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

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Etoposide; Radiation: Radiation; Drug: Docetaxel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart Clinic
    • Evansville, Indiana, United States, 47714
      • Oncology Hematology Associates of SW Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Goshen, Indiana, United States, 46527
      • Center for Cancer Care at Goshen Health System
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Quality Cancer Center (MCGOP)
    • Indianapolis, Indiana, United States, 46256
      • Community Regional Cancer Center
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • New Albany, Indiana, United States, 47150
      • Center for Cancer Care, Inc., P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
    • Terre Haute, Indiana, United States, 47804
      • AP&S Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center
  • Texas
    • Houston, Texas, United States, 77060
      • US Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pre-Randomization; Prior to randomization patients received Cisplatin 50 mg/m^2 days 1,8,29,36 + Etoposide 50 mg/m^2 days 1-5, 29-33 + Radiation 5940 cGy (180 cGy/day). Patients with CR, PR or SD with manageable toxicity were randomized to either Docetaxel arm or Observation only arm.	Drug: Cisplatin; Cisplatin 50 mg/m2 day 1, 8, 29, 36; Other Names: Platinol; Drug: Etoposide; Etoposide 50 mg/m2, days 1-5, 29-33; Other Names: VP-16; Radiation: Radiation; Radiation 5940 cGy (180 cGy/day)
Active Comparator: Consolidation Docetaxel; Docetaxel 75 mg/m^2 q3wk X 3 cycles.	Drug: Docetaxel; docetaxel 75mg/m2 q3wk x 3 cycles; Other Names: Taxol
No Intervention: Observation Only; Patients were followed for Observation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	A comparison of overall survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median survival time and a log rank test were used to analyze the hypothesized improvement in overall survival.	Participants were measured from treatment initiation to death

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	A comparison of progression free survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median PFS time and a log rank test were used to analyze the hypothesized improvement in progression free survival. Progression is defined by RECIST as a 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion.	Participants were monitored from treatment initiation until disease progression per RECIST or death

Collaborators and Investigators

• Sponsor: Nasser Hanna, M.D.
• Collaborators: Sanofi; Walther Cancer Institute
• Investigators: Study Chair: Nasser Hanna, M.D., Hoosier Oncology Group, LLC

Publications and helpful links

General Publications

• Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R, Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P, Johnson C, Breen T, White A, Einhorn L; Hoosier Oncology Group; US Oncology. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008 Dec 10;26(35):5755-60. doi: 10.1200/JCO.2008.17.7840. Epub 2008 Nov 10.

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): March 16, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Docetaxel; Etoposide; Cisplatin
• Other Study ID Numbers: HOG LUN01-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No