Lung Cancer
Conditions
Keywords
stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, recurrent non-small cell lung cancer, adenocarcinoma of the lung, squamous cell lung cancer, large cell lung cancer, bronchoalveolar cell lung cancer, adenosquamous cell lung cancer
Brief summary
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Giving sorafenib together with high-dose chemotherapy and external-beam radiation therapy may kill more tumor cells. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of sorafenib when given together with high-dose carboplatin, paclitaxel, and external-beam radiation therapy in treating patients with stage III non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * To determine the median survival from randomization for patients receiving carboplatin and paclitaxel with high-dose radiation therapy (HDRT) or same regimen with sorafenib tosylate. Secondary * To determine the overall response rate, failure-free survival, and survival for patients receiving carboplatin/paclitaxel with 74 Gy HDRT or same regimen with sorafenib tosylate. * To determine the feasibility of concurrent sorafenib tosylate and chemoradiation as measured by safety (the rate of grade 3 or higher radiation related esophagitis or pulmonary toxicity or chemotherapy related grade 4 hematological or other non-hematological toxicities occurring within 60 days of the start of treatment) and compliance (the completion of the treatment regimen with no more than minor variations). * To correlate outcomes (survival, toxicity, quality of life) with biological parameters. OUTLINE: This is a multicenter study. * Phase I: * Chemoradiotherapy: Patients receive paclitaxel IV over 60 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats weekly for 7 weeks. Patients undergo concurrent high-dose external beam radiotherapy (HDRT) 5 days a week for 7.5 weeks. Cohorts of patients also receive escalating doses of oral sorafenib tosylate twice daily for 7 weeks. * Consolidation therapy: Beginning at week 11, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 weeks. Patients also receive oral sorafenib tosylate at the maximum tolerated dose (MTD) twice daily. * Maintenance: Patients receive oral sorafenib tosylate twice daily at the MTD. * Phase II: Patients are randomized to 1 of 2 treatment arms. * Arm I: * Chemoradiotherapy: Patients receive paclitaxel, carboplatin, and HDRT as in phase I. * Consolidation therapy: Patients receive paclitaxel and carboplatin as in phase I. * Arm II: * Chemoradiotherapy: Patients receive paclitaxel, carboplatin, and HDRT as in phase I. Patients also receive oral sorafenib tosylate as in phase I at the MTD. * Consolidation therapy: Patients receive paclitaxel, carboplatin, and sorafenib tosylate at the MTD as in phase I. * Maintenance: Patients receive sorafenib tosylate at the MTD as in phase I. After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 2 years.
Interventions
DRUGcarboplatin
Given IV
DRUGpaclitaxel
Given IV
DRUGsorafenib tosylate
Given orally
RADIATIONradiation therapy
Given 5 days a week for 7.5 weeks
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Histologically or cytologically documented non-small cell lung cancer (NSCLC) * Any of the following subtypes allowed: * Adenocarcinoma (including bronchoalveolar cell) * Squamous cell carcinoma * Large cell anaplastic carcinoma (including giant and clear cell carcinomas) * Poorly differentiated (not otherwise specified) NSCLC * No metastasis (patients must be M0) * Stage IIIA (T1 or T2 with N2 or T3N1-2) or stage IIIB (T4 with any N or any T with N2 or N3) disease * Measurable disease * Tumors adjacent to a vertebral body are allowed as long as all gross disease can be encompassed in the radiation boost field * The boost volume must be limited to \< 50% of the ipsilateral lung volume * Pleural effusion that is a transudate, cytologically negative, and nonbloody allowed if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy * Pleural effusions seen on the chest CT but too small to tap allowed
Exclusion criteria
* Totally resected tumors * Exudative, bloody, or cytologically malignant effusions * Known brain metastasis * Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis PATIENT CHARACTERISTICS: Inclusion criteria: * Zubrod performance status 0-1 * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL (prior to transfusions) * Total bilirubin ≤ 1.5 mg/dL * AST or ALT ≤ 3 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Glucose ≤ 2 times ULN * Creatinine ≤ 2.0 mg/dL * FEV\_1 ≥ 1,200 mL * Weight loss ≤ 10% over the past 3 months * Not pregnant or nursing * Negative pregnancy test * Women of childbearing potential and male participants who are unwilling or unable to use an acceptable method of contraception throughout the study and for 4 weeks after completion of treatment or those who are using a prohibited contraceptive method * INR \< 1.5 or a PT/PTT within normal limits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median survival | Mean 24-Months | To determine the median survival from randomization for patients receiving carboplatin / paclitaxel with high dose radiation therapy or same regimen with Sorafenib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | Mean 24-Months | To determine the overall response rate, failure-free survival and survival for patients receiving carboplatin / paclitaxel with high dose radiation therapy or same regimen with Sorafenib. |
Countries
United States
Outcome results
None listed