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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Etoposide
Radiation
Docetaxel
Sponsored by
Nasser Hanna, M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Medical & Surgical Specialists, LLC
  • Elkhart Clinic
  • Oncology Hematology Associates of SW Indiana
  • Fort Wayne Oncology & Hematology, Inc
  • Center for Cancer Care at Goshen Health System
  • Indiana University Cancer Center
  • Quality Cancer Center (MCGOP)
  • Community Regional Cancer Center
  • Medical Consultants, P.C.
  • Center for Cancer Care, Inc., P.C.
  • Northern Indiana Cancer Research Consortium
  • AP&S Clinic
  • Siteman Cancer Center
  • Methodist Cancer Center
  • US Oncology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Active Comparator

No Intervention

Arm Label

Pre-Randomization

Consolidation Docetaxel

Observation Only

Arm Description

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.

Docetaxel 75 mg/m^2 q3wk X 3 cycles.

Patients were followed for Observation.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
September 12, 2005
Last Updated
February 17, 2016
Sponsor
Nasser Hanna, M.D.
Collaborators
Sanofi, Walther Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00216125
Brief Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
February 2002 (undefined)
Primary Completion Date
June 2006 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nasser Hanna, M.D.
Collaborators
Sanofi, Walther Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
243 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pre-Randomization
Arm Type
Other
Arm Description
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.
Arm Title
Consolidation Docetaxel
Arm Type
Active Comparator
Arm Description
Docetaxel 75 mg/m^2 q3wk X 3 cycles.
Arm Title
Observation Only
Arm Type
No Intervention
Arm Description
Patients were followed for Observation.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol
Intervention Description
Cisplatin 50 mg/m2 day 1, 8, 29, 36
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
VP-16
Intervention Description
Etoposide 50 mg/m2, days 1-5, 29-33
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
Radiation 5940 cGy (180 cGy/day)
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxol
Intervention Description
docetaxel 75mg/m2 q3wk x 3 cycles
Primary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
Participants were measured from treatment initiation to death
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
Participants were monitored from treatment initiation until disease progression per RECIST or death

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nasser Hanna, M.D.
Organizational Affiliation
Hoosier Oncology Group, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
Medical & Surgical Specialists, LLC
City
Galesburg
State/Province
Illinois
ZIP/Postal Code
61401
Country
United States
Facility Name
Elkhart Clinic
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46515
Country
United States
Facility Name
Oncology Hematology Associates of SW Indiana
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
Facility Name
Fort Wayne Oncology & Hematology, Inc
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
Facility Name
Center for Cancer Care at Goshen Health System
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46527
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Quality Cancer Center (MCGOP)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Community Regional Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Medical Consultants, P.C.
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47303
Country
United States
Facility Name
Center for Cancer Care, Inc., P.C.
City
New Albany
State/Province
Indiana
ZIP/Postal Code
47150
Country
United States
Facility Name
Northern Indiana Cancer Research Consortium
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
AP&S Clinic
City
Terre Haute
State/Province
Indiana
ZIP/Postal Code
47804
Country
United States
Facility Name
Siteman Cancer Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Methodist Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
US Oncology
City
Houston
State/Province
Texas
ZIP/Postal Code
77060
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19001323
Citation
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.
Results Reference
result
Links:
URL
http://www.hoosieroncologygroup.org
Description
Hoosier Oncology Group Home Page

Learn more about this trial

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

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