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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lung Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of erlotinib hydrochloride (Phase I)

Outcome Description:

The Phase I portion of this study is to determine the Maximum Tolerated Dose (MTD) of combining OSI-774 with the paclitaxel-carboplatin chemoradiation protocol and to assess the safety and feasiblity of this combination.

Outcome Time Frame:

2 weeks after surgery

Safety Issue:

Yes

Principal Investigator

Nathan Pennell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CCF5876

NCT ID:

NCT00278148

Start Date:

October 2005

Completion Date:

December 2012

Related Keywords:

  • Lung Cancer
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterCleveland, Ohio  44195