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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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
Response assessed using RECIST
Condition
Adenocarcinoma of the Lung
Intervention
cisplatin
Study Arms / Comparison Groups
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
48
Start Date
May 2002
Primary Completion Date
December 2008
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ann Mauer, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00042835
Organization ID
NCI-2012-02478
Secondary IDs
11432B
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Ann Mauer, Principal Investigator, University of Chicago Comprehensive Cancer Center
Verification Date
January 2013