Sorafenib and High-Dose Carboplatin, Paclitaxel, and External-Beam Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer

• Status: Withdrawn
• Trial end date: 2009-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Simmons Cancer Center; University of Texas Southwestern Medical Center
• Treatments: Albumin-Bound Paclitaxel; Carboplatin; Niacinamide; Paclitaxel; Sorafenib

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

Exclusion criteria:

• Known allergy to murine proteins or Cremophor EL

• Active pulmonary infection not responsive to conventional antibiotics

• History of severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations over the past year

• Cardiac disease including any of the following:

• Congestive heart failure > class II NYHA

• Unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months)

• Myocardial infarction within the past 6 months

• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• Patients with neuropathy > grade 1

• Evidence of malignancy in the past 2 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other in situ cancer

• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management

• Known HIV infection or chronic hepatitis B

• Active clinically serious infection > CTCAE grade 2

• Thrombolic or embolic events, such as a cerebrovascular accident including transient ischemic attacks, within the past 6 months

• Pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks

• Any other hemorrhage or bleeding event ≥ CTCAE Grade 3 within the past 4 weeks

• Serious nonhealing wound, ulcer, or bone fracture

• Evidence or history of bleeding diathesis or coagulopathy

• Known or suspected allergy to sorafenib tosylate or any agent given in the course of this trial

• Any condition that impairs patient's ability to swallow whole pills

• Any malabsorption problem

• Significant traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• Recovered from exploratory thoracotomy

• Concurrent anti-coagulation treatment with an agent such as warfarin or heparin allowed provided INR or PT/PTT requirements are met

Exclusion criteria:

• Prior systemic chemotherapy for lung cancer and/or thoracic/neck radiotherapy for any reason

• Prior surgical resection of present cancer

• Prior therapy with any molecular-targeted drugs (for lung cancer)

• Currently participating in other phase III therapeutic clinical trials and/or who have participated in other phase III therapeutic clinical trials in the previous 30 days

• Major surgery or open biopsy within the past 4 weeks

• Concurrent Hypericum perforatum (St. John's wort) or rifampin (rifampicin)

• Other concurrent anticancer drugs, including hormonal, immunotherapeutic, or chemotherapeutic agents

• Steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics allowed

• Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed

• Amifostine concurrently with radiotherapy or within 3 months of completion of radiotherapy

• Concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF])