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A Randomized Phase I/II Study Of Sorafenib In Combination With High Does Chemoradiation In Patients With Stage IIIA/B Non-small Cell Lung Cancer (NSCLC)


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Lung Cancer

Thank you

Trial Information

A Randomized Phase I/II Study Of Sorafenib In Combination With High Does Chemoradiation In Patients With Stage IIIA/B Non-small Cell Lung Cancer (NSCLC)


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.

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

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])

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Median survival

Safety Issue:

No

Principal Investigator

Hak Choy, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Simmons Cancer Center

Authority:

Unspecified

Study ID:

CDR0000571535

NCT ID:

NCT00547443

Start Date:

July 2007

Completion Date:

Related Keywords:

  • Lung Cancer
  • 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
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Arlington Cancer Center - ArlingtonArlington, Texas  76012