search
Back to results

Erlotinib and Radiation Therapy Plus Combination Chemotherapy in Treating Patients With Inoperable Stage III Non-Small Cell Lung Cancer

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cisplatin
etoposide
erlotinib hydrochloride
radiation therapy
docetaxel
paclitaxel
carboplatin
laboratory biomarker analysis
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

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

Inclusion Criteria: Histologically confirmed non-small cell lung cancer Squamous cell carcinoma Adenocarcinoma (including bronchoalveolar) Large cell carcinoma (including giant and clear cell carcinomas) Stage IIIA (T1 or T2, N2) or IIIB disease not amenable to resection or surgery T3, N2 or T4, N0-N2 disease also allowed if based on the closeness to the carina, invasion of the mediastinum, or invasion of the chest wall T3, N0-N1 disease allowed provided the disease is not amenable for surgical resection No M1 disease No disease invasion of a vertebral body Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiotherapy boost field and there is no bone invasion Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in the radiotherapy boost field Pleural effusion that is transudative, cytologically negative, and non-bloody allowed if the tumor can be encompassed in a reasonable field of radiotherapy No exudative, bloody, or cytologically malignant effusions Effusions present on CT scans but not on chest x-ray (CXR) and too small for thoracentesis are allowed Measurable or evaluable disease Pleural effusions are not considered measurable or evaluable Measurable disease is defined as any mass in 2 perpendicular diameters by CXR, CT scan, or MRI Evaluable disease includes lesions apparent on CXR or CT scan that are: Ill-defined masses associated with post-obstructive changes Mediastinal or hilar adenopathy measurable in only one dimension Performance status - ECOG 0-1 Performance status - Karnofsky 70-100% More than 6 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase normal AST and ALT normal and alkaline phosphatase no greater than 2.5 times ULN Creatinine normal Creatinine clearance at least 50 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No history of cornea abnormalities (e.g., dry-eye syndrome, Sjögren's syndrome) No congenital abnormality (e.g., Fuch's dystrophy) No abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose) No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test) No gastrointestinal tract disease resulting in the inability to take oral medications No required IV alimentation No peptic ulcer disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergy to compounds of similar chemical or biologic composition to erlotinib or other study agents No significant traumatic injury within the past 21 days No other uncontrolled concurrent illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other active malignancy within the past 6 months except non-melanoma skin cancer No concurrent colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) with radiotherapy No prior chemotherapy for lung cancer See Disease Characteristics No prior chest radiotherapy See Disease Characteristics At least 7 days since prior mediastinoscopy More than 3 weeks since prior formal exploratory thoracotomy More than 3 weeks since prior major surgery No prior surgical procedures affecting absorption No prior epidermal growth factor receptor-targeting therapies No other concurrent investigational or commercial agents or therapies directed at malignancy No concurrent combination antiretroviral therapy for HIV-positive patients

Sites / Locations

  • University of Chicago Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group I (cisplatin, etoposide, erlotinib, and docetaxel)

Group II (paclitaxel, carboplatin, and erlotinib

Arm Description

Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.

Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.

Outcomes

Primary Outcome Measures

MTD defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0

Secondary Outcome Measures

Response assessed using RECIST
Level of EGFR expression

Full Information

First Posted
August 5, 2002
Last Updated
January 31, 2013
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00042835
Brief Title
Erlotinib and Radiation Therapy Plus Combination Chemotherapy in Treating Patients With Inoperable Stage III Non-Small Cell Lung Cancer
Official Title
A Phase I Study Of OSI-774 (NSC #718781)-Based Multimodality Therapy For Inoperable Stage III Non Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Why Stopped
Administratively complete.
Study Start Date
May 2002 (undefined)
Primary Completion Date
December 2008 (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
Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and radiation therapy with combination chemotherapy may kill more tumor cells. Phase I trial to study the effectiveness of combining erlotinib and radiation therapy with combination chemotherapy in treating patients who have inoperable stage III non-small cell lung cancer
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of erlotinib that can be administered with chest radiotherapy in combination with cisplatin and etoposide or carboplatin and paclitaxel in patients with inoperable stage III non-small cell lung cancer. II. Determine the dose-limiting toxicity of these regimens in these patients. III. Assess the clinical response (complete response, partial response, progressive disease, or stable disease) in patients treated with these regimens. IV. Determine levels of tumor epidermal growth factor expression in patients treated with these regimens. OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to 1 of 2 treatment groups. GROUP 1: Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112. GROUP 2: Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43. In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib during concurrent chemoradiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. At least 12 patients from each group are treated at the MTD. Patients are followed at 8 weeks. PROJECTED ACCRUAL: A total of 24-48 patients (12-24 per treatment group) will be accrued for this study within 6-12 months.

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 1
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Arm Type
Experimental
Arm Description
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
Arm Title
Group II (paclitaxel, carboplatin, and erlotinib
Arm Type
Experimental
Arm Description
Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.
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)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
Given orally
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiotherapy
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)
paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, TAX, Taxol
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Carboplat, CBDCA, JM-8, Paraplat, Paraplatin
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
MTD defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
Time Frame
7 weeks
Secondary Outcome Measure Information:
Title
Response assessed using RECIST
Time Frame
Up to 8 weeks
Title
Level of EGFR expression
Time Frame
Up to 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed non-small cell lung cancer Squamous cell carcinoma Adenocarcinoma (including bronchoalveolar) Large cell carcinoma (including giant and clear cell carcinomas) Stage IIIA (T1 or T2, N2) or IIIB disease not amenable to resection or surgery T3, N2 or T4, N0-N2 disease also allowed if based on the closeness to the carina, invasion of the mediastinum, or invasion of the chest wall T3, N0-N1 disease allowed provided the disease is not amenable for surgical resection No M1 disease No disease invasion of a vertebral body Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiotherapy boost field and there is no bone invasion Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in the radiotherapy boost field Pleural effusion that is transudative, cytologically negative, and non-bloody allowed if the tumor can be encompassed in a reasonable field of radiotherapy No exudative, bloody, or cytologically malignant effusions Effusions present on CT scans but not on chest x-ray (CXR) and too small for thoracentesis are allowed Measurable or evaluable disease Pleural effusions are not considered measurable or evaluable Measurable disease is defined as any mass in 2 perpendicular diameters by CXR, CT scan, or MRI Evaluable disease includes lesions apparent on CXR or CT scan that are: Ill-defined masses associated with post-obstructive changes Mediastinal or hilar adenopathy measurable in only one dimension Performance status - ECOG 0-1 Performance status - Karnofsky 70-100% More than 6 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase normal AST and ALT normal and alkaline phosphatase no greater than 2.5 times ULN Creatinine normal Creatinine clearance at least 50 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No history of cornea abnormalities (e.g., dry-eye syndrome, Sjögren's syndrome) No congenital abnormality (e.g., Fuch's dystrophy) No abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose) No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test) No gastrointestinal tract disease resulting in the inability to take oral medications No required IV alimentation No peptic ulcer disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergy to compounds of similar chemical or biologic composition to erlotinib or other study agents No significant traumatic injury within the past 21 days No other uncontrolled concurrent illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other active malignancy within the past 6 months except non-melanoma skin cancer No concurrent colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) with radiotherapy No prior chemotherapy for lung cancer See Disease Characteristics No prior chest radiotherapy See Disease Characteristics At least 7 days since prior mediastinoscopy More than 3 weeks since prior formal exploratory thoracotomy More than 3 weeks since prior major surgery No prior surgical procedures affecting absorption No prior epidermal growth factor receptor-targeting therapies No other concurrent investigational or commercial agents or therapies directed at malignancy No concurrent combination antiretroviral therapy for HIV-positive patients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Mauer
Organizational Affiliation
University of Chicago Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Erlotinib and Radiation Therapy Plus Combination Chemotherapy in Treating Patients With Inoperable Stage III Non-Small Cell Lung Cancer

We'll reach out to this number within 24 hrs