL Platelet count ≥ 100,000/μL Creatinine ≤ 1.5 x upper limit of normal (ULN) AST < 2 x ULN Bilirubin ≤ ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for NSCLC At least 2 weeks since formal exploratory thoracotomy No concurrent administration of sucralfate suspension and erlotinib hydrochloride No concurrent intensity-modulated radiotherapy No concurrent hormones or other chemotherapeutic agents except steroids given for adrenal failure, hormones administered for non-disease-related conditions (e.g., insulin for diabetes), and intermittent use of dexamethasone as an antiemetic No concurrent palliative radiotherapy

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: paclitaxel + carboplatin + radiation + erlotinib<br>Patients receive paclitaxel IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patient with rapid disease progression outside of the chest after induction therapy are removed from study. Patients with intrathoracic disease progression within the potential radiation field may continue protocol therapy at the discretion of the Study Chair. Patients with no disease progression outside the planned radiation field (either regional or distant) proceed to concurrent erlotinib hydrochloride and radiotherapy. Beginning on day 43 (week 7), patients receive oral erlotinib hydrochloride once daily. Patients also undergo concurrent radiotherapy 5 days a week for up to 7 weeks (33 fractions) in the absence of rapid disease progression outside of the chest or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 1 year, and then every 6 months for up to 2 years | Drug: carboplatin<br> <br> Drug: erlotinib hydrochloride<br> <br> Drug: paclitaxel albumin-stabilized nanoparticle formulation<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 12 Months | Percentage of participants who were alive at 12 months. | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Response rate is reported as the percentage of participants who achieved each response. | Duration of study (up to 2 years) | 
| Progression-free Survival | Progression free survival (PFS) is defined as the time from registration to disease progression or death of any cause, which ever comes first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. | Duration of study (up to 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIB non-small cell lung cancer, stage IIIA non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer, squamous cell lung cancer