Clinical trial NCT00278148: Erlotinib, Paclitaxel, and Carboplatin Combined With Radiation Therapy for Stage III Non-Small Cell Lung Cancer
Official title: A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib, paclitaxel, and carboplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase I/II trial is studying the best dose of erlotinib and the side effects of erlotinib, paclitaxel, and carboplatin when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for stage III non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Assess the safety and feasibility of erlotinib hydrochloride, paclitaxel, and carboplatin in combination with accelerated hyperfractionated radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer.
* Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients.
* Assess the safety and tolerability of long-term maintenance erlotinib hydrochloride after completion of adjuvant chemoradiotherapy in these patients.

Secondary

* Evaluate the clinical and pathological response rate in these patients after neoadjuvant erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy.
* Assess the impact of erlotinib hydrochloride on disease-free survival, overall survival, locoregional control, and distant metastatic control in these patients.

OUTLINE: This is an open-label, phase I dose-escalation study of erlotinib hydrochloride followed by a non-randomized phase II study.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Phase I:

  * Neoadjuvant chemoradiotherapy: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15 in the absence of disease progression or unacceptable toxicity. Patients concurrently undergo radiotherapy twice daily on days 1-5 and 8-12. Patients with complete response, partial response, or stable disease proceed to surgery. Patients who develop a medical contraindication to surgery (i.e., medically unresectable) receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as above within 2 weeks after completion of neoadjuvant chemoradiotherapy.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Surgery: Within 4 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection and then proceed to adjuvant chemoradiotherapy.
* Adjuvant chemoradiotherapy: Within 6-8 weeks after surgery, patients receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as in neoadjuvant chemoradiotherapy.
* Maintenance therapy: All patients receive oral erlotinib hydrochloride once daily for 2 years in the absence of disease progression or unacceptable toxicity.

  * Phase II: Patients receive treatment as in phase I with erlotinib hydrochloride at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer

  * Surgically determined stage IIIA or IIIB disease
  * Histology from an involved mediastinal or supraclavicular lymph nodes alone will be allowed if a separate distal primary lesion is clearly evident on radiographs

    * Histological or cytological proof of mediastinal nodal involvement by mediastinoscopy, Chamberlain procedure, thoracoscopy, thoracotomy, or CT-guided biopsy is required except for cases of paralysis of left true vocal cord with separate left lung primary distinct from enlarged nodes \> 1 cm in the anterior-posterior window seen on the CT scan
* Patients with N3 or T4 status must be evaluated and deemed potentially resectable after induction chemotherapy and radiation therapy
* Measurable and evaluable disease
* No malignant pleural effusion except for effusion visible only on CT scan and deemed too small to tap
* No pericardial effusion
* No small or mixed small cell/non-small cell lung cancer
* No massive lesions requiring radiation to the entire lung
* No metastatic cancer to the lungs

PATIENT CHARACTERISTICS:

* ECOG performance status 0-1
* WBC ≥ 3,000/mm\^3
* Platelet count \> 100,000/mm\^3
* Serum creatinine ≤ 2.0 mg/dL
* Alkaline phosphatase, AST, and ALT \< 2 times upper limit of normal
* Albumin \> 3.0 g/dL
* Serum bilirubin \< 1.5 mg/dL
* Adequate pulmonary function
* No clinical evidence of another uncontrolled malignancy
* No requirement for urgent therapy for severe local symptoms such as post-obstructive pneumonia

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy, radiation therapy, or immunotherapy for lung cancer
* No prior surgery to treat the cancer

Primary outcomes:
measure: Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)
timeFrame: 2 weeks after surgery
measure: Tolerability of Long-term OSI-774 (Phase II)
timeFrame: 2 years
Secondary outcomes:
measure: Pathological Complete Response Rate
timeFrame: 2 years
measure: Overall Survival
timeFrame: 3 years
measure: Progression Free Survival (PFS)
timeFrame: 3 years
measure: Locoregional Control
timeFrame: 2 years
measure: Distant Control
timeFrame: 2 years
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Nathan Pennell, MD
role: STUDY_CHAIR
References: