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

Phase 1
Withdrawn
Conditions
Lung Cancer
Interventions
Registration Number
NCT00547443
Lead Sponsor
University of Texas Southwestern Medical Center
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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm Iradiation therapyPatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose external beam radiotherapy (HDRT) as in phase I. Patients also receive consolidation therapy comprising paclitaxel and carboplatin as in phase I.
Arm IIradiation therapyPatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and HDRT as in phase I. Patients also receive consolidation therapy comprising paclitaxel, carboplatin, and sorafenib tosylate at the MTD as in phase I, as well as maintenance therapy comprising sorafenib tosylate at the MTD as in phase I.
Arm IIsorafenib tosylatePatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and HDRT as in phase I. Patients also receive consolidation therapy comprising paclitaxel, carboplatin, and sorafenib tosylate at the MTD as in phase I, as well as maintenance therapy comprising sorafenib tosylate at the MTD as in phase I.
Arm IcarboplatinPatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose external beam radiotherapy (HDRT) as in phase I. Patients also receive consolidation therapy comprising paclitaxel and carboplatin as in phase I.
Arm IpaclitaxelPatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose external beam radiotherapy (HDRT) as in phase I. Patients also receive consolidation therapy comprising paclitaxel and carboplatin as in phase I.
Arm IIpaclitaxelPatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and HDRT as in phase I. Patients also receive consolidation therapy comprising paclitaxel, carboplatin, and sorafenib tosylate at the MTD as in phase I, as well as maintenance therapy comprising sorafenib tosylate at the MTD as in phase I.
Arm IIcarboplatinPatients receive chemoradiotherapy comprising paclitaxel, carboplatin, and HDRT as in phase I. Patients also receive consolidation therapy comprising paclitaxel, carboplatin, and sorafenib tosylate at the MTD as in phase I, as well as maintenance therapy comprising sorafenib tosylate at the MTD as in phase I.
Primary Outcome Measures
NameTimeMethod
Median survivalMean 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 Outcome Measures
NameTimeMethod
Progression-free survivalMean 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.

Trial Locations

Locations (2)

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

🇺🇸

Dallas, Texas, United States

Arlington Cancer Center - Arlington

🇺🇸

Arlington, Texas, United States

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