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Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

Primary Purpose

Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
cisplatin
docetaxel
etoposide
gefitinib
radiation therapy
placebo
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Lung

Eligibility Criteria

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

Inclusion Criteria: Either histologic or cytologic proof of a newly diagnosed single, primary bronchogenic non-small cell lung cancer is required (adenocarcinoma, non-lobar and non-diffuse bronchioloalveolar cell carcinoma, large cell carcinoma, or squamous cell carcinoma); a biopsy with histology is preferred, but cytology is allowed; histology or cytology from involved mediastinal or supraclavicular lymph nodes alone will be allowed if a separate distal primary lesion is clearly evident on radiographs (i.e., a second biopsy will not be required) Patients with brain metastases are ineligible; all patients must have a pretreatment CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration Patients with two or more parenchymal lesions on same or opposite sides of the lung are ineligible Patients must have unresectable Stage IIIA (N2) or Stage IIIB disease and also satisfy the following criteria: Unresectable Stage IIIA (N2) patients must satisfy the criteria: N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or X-ray, such that, in the opinion of the treating investigator, the patient is not a candidate for induction chemotherapy or chemoradiotherapy followed by surgical resection If Stage IIIA (N2), the N2 status must be documented by any one of the following methods: Histologic or cytologic proof of N2 disease by exploratory thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy, Chamberlain procedure, Wang needle biopsy, or fine needle aspiration (FNA) under bronchoscopic or CT guidance or other method Node positivity by FDG-PET scan Nodes > 3 cm on CT scan Paralyzed left true vocal cord with separate left lung primary distinct from AP window nodes on CT scan Stage IIIB patients must satisfy the following criteria; documentation of N3 or T4 status may be obtained by one or more of the following: Pathologically documented or radiographically documented positive N3 nodes; patients with positive supraclavicular or scalene lymph nodes must not have disease extending up into the cervical region Fine needle aspiration, core needle biopsy or excisional biopsy or supraclavicular N3 nodes Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy, mediastinotomy or thoracotomy Fine needle aspiration, core needle or Wang needle biopsy under Ct or bronchoscopic fluoroscopic guidance of enlarged contralateral N3 mediastinal nodes Contralateral mediastinal nodes > 3 cm on CT scan Node positivity by FDG-PET scan Right sided primary with paralyzed left true vocal cord OR Any of the following T4 lesions: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body or carina Written documentation of type of T4 extent by attending surgeon on either the operative report or as an addendum in the notes section of the prestudy form if patient has had an exploratory thoracotomy or thoracoscopy T4 involvement of trachea or carina by direct bronchoscopic visualization, documented on bronchoscopy report or as an addendum in the notes section of the prestudy form T4 involvement of heart, esophagus, aorta or vertebral body documented by CT scan, MRI or transesophageal ultrasound T4 involvement of the mediastinum may also be accepted by CT or MRI criteria if, in absence of the above organ involvement, there is soft tissue extension directly into the mediastinal space; radiographic criteria for involvement of main pulmonary artery or vein is allowed only if there is a mediastinal soft tissue mass Patients must not have malignant pleural effusions; NOTE: the only exception is pleural effusion only on CT scan (and not visible on CXR) OR deemed too small to tap Patients with pericardial effusions are ineligible All patients must have measurable or non-measurable disease documented by CT, MRI, X-ray or physical exam; measurable disease must be assessed within 28 days prior to registration and non-measurable disease assessed within 42 days prior to registration; pleural effusions and laboratory parameters are not acceptable as the only evidence of disease Patients must not have received any prior chemotherapy or radiotherapy for lung cancer; patients must not have had a previous surgical resection; however, patients may have undergone exploratory thoracotomy, mediastinoscopy, excisional biopsy or similar surgery for the purpose of determining diagnosis, stage, or potential resectability or newly diagnosed lung tumor Patients must have a measured or calculated creatinine clearance >= 50 cc/min The pre-registration FEV1 must be either >= 2.0 liters, OR if < 2.0 liters, the predicted FEV1 of the contralateral lung must be > 800 cc based on the quantitative split function testing within 42 days prior to registration WBC >= 3,000/ul ANC >= 1,200/ul Platelet count >= 100,000/ul All patients must have a CT of upper abdomen to exclude metastatic disease involving the contralateral chest, liver or adrenals (if chest CT is performed including complete liver and adrenals in the report, a separate CT of upper abdomen is not necessary) within 42 days prior to registration All patients must have a Zubrod Performance Status of 0-1 Patients must have an EKG within 42 days prior to registration Institutions must have received IRB approval for S9925; Southwest Oncology Group, NCIC-CTG and CTSU patients must be offered participation in S9925 (the Lung Cancer Specimen Repository); patients registered by other groups may be offered participation in S9925 (at the discretion of the participating group) No prior malignancy is allowed 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 five years If day 28 of 42 falls on a weekend or holiday, the limit may be extended to the next working day Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents; women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Sites / Locations

  • Southwest Oncology Group (SWOG) Research Base

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (gefitinib, combination chemotherapy, radiation)

Arm II (placebo, combination chemotherapy, radiation)

Arm Description

Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks. Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy. Patients receive oral gefitinib daily.

Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks. Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy. Patients receive oral placebo daily. In both arms, maintenance therapy continues for a maximum of 5 years in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall Survival
Progression-free survival

Secondary Outcome Measures

Full Information

First Posted
July 11, 2001
Last Updated
February 26, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00020709
Brief Title
Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
Official Title
A Phase III Trial of Cisplatin/Etoposide/Radiotherapy With Consolidation Docetaxel Followed by Maintenance Therapy With ZD1839 (NSC-715055) or Placebo in Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
June 2001 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Randomized phase III trial to compare the effectiveness of combination chemotherapy plus radiation therapy with or without gefitinib in treating unresectable stage III non-small cell lung cancer. Drugs used in chemotherapy use 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. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of tumors. It is not yet known whether combination chemotherapy plus radiation therapy is more effective with or without gefitinib in treating non-small cell lung cancer
Detailed Description
OBJECTIVES: I. To assess whether maintenance therapy with ZD1839 as compared to placebo following induction cisplatin/etoposide/radiotherapy plus consolidation docetaxel improves overall survival and progression-free survival in patients with unresectable Stage III non-small cell lung cancer (NSCLC). II. To describe the toxicity profile of long term administration of ZD1839. III. To obtain samples for correlative studies. OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to performance status (0 vs 1), stage (stage IIIA vs IIIB), measurability of lesion (measurable vs nonmeasurable), and histologic subtype (squamous vs nonsquamous). Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks. Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy. Arm I: Patients receive oral gefitinib daily. Arm II: Patients receive oral placebo daily. In both arms, maintenance therapy continues for a maximum of 5 years in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 5 years and then annually for 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
840 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (gefitinib, combination chemotherapy, radiation)
Arm Type
Experimental
Arm Description
Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks. Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy. Patients receive oral gefitinib daily.
Arm Title
Arm II (placebo, combination chemotherapy, radiation)
Arm Type
Experimental
Arm Description
Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks. Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy. Patients receive oral placebo daily. In both arms, maintenance therapy continues for a maximum of 5 years in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
RP 56976, Taxotere, TXT
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
gefitinib
Other Intervention Name(s)
Iressa, ZD 1839
Intervention Description
Given orally
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Other
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Overall Survival
Time Frame
From date of registration to date of death due to any cause, assessed up to 10 years
Title
Progression-free survival
Time Frame
From date of registration to date of first observation of progressive disease, death due to any cause, assessed up to 10 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Either histologic or cytologic proof of a newly diagnosed single, primary bronchogenic non-small cell lung cancer is required (adenocarcinoma, non-lobar and non-diffuse bronchioloalveolar cell carcinoma, large cell carcinoma, or squamous cell carcinoma); a biopsy with histology is preferred, but cytology is allowed; histology or cytology from involved mediastinal or supraclavicular lymph nodes alone will be allowed if a separate distal primary lesion is clearly evident on radiographs (i.e., a second biopsy will not be required) Patients with brain metastases are ineligible; all patients must have a pretreatment CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration Patients with two or more parenchymal lesions on same or opposite sides of the lung are ineligible Patients must have unresectable Stage IIIA (N2) or Stage IIIB disease and also satisfy the following criteria: Unresectable Stage IIIA (N2) patients must satisfy the criteria: N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or X-ray, such that, in the opinion of the treating investigator, the patient is not a candidate for induction chemotherapy or chemoradiotherapy followed by surgical resection If Stage IIIA (N2), the N2 status must be documented by any one of the following methods: Histologic or cytologic proof of N2 disease by exploratory thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy, Chamberlain procedure, Wang needle biopsy, or fine needle aspiration (FNA) under bronchoscopic or CT guidance or other method Node positivity by FDG-PET scan Nodes > 3 cm on CT scan Paralyzed left true vocal cord with separate left lung primary distinct from AP window nodes on CT scan Stage IIIB patients must satisfy the following criteria; documentation of N3 or T4 status may be obtained by one or more of the following: Pathologically documented or radiographically documented positive N3 nodes; patients with positive supraclavicular or scalene lymph nodes must not have disease extending up into the cervical region Fine needle aspiration, core needle biopsy or excisional biopsy or supraclavicular N3 nodes Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy, mediastinotomy or thoracotomy Fine needle aspiration, core needle or Wang needle biopsy under Ct or bronchoscopic fluoroscopic guidance of enlarged contralateral N3 mediastinal nodes Contralateral mediastinal nodes > 3 cm on CT scan Node positivity by FDG-PET scan Right sided primary with paralyzed left true vocal cord OR Any of the following T4 lesions: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body or carina Written documentation of type of T4 extent by attending surgeon on either the operative report or as an addendum in the notes section of the prestudy form if patient has had an exploratory thoracotomy or thoracoscopy T4 involvement of trachea or carina by direct bronchoscopic visualization, documented on bronchoscopy report or as an addendum in the notes section of the prestudy form T4 involvement of heart, esophagus, aorta or vertebral body documented by CT scan, MRI or transesophageal ultrasound T4 involvement of the mediastinum may also be accepted by CT or MRI criteria if, in absence of the above organ involvement, there is soft tissue extension directly into the mediastinal space; radiographic criteria for involvement of main pulmonary artery or vein is allowed only if there is a mediastinal soft tissue mass Patients must not have malignant pleural effusions; NOTE: the only exception is pleural effusion only on CT scan (and not visible on CXR) OR deemed too small to tap Patients with pericardial effusions are ineligible All patients must have measurable or non-measurable disease documented by CT, MRI, X-ray or physical exam; measurable disease must be assessed within 28 days prior to registration and non-measurable disease assessed within 42 days prior to registration; pleural effusions and laboratory parameters are not acceptable as the only evidence of disease Patients must not have received any prior chemotherapy or radiotherapy for lung cancer; patients must not have had a previous surgical resection; however, patients may have undergone exploratory thoracotomy, mediastinoscopy, excisional biopsy or similar surgery for the purpose of determining diagnosis, stage, or potential resectability or newly diagnosed lung tumor Patients must have a measured or calculated creatinine clearance >= 50 cc/min The pre-registration FEV1 must be either >= 2.0 liters, OR if < 2.0 liters, the predicted FEV1 of the contralateral lung must be > 800 cc based on the quantitative split function testing within 42 days prior to registration WBC >= 3,000/ul ANC >= 1,200/ul Platelet count >= 100,000/ul All patients must have a CT of upper abdomen to exclude metastatic disease involving the contralateral chest, liver or adrenals (if chest CT is performed including complete liver and adrenals in the report, a separate CT of upper abdomen is not necessary) within 42 days prior to registration All patients must have a Zubrod Performance Status of 0-1 Patients must have an EKG within 42 days prior to registration Institutions must have received IRB approval for S9925; Southwest Oncology Group, NCIC-CTG and CTSU patients must be offered participation in S9925 (the Lung Cancer Specimen Repository); patients registered by other groups may be offered participation in S9925 (at the discretion of the participating group) No prior malignancy is allowed 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 five years If day 28 of 42 falls on a weekend or holiday, the limit may be extended to the next working day Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents; women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen Kelly
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Oncology Group (SWOG) Research Base
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78245
Country
United States

12. IPD Sharing Statement

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Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

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