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

NCT ID: NCT00042835

Last Updated: 2013-02-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

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 Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

Given IV

etoposide

Intervention Type: DRUG

Given IV

erlotinib hydrochloride

Intervention Type: DRUG

Given orally

radiation therapy

Intervention Type: RADIATION

Undergo radiotherapy

docetaxel

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Group II (paclitaxel, carboplatin, and erlotinib

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.

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

Given orally

radiation therapy

Intervention Type: RADIATION

Undergo radiotherapy

paclitaxel

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

cisplatin

Given IV

Intervention Type: DRUG

etoposide

Given IV

Intervention Type: DRUG

erlotinib hydrochloride

Given orally

Intervention Type: DRUG

radiation therapy

Undergo radiotherapy

Intervention Type: RADIATION

docetaxel

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

carboplatin

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

CACP; CDDP; CPDD; DDP; EPEG; VP-16; VP-16-213; CP-358,774; erlotinib; OSI-774; irradiation; radiotherapy; therapy, radiation; RP 56976; Taxotere; TXT; Anzatax; Asotax; TAX; Taxol; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann Mauer

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

11432B

Identifier Type: -

Identifier Source: secondary_id

N01CM17102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069474

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02478

Identifier Type: -

Identifier Source: org_study_id