Cetuximab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Unresectable Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00081302
First received: April 7, 2004
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. 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 cetuximab together with combination chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with paclitaxel, carboplatin, and radiation therapy works in treating patients with unresectable stage IIIA or stage IIIB non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: cetuximab
Drug: carboplatin
Drug: paclitaxel
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Cetuximab (C225) In Combination With Chemoradiation In Patients With Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Study Start Date: March 2004
Study Completion Date: November 2013
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the feasibility of cetuximab when administered concurrently with paclitaxel, carboplatin, and radiotherapy, in terms of safety and compliance, in patients with unresectable stage IIIA or IIIB non-small cell lung cancer.

Secondary

  • Determine the response rate (complete and partial) in patients treated with this regimen.
  • Determine the overall survival (1- and 2-year survival rate and median survival) of patients treated with this regimen.
  • Determine the time to disease progression (at 1 and 2 years) in patients treated with this regimen.
  • Correlate epidermal growth factor receptor expression with the toxicity of this regimen and response, overall survival, and progression in these patients.

OUTLINE: This is a multicenter study.

  • Cetuximab loading dose (week 1): Patients receive a loading dose of cetuximab IV over 2 hours on day 1.
  • Concurrent cetuximab and chemoradiotherapy (weeks 2-8): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50-53.
  • Consolidation therapy (weeks 9-17): Patients receive cetuximab IV over 1 hour on days 57, 64, 71, 78, 85, 92, 99, 106, and 113. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 78 and 99.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days, every 3 months for 2 years, every 4 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 1 year.

  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 (NSCLC) of 1 of the following subtypes:

    • Squamous cell carcinoma
    • Adenocarcinoma (including bronchoalveolar cell)
    • Large cell anaplastic carcinoma (including giant and clear cell carcinomas)
    • Poorly differentiated/not otherwise specified NSCLC
  • Stage IIIA (T1-2, N2, M0 or T3, N1-2, M0) or IIIB (T4, any N, M0 or any T, N2-3, M0)

    • If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least 1 of the nodes must be cytologically or histologically positive
  • Unresectable disease

    • No totally resected tumors
  • Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiation boost field and the boost volume is limited to < 50% of the ipsilateral lung volume
  • Measurable disease
  • Transudate, cytologically negative, non-bloody pleural effusions allowed provided the tumor can be encompassed within a reasonable field of radiotherapy

    • Pleural effusions seen on a chest CT scan are allowed provided they are not visible on a chest x-ray and are too small to tap
  • No asymptomatic or symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL (transfusion independent)

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • SGOT (serum glutamic oxaloacetic transaminase) or SGPT (serum glutamate pyruvate transaminase) ≤ 3 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN

Renal

  • Creatinine ≤ 2.0 mg/dL

Cardiovascular

  • No significant history of cardiac disease
  • No uncontrolled hypertension
  • No unstable angina
  • No uncompensated congestive heart failure
  • No myocardial infarction within the past year
  • No cardiac ventricular arrhythmias requiring medication
  • LVEF (left ventricular ejection fraction) normal by MUGA (multi-gated acquisition) scan or echocardiogram

Pulmonary

  • No history of interstitial pneumonitis
  • No history of severe chronic obstructive pulmonary disease requiring 3 or more hospitalizations within the past year
  • FEV_1 ≥ 1,200 cc
  • No active pulmonary infection unresponsive to conventional antibiotics

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 weeks after study therapy
  • Glucose ≤ 2 times ULN
  • No more than 5% weight loss within the past 3 months
  • No known allergy to murine proteins or Cremophor EL
  • No neuropathy grade 2 or greater
  • No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ cancers

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior drugs that target the epidermal growth factor receptor pathway
  • No prior chimerized monoclonal antibody therapy
  • No other concurrent immunotherapy
  • No concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] and sargramostim [GM-CSF])

    • Concurrent epoetin alfa allowed

Chemotherapy

  • No prior systemic chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes) or steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics

Radiotherapy

  • No prior thoracic or neck radiotherapy
  • No concurrent intensity-modulated radiotherapy

Surgery

  • Recovered from prior exploratory thoracotomy
  • No prior surgical resection of the present cancer

Other

  • More than 30 days since prior participation in another clinical trial
  • No concurrent participation in another clinical trial
  • No other concurrent anticancer therapy
  • No amifostine during or for 3 months after study radiotherapy
  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: NCT00081302

Locations
United States, Texas
Arlington Cancer Center - Arlington
Arlington, Texas, United States, 76012
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: George R. Blumenschein, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Blumenschein GR, Paulus R, Curran WJ, et al.: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): A report of the 2 year and median survival (MS) for the RTOG 0324 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-7516, 2008.
Olsen CC, Paulus R, Komaki R, et al.: RTOG 0324: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients with stage IIIA/B non-small cell lung cancer (NSCLC)--Association between EGFR gene copy number and patients' outcome. [Abstract] J Clin Oncol 26 (Suppl 15): A-7607, 2008.
Blumenschein G Jr, Moughan J, Curran W, et al.: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (pts) with stage III A/B non-small cell lung cancer (NSCLC): an interim report of the RTOG 0324 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-7531, 392s, 2007.
Komaki R, Moughan J, Ang K, et al.: RTOG 0324: a phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): correlation between EGFR expression and the patients' outcome. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-101, S57-58, 2007.
Werner-Wasik M, Swann S, Curran W, et al.: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): an interim overall toxicity report of the RTOG 0324 trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-7135, 654s, 2005.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00081302     History of Changes
Other Study ID Numbers: RTOG-0324, CDR0000352163
Study First Received: April 7, 2004
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
squamous cell lung cancer
large cell lung cancer
adenocarcinoma of the lung
bronchoalveolar 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
Cetuximab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014