Cisplatin/Etoposide/Radiotherapy +/- Consolidation Docetaxel in Advanced Stage III Non-Small Cell Lung Cancer

Official Title: “A Phase III Trial of Cisplatin/Etoposide/Radiotherapy With or Without Consolidation Docetaxel in Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC): Hoosier Oncology Group LUN01-24”

In a previous phase II study, patients with pathological stage IIIb (without pleural effusion) NSCLC were treated with concurrent cisplatin and etoposide plus thoracic radiotherapy followed by 3 cycles of consolidation therapy with docetaxel. Docetaxel was selected based upon a survival benefit in patients with recurrent NSCLC.

This trial will evaluate the role of consolidation therapy with docetaxel in patients with unresectable stage III disease. The purpose of the trial is to evaluate survival and toxicities of the regimens employed.

OUTLINE: This is a multi-center study. - Cisplatin 50 mg/m2 d1, 8, 29, 36 - Etoposide 50 mg/m2/day d1-5, 29-33 - Radiation 5940 cGy (180 cGy/day)

Patients with CR, PR, SD Randomized to either:Docetaxel75 mg/m2 q3wk X 3 cycles

or Observation Only

Performance Status: ECOG 0 or 1

Life Expectancy: Not specified

Hematopoietic: - ANC > 1,500/mm3 - Platelet count > 100,000/mm3 - Hemoglobin > 8 g/dl. PRBC transfusions will be allowed to increase hemoglobin to >8 g/dl

Hepatic: - Serum bilirubin < institutional upper limit of normal (ULN) - AST < 2.5 X the upper limits of normal if alkaline phosphatase is < ULN, or alkaline phosphatase may be up to 4 X ULN if AST are < ULN

Renal: - Serum creatinine of < 2 mg/dl or calculated creatinine clearance > 50 cc/min

Cardiovascular: - No clinically significant history of cardiac disease, (i.e. uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the past year, or cardiac ventricular arrhythmias requiring medication).

Pulmonary: - Pre-registration FEV1 > 1 liters by spirometry within 42 days prior to study treatment.

Intervention(s) in this Clinical Trial

• Drug: Cisplatin
  • Cisplatin 50 mg/m2 day 1, 8, 29, 36
• Drug: Etoposide
  • Etoposide 50 mg/m2, days 1-5, 29-33
• Procedure: Radiotherapy
  • Radiation 5940 cGy (180 cGy/day)
• Procedure: Randomize to Further Chemotherapy or Observation
  • Patients with CR, PR or SD are randomized to either docetaxel 75mg/m2 q3wk x 3 cycles or observation only

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Cisplatin + Etoposide + Radiation. Patients with CR, PR or SD will be randomized to either Docetaxel or Observation only

Primary Measures

• To assess whether consolidation therapy with docetaxel as compared with observation following cisplatin/etoposide/radiotherapy improves overall survival for patients with unresectable stage III non-small cell lung cancer (NSCLC).
  • Time Frame: 36 months
    Safety Issue?: No

Secondary Measures

• To assess whether consolidation therapy with docetaxel as compared to observation following cisplatin/etoposide/radiotherapy improves progression free survival and to further characterize the toxicity of the addition of docetaxel in this regimen.
  • Time Frame: 36 months
    Safety Issue?: Yes

Inclusion Criteria:

• Histologic or cytologic evidence of NSCLCUnresectable Stage IIIA (N2) OR Stage IIIB
• NSCLC.
• Unresectable Stage IIIA will be defined by the following criteria:
• N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan such that in the opinion of the treating investigator, the patient is not a candidate for surgical resection
• N2 disease must be documented by biopsy, FDG-PET scan imaging, or by CT if nodes are
• > 2 cm on CT scan
• Stage IIIb patients must have N3 or T4 status. N3 status must be documented by one of the following criteria:
• Contralateral (to the primary tumor) mediastinal lymph node, supraclavicular or scalene lymph nodes proven by biopsy, FDG-PET scan imaging, or by CT if nodes are > 2 cm on CT scan.
• Patients with positive supraclavicular or scalene lymph nodes must not have disease extending up into the cervical region.
• All patients must have measurable or evaluable disease documented by CT, MRI, X-ray or physical exam within 28 days prior to study treatment.
• Negative pregnancy test
• Eligibility for Consolidation Therapy
• Following completion of induction chemoradiotherapy patients without local progression of disease or distant metastases will then be randomized to receive consolidation therapy with docetaxel or observation. Patients will be stratified and randomized based on stage IIIa vs IIIb disease at baseline, CR vs. non-CR following induction chemoradiation, and ECOG PS 0 or 1 vs. 2.
• Patients must have completed chemoradiotherapy per protocol and at least 4 weeks but no more than 8 weeks must have elapsed from the last day of induction therapy (the last day of radiation) to be eligible for randomization to consolidation with docetaxel or observation.
• Patients must have undergone re-staging tests according to the study calendar and determined to have no evidence of disease progression to be eligible for randomization to consolidation with docetaxel or observation.
• Patients must have an ANC > 1,500/mm3, platelet count > 100,000/ mm3, and hemoglobin
• > 8 g/dl obtained within 14 days prior to registration for randomization to consolidation with docetaxel or observation.
• Patients must have adequate hepatic function as defined by a serum bilirubin <
• institutional upper limit of normal (ULN) and an AST and/or ALT < 2.5 X the upper limits of normal if alkaline phosphatase is < ULN, or alkaline phosphatase may be up to 4 X ULN if transaminases are < ULN within 14 days prior to registration for randomization to consolidation with docetaxel or observation.

Exclusion Criteria:

• No prior chemotherapy or radiotherapy for lung cancer.
• No unintended weight loss > 5% body weight in the preceding 3 months prior to study treatment will not be eligible for this trial.
• No symptomatic peripheral neuropathy prior to entry onto the study. Peripheral neuropathy must be < Grade 1 to be eligible.
• No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years.
• No history of allergic reactions to drugs utilizing the vehicle polysorbate 80 (docetaxel) and polysorbate 80 + polyethylene glycol (etoposide).
• If the patient has hearing loss at pre-study, performance of an audiogram is recommended (not mandatory) to document baseline hearing status in the event of possible further hearing loss due to cisplatin administration.
• No current breastfeeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Hoosier Oncology Group Other

Overall Clinical Trial Officials and Contacts

Nasser Hanna, M.D. Study Chair Hoosier Oncology Group, LLC  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00216125

Study ID Number: HOG LUN01-24

ClinicalTrials.gov Identifier: NCT00216125

Health Authority: United States: Institutional Review Board

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