Docetaxel and Bortezomib in Treating Patients With Progressive or Recurrent Non-Small Cell Lung Cancer

Phase 2

Completed

Conditions: Non-small Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer

Interventions: Drug: docetaxel
Drug: bortezomib
Other: laboratory biomarker analysis
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: pharmacological study

Registration Number: NCT00362882

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This trial is studying two different schedules of docetaxel and bortezomib to compare how well they work in treating patients with progressive or recurrent non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel together with bortezomib may kill more tumor cells

Detailed Description: PRIMARY OBJECTIVE:

I. To compare the efficacy and tolerability of sequential vs concurrent docetaxel and bortezomib in patients with previously treated, progressive or recurrent, advanced non-small cell lung cancer (NSCLC).

SECOND OBJECTIVES:

I. To compare time to progression in patients with previously treated NSCLC treated with these regimens.

II. To compare 1-year and overall survival of patients treated with these regimens.

III. To compare the toxicity of these regimens in these patients. IV. To determine the pharmacokinetics of docetaxel in the context of this study.

TERTIARY OBJECTIVE:

I. To determine levels of expression of molecular markers regulated by docetaxel and bortezomib and correlate with clinical response and overall survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1) and number of prior chemotherapy treatments (1 vs \>1). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	docetaxel	Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.
Arm 1	laboratory biomarker analysis	Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.
Arm 1	immunoenzyme technique	Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.
Arm 1	immunohistochemistry staining method	Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.
Arm 1	pharmacological study	Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.
Arm 2	laboratory biomarker analysis	Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.
Arm 2	immunoenzyme technique	Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.
Arm 2	immunohistochemistry staining method	Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.
Arm 2	pharmacological study	Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.
Arm 2	bortezomib	Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.
Arm 1	bortezomib	Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.
Arm 2	docetaxel	Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Up to 4 years	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From first day of treatment to time of death due to any cause, up to 4 years	Will be estimated using the product-limit method of Kaplan and Meier.
Disease Control Rate	Up to 4 years	Disease control rate was defined as the rate of partial response (PR) plus stable disease (SD; for at least 2 cycles).
Progression-free Survival @ 6 Months	6 months	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.