Clinical trial NCT00287989: Erlotinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official title: A Randomized Phase II Trial Comparing Two Doses of Pulsed Erlotinib Prechemotherapy (PEP-C) in Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-07
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving erlotinib together with paclitaxel and carboplatin may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying two different doses of erlotinib when given together with paclitaxel and carboplatin to compare how well they work in treating patients with stage III, stage IV, or recurrent non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Compare the major objective response (complete and partial response) rates in patients with stage IIIB or IV or recurrent non-small cell lung cancer treated with high- versus low-dose erlotinib hydrochloride combined with paclitaxel and carboplatin.
* Compare the duration of response, time to progression, and survival of patients treated with these regimens.
* Characterize and compare the toxicities of these regimens.
* Determine the recommended phase III dose of erlotinib hydrochloride.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to gender. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral high-dose erlotinib hydrochloride on days 1 and 2. Patients also receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 3.
* Arm II: Patients receive oral low-dose erlotinib hydrochloride, paclitaxel, and carboplatin as in arm I.

In both arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Pathologically confirmed non-small cell lung cancer

  * Stage IIIB or IV or recurrent disease
* Measurable or evaluable indicator lesions
* Must have smoked ≥ 100 cigarettes in his/her lifetime

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* WBC ≥ 4,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min
* Bilirubin ≤ 1.0 mg/dL
* AST ≤ 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 2.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 1 week after completion of study treatment
* No gastrointestinal tract disease or inability to take oral medication
* No prior malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
* No other active medical problems, including severe infection, unstable angina, or myocardial infarction within the past 6 months
* No poorly controlled hypertension or severe malnutrition
* No New York Heart Association class III or IV congestive heart failure or serious cardiac arrhythmia requiring medication except chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia)

PRIOR CONCURRENT THERAPY:

* At least 3 weeks since prior radiotherapy to major bone marrow-containing sites
* No prior chemotherapy for advanced non-small cell lung cancer
* No prior agents directed at the epidermal growth factor receptor (EGFR)/HER axis (e.g., gefitinib, cetuximab, or trastuzumab \[Herceptin®\])
* No prior surgical procedure resulting in abnormal absorption of oral medications
* No concurrent surgical resection, palliative radiotherapy, or hormonal therapy
* No other concurrent anticancer therapy

Primary outcomes:
measure: Overall Response Rate
timeFrame: after 6 cycles of chemotherapy
Secondary outcomes:
measure: Time to Progression
timeFrame: after cycle 6 of chemotherapy
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Charles M. Rudin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Riely GJ, Rizvi NA, Kris MG, Milton DT, Solit DB, Rosen N, Senturk E, Azzoli CG, Brahmer JR, Sirotnak FM, Seshan VE, Fogle M, Ginsberg M, Miller VA, Rudin CM. Randomized phase II study of pulse erlotinib before or after carboplatin and paclitaxel in current or former smokers with advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jan 10;27(2):264-70. doi: 10.1200/JCO.2008.17.4656. Epub 2008 Dec 1.