Phase II Randomized Open-Label Trial of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Tarceva™) in Combination With Paclitaxel and Carboplatin Prior to Surgery in Resectable Stage IIIA (N2) and IIIB (T4 N2) NSCLC: A Clinical Outcome and Biological Endpoint Trial


Phase 2
N/A
N/A
Not Enrolling
Both
Lung Cancer

Thank you

Trial Information

Phase II Randomized Open-Label Trial of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Tarceva™) in Combination With Paclitaxel and Carboplatin Prior to Surgery in Resectable Stage IIIA (N2) and IIIB (T4 N2) NSCLC: A Clinical Outcome and Biological Endpoint Trial


This is a phase II, single institution open label randomized trial of induction carboplatin
and paclitaxel plus/minus daily oral OSI-774 in patients with potentially resectable NSCLC
that is stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no
malignant effusion.) N3 disease is excluded. Patients will be required to have
pathologically demonstrated N2 disease via mediastinoscopy. Forty patients will be treated
with 3 courses of chemotherapy followed by surgery. Ten of these patients will be
randomized to chemotherapy alone and 30 patients to chemotherapy plus OSI-774. The 10
patients will serve as a chemotherapy alone control for molecular endpoint analysis.
OSI-774 will be stopped the night before surgery. At the time of surgery, pathologic
response will be determined. Following surgery, patients will be treated with consolidation
radiation therapy if there are positive margins or N2 lymph nodes at the time of resection.
Patients who have no N2 disease at surgery will have the option of consolidation radiation
therapy but will not be required to have it done. Patients not able to tolerate radiation
even if they have N2 disease or positive margins at surgery may continue on this study. This
will be followed by maintenance OSI-774 for patients from both arms of the study. OSI-774
will be continued as maintenance to a maximum of 2 years following surgery. Tissue for
molecular studies will be obtained pretreatment either at the time of diagnostic biopsy or
mediastinoscopy. Post-treatment tissue will be obtained at the time of surgery. This
tissue will be assayed for defined molecular endpoints using immunohistochemistry,
immunoprecipitation and mRNA expression analysis. Blood, urine, hair follicles, and skin
samples will also be collected from patients who consent to provide these.


Inclusion Criteria:



1. Must have signed consent for LAB03-0383

2. Pathologic documentation of NSCLC

3. Stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no
malignant effusion) with all patients requiring mediastinoscopy positive N2,
potentially resectable disease. N3 disease is excluded.

4. Measurable disease

5. Zubrod performance status of 0 or 1

6. Calculated post-resectional FEV1 of > 40%

7. WBC>4000/l, ANC>1500/l, platelets > 100,000/l

8. Serum creatinine < 1.5 ULN or calculated creatinine > 50 cc/min

9. Total serum bilirubin <1.5 x ULN or SGPT or SGOT < 2 X ULN

10. The following must be completed within 28 days of registration: CT scan of the chest
and upper abdomen to include the adrenals. Mediastinoscopy to document ipsilateral
nodal involvement and exclude N3 disease Blood tests, and pulmonary function tests
The following must be completed within 2 months of registration: Pet scan If a CT PET
is done more than 28 days, only the CT needs to be repeated and a bone scan to rule
out bone metastases

Exclusion Criteria:

1. No prior chemotherapy or radiation for NSCLC

2. No prior malignancy is allowed except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, or other cancer from which the patient has
been disease-free for at least five years. If patient is suspected or known to have
basal or squamous skin cancer, this maybe treated after induction chemotherapy is
completed at the time of thoracotomy.

3. No post-obstructive pneumonia or other serious infection or other serious underlying
medical condition that would impair ability of patient to receive protocol treatment,
including prior allergic reactions to drugs containing cremophor.

4. Pregnant or nursing women may not participate

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients With Response

Outcome Description:

Response defined by tumor assessment using Response Evaluation Criteria In Solid Tumors (RECIST) to learn effectiveness of Tarceva (OSI-774) when combined with standard chemotherapy before surgery.

Outcome Time Frame:

5 Years to collect outcome information

Safety Issue:

No

Principal Investigator

Ralph Zinner, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

ID02-327

NCT ID:

NCT00063258

Start Date:

June 2003

Completion Date:

April 2008

Related Keywords:

  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Lung Cancer
  • OSI-774
  • Tarceva
  • Carboplatin
  • Paclitaxel
  • NSCLC
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location
MD Anderson Cancer Center Houston, Texas  77030-4096