Trial Information

Phase I/II Study of PS-341 in Combination With Paclitaxel, Carboplatin, and Concurrent Thoracic Radiation Therapy for Non-Small Cell Lung Cancer (NSCLC)

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib, paclitaxel, and carboplatin when
administered with fractionated radiotherapy in patients with unresectable stage IIIA or IIIB
non-small cell lung cancer. (Phase I) (closed to accrual as of 09/29/2009) II. Determine the
1-year survival of patients treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the tolerability of this regimen in these patients. (Phase II) II. Determine
the response rate, progression-free survival, and overall survival of patients treated with
this regimen. (Phase II) III. Correlate p27 expression in tumor tissue with survival, time
to progression, and response in patients treated with this regimen. (Phase II)

OUTLINE: This is a multicenter, phase I (closed to accrual as of 09/29/2009),
dose-escalation study of bortezomib, paclitaxel, and carboplatin followed by a phase II
study.

PHASE I: (closed to accrual as of 09/29/2009) Patients receive bortezomib IV on days 1, 4,
8, and 11. Patients also receive paclitaxel IV over 3 hours followed by carboplatin IV over
30 minutes on day 2. Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19.
Treatment repeats every 3 weeks up to 2 courses in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib,
paclitaxel, and carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 6 patients experience dose-limiting
toxicity.

PHASE II: Patients receive bortezomib, paclitaxel, and carboplatin as in phase I at the MTD.
Patients also undergo radiotherapy as in phase I. Patients are followed up periodically for
up to 5 years from the time of registration.