Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage III Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00096226
First received: November 9, 2004
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving paclitaxel and carboplatin together with radiation therapy before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any tumor cells remaining after surgery.

PURPOSE: This phase II trial is studying how well giving paclitaxel and carboplatin together with radiation therapy works in treating patients who are undergoing surgery for stage III non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Drug: Induction Carboplatin
Drug: Induction Paclitaxel
Procedure: Resection
Drug: Consolidation Carboplatin
Radiation: Radiation Therapy
Drug: Consolidation Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial Of Neoadjuvant Therapy With Concurrent Chemotherapy And High Dose Radiotherapy Followed By Surgical Resection And Consolidative Therapy For Locally Advanced Non-Small Cell Lung Carcinoma

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Mediastinal Nodal Clearance Rate [ Time Frame: At completion of concurrent chemotherapy and radiation therapy ] [ Designated as safety issue: No ]
    If at least 12 of the first 21 evaluable patients and at least 27 of the the first 45 evaluable patients have mediastinal nodal clearance (MNC), then a conclusion of a 70% MNC rate (compared to 50%) is made using Simon's two-stage design with 90% power and 10% type I error.


Secondary Outcome Measures:
  • Rate of Complete Pathological Response After Concurrent Chemotherapy and Radiation Therapy [ Time Frame: At completion of concurrent chemotherapy and radiation therapy ] [ Designated as safety issue: No ]
  • Rate of Major Morbidities Within 30 Days of Surgery [ Time Frame: From date of surgery to 30 days following the date of surgery ] [ Designated as safety issue: Yes ]
  • Rate of Resectability After Chemotherapy [ Time Frame: At completion of concurrent chemotherapy and radiation therapy ] [ Designated as safety issue: No ]
  • Rates of R0, R1, and R2 Resections After Chemotherapy [ Time Frame: At completion of concurrent chemotherapy and radiation therapy ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: From registration to two years ] [ Designated as safety issue: No ]
  • Progression-free Survival [ Time Frame: From registration to two years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: From start of treatment to end of follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: September 2004
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
Drug: Induction Carboplatin Drug: Induction Paclitaxel Procedure: Resection Drug: Consolidation Carboplatin Radiation: Radiation Therapy Drug: Consolidation Paclitaxel

Detailed Description:

OBJECTIVES:

  • Determine the mediastinal node clearance rate in patients with stage IIIA or IIIB non-small cell lung cancer treated with neoadjuvant induction chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose radiotherapy followed by surgical resection for patients found to be resectable and consolidative chemotherapy comprising paclitaxel and carboplatin.
  • Determine the rate of complete pathological response in patients treated with this regimen.
  • Determine the feasibility of surgical resection after neoadjuvant induction chemoradiotherapy in these patients.
  • Determine disease-free and overall survival of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • Induction chemoradiotherapy: Patients undergo high-dose radiotherapy (including a total of 6 fractions of boost radiotherapy after large field radiotherapy) once daily, 5 days a week, for approximately 7 weeks. Beginning on the first day of radiotherapy, patients also receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes once weekly for 6 weeks. Patients are reassessed 4 weeks after the completion of induction chemoradiotherapy. Patients with resectable tumors undergo surgery within 2 weeks of reassessment and then receive consolidation chemotherapy no later than 10 weeks after surgery. Patients with unresectable tumors proceed directly to consolidation chemotherapy.
  • Consolidation chemotherapy: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour every 21 days for 2 courses.

Patients are followed at 6 weeks, every 3 months for 1 year, every 6 months for 2-3 years, and then annually for 4-5 years.

PROJECTED ACCRUAL: A total of 21-60 patients will be accrued for this study within 20 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer

    • Stage IIIA (T1-3, N2) or IIIB (N3)

      • No clinical or radiographic evidence of supraclavicular lymph node involvement
    • Pancoast tumors eligible
    • Mediastinal nodal disease by mediastinoscopy, thoracoscopy, Chamberlain procedure, or transbronchial needle aspirate

      • Nodes found positive by mediastinoscopy are defined as N2 disease
  • Primary tumor must be accessible for high-dose radiotherapy
  • Measurable disease
  • Potential candidate for surgery
  • No small cell lung cancer
  • No bronchoalveolar carcinoma with lobar or multilobar involvement
  • No malignant pleural effusion
  • No distant metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • At least 6 months

Hematopoietic

  • White blood cell count (WBC) ≥ 3,000/mm^3
  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
  • Albumin ≥ 3.0 g/dL

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No clinically evident superior vena cava syndrome

Pulmonary

  • Projected post-operative forced expiratory volume(FEV)_1 > 800 mL

Other

  • No known hypersensitivity to Cremophor EL
  • No unintentional weight loss ≥ 5% within the past 6 months
  • No active serious infection
  • No other serious medical condition that would preclude study participation
  • No dementia or significantly altered mental status that would preclude giving informed consent
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior systemic chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Concurrent steroids allowed as antiemetics or for prevention and amelioration of hypersensitivity reactions
  • No concurrent hormonal therapy (except megestrol for appetite stimulation, estrogen, or birth control pills)

Radiotherapy

  • No prior radiotherapy to the thorax
  • No concurrent intensity-modulated radiotherapy
  • No concurrent post-operative thoracic radiotherapy

Surgery

  • Not specified

Other

  • No other concurrent investigational therapy
  • No concurrent amifostine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096226

  Show 22 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Mohan Suntharalingam, MD University of Maryland Greenebaum Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00096226     History of Changes
Other Study ID Numbers: RTOG-0229, CDR0000389508
Study First Received: November 9, 2004
Results First Received: January 16, 2014
Last Updated: January 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 23, 2014