Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	UCCRC-11432 NCI-5411, NCT00042835, 5411

Objectives

1. 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.
2. Determine the dose-limiting toxicity of these regimens in these patients.
3. Assess the clinical response (complete response, partial response, progressive disease, or stable disease) in patients treated with these regimens.
4. Determine levels of tumor epidermal growth factor expression in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) with radiotherapy

Chemotherapy

• No prior chemotherapy for lung cancer

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior chest radiotherapy

Surgery

• 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

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

  OR

• Karnofsky 70-100%

Life expectancy

• More than 6 months

Hematopoietic

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin normal
• AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase normal

  OR

• AST and ALT normal and alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine normal

  OR

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Ophthalmic

• 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)

Gastrointestinal

• No gastrointestinal tract disease resulting in the inability to take oral medications
• No required IV alimentation
• No peptic ulcer disease

Other

• 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

Expected Enrollment

A total of 24-48 patients (12-24 per treatment group) will be accrued for this study within 6-12 months.

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.

Choong NW, Mauer AM, Haraf DJ, et al.: Phase I trial of erlotinib-based multimodality therapy for inoperable stage III non-small cell lung cancer. J Thorac Oncol 3 (9): 1003-11, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Ann Mauer, MD, Protocol chair		Ph: 773-702-4138; 888-824-0200

Registry Information
Official Title		A Phase I Study Of OSI-774 (NSC #718781)-Based Multimodality Therapy For Inoperable Stage III Non Small Cell Lung Cancer
Trial Start Date		2002-05-23
Trial Completion Date		2008-12-22
Registered in ClinicalTrials.gov		NCT00042835
Date Submitted to PDQ		2002-06-03
Information Last Verified		2005-09-20
NCI Grant/Contract Number		N01-CM17102, P30-CA14599

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