Carboplatin, Paclitaxel, and Radiation Therapy With or Without Thalidomide in Patients With Stage III Non-small Cell Lung Cancer

Phase 3

Terminated

Conditions: Lung Cancer

Interventions: Drug: carboplatin
Drug: paclitaxel
Radiation: radiation therapy
Drug: thalidomide

Registration Number: NCT00004859

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase III trial is studying carboplatin, paclitaxel, radiation therapy, and thalidomide to see how well they work compared to carboplatin, paclitaxel, and radiation therapy alone in treating patients with newly diagnosed stage III non-small cell lung cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of non-small cell lung cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without thalidomide.

Detailed Description: OBJECTIVES:

I. Compare the survival and time to progression of patients with stage IIIA or IIIB non-small cell lung cancer when treated with carboplatin, paclitaxel, and chemoradiotherapy with or without thalidomide.

II. Evaluate the toxicity of the thalidomide-containing regimen and compare response rates of the two groups.

III. Determine whether the inactivation of p16, Death-associated protein kinase (DAP-kinase), O6-methylguanine-DNA methyltransferase (MGMT) gene, or tissue-inhibitor of metalloproteinase 3 (TIMP-3) genes can be used to predict survival in these patients treated with this regimen.

IV. Determine whether the detection of a methylation biomarker in serum can be used to predict survival in these patients treated with this regimen.

OUTLINE: This is a randomized study. Patients are stratified according to disease histology (squamous vs nonsquamous), performance status (0 vs 1), disease stage (IIIA vs IIIB), and time of randomization (before addition of chemoradiotherapy vs after). Patients are randomized to one of two treatment arms.

ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours immediately followed by carboplatin IV over 15-30 minutes on days 1 and 22. Treatment continues every 22 days in the absence of unacceptable toxicity or disease progression.

ARM B: Patients receive paclitaxel and carboplatin as in arm A. Patients also receive oral thalidomide and oral low-dose aspirin daily beginning on day 1 for up to 24 months in the absence of disease progression.

Beginning between days 43-50, patients in both arms with stable or responding disease receive chemoradiotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 15-30 minutes once weekly for 6 weeks and radiotherapy (RT) 5 days a week for 6 weeks. Arm B patients continue oral thalidomide.

Patients are followed every 2 months for 2 years and then every 6 months for 3 years.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 589

Inclusion Criteria

Histologically confirmed newly diagnosed non-small cell bronchogenic carcinoma
- Squamous cell
- Adenocarcinoma
- Large cell undifferentiated
- Bronchoalveolar
- Non-small cell carcinoma not otherwise stated
Unresectable stage IIIA
- Mediastinal lymph node enlargement of at least 1 cm but less than 2 cm on computed tomography (CT) scans must have mediastinotomy or thoracoscopy to rule out resectability

Stage IIIB disease without significant pleural effusion
- Seen on CT scan only (not seen on chest x-ray) or does not reaccumulate after 1 thoracentesis and is cytologically negative
- Metastases to contralateral, mediastinal, or supraclavicular nodes allowed
Bidimensionally measurable or evaluable disease
18 and over
ECOG performance status 0-1
Adequate hematopoietic, hepatic, and renal function obtained <=4 weeks prior to registration:
- Platelet count at least 100,000/mm^3
- White Blood Cell (WBC) count at least 4,000/mm^3 OR absolute neutrophil count at least 2,000/mm^3
- Bilirubin normal
- Serum glutamic oxaloacetic transaminase (SGOT) no greater than 2.5 times upper limit of normal
- Creatinine no greater than 1.5 mg/dL OR creatinine clearance at least 60 mL/min
Fertile patients must use 2 methods of effective contraception for 4 weeks prior to, during, and for 4 weeks after study therapy
Concurrent filgrastim (G-CSF) allowed for persistent neutropenia

Exclusion Criteria

Positive pregnancy test,pregnant or nursing
Uncontrolled high blood pressure, unstable angina, congestive heart failure, or myocardial infarction within the prior year
Serious cardiac arrhythmias requiring medication
Prior radiotherapy to only area of measurable or active tumor
Less than 5 years since prior chemotherapy
Other active malignancies
Serious uncontrolled active infection
Evidence of greater than grade 1 neuropathy by history or physical examination
History of seizure disorders
Contraindication to daily low-dose (81 mg/day) aspirin

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (Paclitaxel + Carboplatin + RT)	radiation therapy	Induction chemotherapy dosing: Paclitaxel, 225 mg/m² (3 hour infusion) Day 1. Carboplatin, area under the plasma drug concentration versus time curve (AUC) =6.0, 15-30 min IV infusion immediately following paclitaxel, Day 1 Concurrent chemotherapy / radiotherapy dosing: Paclitaxel, 45 mg/m2, administered weekly during radiotherapy over one hour. Carboplatin, AUC=2, 15- 30 minutes IV infusion immediately following paclitaxel; administered weekly during radiotherapy Radiation therapy started between days 43-50 from day 1 of cycle 1. The primary tumor and areas of known nodal disease received 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks to the post chemotherapy tumor volume as seen on computed tomography (CT). The initial 50 Gy was delivered to target volume (TV). The final 10 Gy was delivered to a reduced volume targeting defined by TV
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)	radiation therapy	paclitaxel, carboplatin, and radiotherapy are same as those in Arm A. thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
Arm A (Paclitaxel + Carboplatin + RT)	carboplatin	Induction chemotherapy dosing: Paclitaxel, 225 mg/m² (3 hour infusion) Day 1. Carboplatin, area under the plasma drug concentration versus time curve (AUC) =6.0, 15-30 min IV infusion immediately following paclitaxel, Day 1 Concurrent chemotherapy / radiotherapy dosing: Paclitaxel, 45 mg/m2, administered weekly during radiotherapy over one hour. Carboplatin, AUC=2, 15- 30 minutes IV infusion immediately following paclitaxel; administered weekly during radiotherapy Radiation therapy started between days 43-50 from day 1 of cycle 1. The primary tumor and areas of known nodal disease received 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks to the post chemotherapy tumor volume as seen on computed tomography (CT). The initial 50 Gy was delivered to target volume (TV). The final 10 Gy was delivered to a reduced volume targeting defined by TV
Arm A (Paclitaxel + Carboplatin + RT)	paclitaxel	Induction chemotherapy dosing: Paclitaxel, 225 mg/m² (3 hour infusion) Day 1. Carboplatin, area under the plasma drug concentration versus time curve (AUC) =6.0, 15-30 min IV infusion immediately following paclitaxel, Day 1 Concurrent chemotherapy / radiotherapy dosing: Paclitaxel, 45 mg/m2, administered weekly during radiotherapy over one hour. Carboplatin, AUC=2, 15- 30 minutes IV infusion immediately following paclitaxel; administered weekly during radiotherapy Radiation therapy started between days 43-50 from day 1 of cycle 1. The primary tumor and areas of known nodal disease received 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks to the post chemotherapy tumor volume as seen on computed tomography (CT). The initial 50 Gy was delivered to target volume (TV). The final 10 Gy was delivered to a reduced volume targeting defined by TV
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)	carboplatin	paclitaxel, carboplatin, and radiotherapy are same as those in Arm A. thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)	paclitaxel	paclitaxel, carboplatin, and radiotherapy are same as those in Arm A. thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)	thalidomide	paclitaxel, carboplatin, and radiotherapy are same as those in Arm A. thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.

Primary Outcome Measures

Name	Time	Method
Overall Survival Time	every other month until 24 months from study entry, then every 3 months for year 3, every 4 months for year 4 and every 6 months for year 5	Survival time is defined as time from study entry to death from any cause

Secondary Outcome Measures

Name	Time	Method
Time to Disease Progression	every other month until 24 months from study entry, every 3 months for year 3, every 4 months for the 4th year and every 6 months for the 5th year	Time to disease progression is defined as the time from randomization to documented disease progression or to death without progression. Patients without documented progression or death reported were censored at the time of the last documented disease evaluation. Progression is defined, using the Response Evaluation Criteria In Solid Tumors (RECIST), as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.
Response Rate at Best Response to Treatment	every other month until 24 months from study entry, every 3 months for year 3, every 4 months for the 4th year and every 6 months for the 5th year	Proportion of patients with complete or partial response using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0. Complete response is defined as the complete disappearance of all clinically detectable malignant disease for at least 4 weeks. Partial response is defined as greater than or equal to 50% decrease in tumor size for at least 4 weeks without increase in size of any area of known malignant disease of greater than 25%, or appearance of new areas of malignant disease.

Trial Locations

Locations (233): Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸
Ft. Smith, Arkansas, United States
Memorial Medical Center Cancer Services
🇺🇸
Modesto, California, United States
Salinas Valley Memorial Hospital
🇺🇸
Salinas, California, United States
Stanford Comprehensive Cancer Center at Stanford University Medical Center
🇺🇸
Stanford, California, United States
Aurora Presbyterian Hospital
🇺🇸
Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Memorial Hospital
🇺🇸
Colorado Springs, Colorado, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸
Colorado Springs, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸
Denver, Colorado, United States
Scroll for more (223 remaining)
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸Ft. Smith, Arkansas, United States