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

Randomized Phase II Trial of Sequential Versus Concurrent Docetaxel and PS-341 (NSC 681239) in Previously Treated Non-Small Cell Lung Cancer (NSCLC)

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

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: bortezomib; Other: pharmacological study; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Other: immunohistochemistry staining method

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Criteria:

• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for 5 years.
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Progressive or recurrent NSCLC after treatment with 1 prior platinum-based chemotherapy regimen for metastatic disease. Prior neoadjuvant/adjuvant chemotherapy and/or concurrent chemoradiation for early-stage disease allowed.
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered.
• No prior docetaxel or bortezomib
• Prior epidermal growth factor receptor inhibitor therapy allowed.
• Prior paclitaxel allowed
• At least 4 weeks since prior major surgery and recovered.
• At least 2 weeks since prior and no concurrent enzyme-inducing anticonvulsants.
• No concurrent hormonal therapy, biologic therapy, or radiotherapy to measurable lesions. Concurrent palliative radiotherapy to small-field nonindicator lesions (e.g., painful bony metastases) allowed.
• Measurable disease* with >= 1 unidimensionally objectively measurable lesion, including any of the following:
• Lung mass (measurable on chest x-ray, tomograms, or CT scan)
• Enlarged lymph nodes
• Liver metastasis (measurable as a discrete focal lesion on radionuclide or CT scan, or ultrasound)
• Metastatic abdominal mass (measurable on CT scan with >= 1 perpendicular diameter ≥ the distance between cuts)
• Measurable disease must be outside the previous radiation field or a new lesion must be present.
• Life expectancy >= 12 weeks
• Progressive disease within a previously radiated field allowed.
• [Note: *Measurable disease DOES NOT include bone metastases or non-focal liver metastases].
• No symptomatic or untreated brain metastasis requiring steroids. Asymptomatic, previously treated (surgical resection or radiotherapy) brain metastasis allowed provided they are neurologically stable and >= 4 weeks since prior steroids.
• Creatinine clearance >= 50 mL/min
• Creatinine =< 1.6 mg/dL
• Bilirubin normal
• AST =< 2 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No peripheral neuropathy >= grade 2
• Absolute granulocyte count >= 1,500/mm³
• Platelet count >= 100,000/mm³
• Cutaneous nodule
• ECOG performance status 0-1
• At least 4 weeks since prior radiotherapy and recovered.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8.	Drug: docetaxel; Given IV; Other Names: Taxotere; RP 56976; TXT; Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE; Other: pharmacological study; correlative study; Other Names: pharmacological studies; Other: laboratory biomarker analysis; correlative study; Other: immunoenzyme technique; correlative study; Other Names: immunoenzyme techniques; Other: immunohistochemistry staining method; correlative study; Other Names: immunohistochemistry
Experimental: Arm 2; Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8.	Drug: docetaxel; Given IV; Other Names: Taxotere; RP 56976; TXT; Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE; Other: pharmacological study; correlative study; Other Names: pharmacological studies; Other: laboratory biomarker analysis; correlative study; Other: immunoenzyme technique; correlative study; Other Names: immunoenzyme techniques; Other: immunohistochemistry staining method; correlative study; Other Names: immunohistochemistry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	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	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Will be estimated using the product-limit method of Kaplan and Meier.	From first day of treatment to time of death due to any cause, up to 4 years
Disease Control Rate	Disease control rate was defined as the rate of partial response (PR) plus stable disease (SD; for at least 2 cycles).	Up to 4 years
Progression-free Survival @ 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.	6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Primo Lara, University of California, Davis

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 10, 2006
• First Submitted That Met QC Criteria: August 10, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Actual): December 5, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Bortezomib
• Other Study ID Numbers: NCI-2009-00123; N01CM17101 (U.S. NIH Grant/Contract); PHII-70; CDR0000491470 (Registry Identifier: PDQ (Physician Data Query))