Clinical trial NCT00042835: 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
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MTD defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
timeFrame: 7 weeks
Secondary outcomes:
measure: Response assessed using RECIST
timeFrame: Up to 8 weeks
measure: Level of EGFR expression
timeFrame: Up to 8 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Ann Mauer
role: PRINCIPAL_INVESTIGATOR
References: