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Docetaxel and Bortezomib in Treating Patients With Progressive or Recurrent Non-Small Cell Lung Cancer
This study is ongoing, but not recruiting participants.
First Received: August 10, 2006   Last Updated: May 13, 2009   History of Changes
Sponsors and Collaborators: California Cancer Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00362882
  Purpose

RATIONALE: 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. It is not yet known which schedule of docetaxel and bortezomib is more effective in treating non-small cell lung cancer.

PURPOSE: This randomized phase II 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.


Condition Intervention Phase
Lung Cancer
Drug: bortezomib
Drug: docetaxel
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: Randomized Phase II Trial of Sequential Versus Concurrent Docetaxel and PS-341 (NSC 681239, IND 58,443) in Previously Treated Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Efficacy and tolerability of 2 schedules of docetaxel and bortezomib [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • 1-year and overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: July 2006
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental

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.

Drug: bortezomib
given IV
Drug: docetaxel
given IV
Arm II: Experimental
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.
Drug: bortezomib
given IV
Drug: docetaxel
given IV

Detailed Description:

OBJECTIVES:

Primary

  • 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).

Secondary

  • Compare time to progression in patients with previously treated NSCLC treated with these regimens.
  • Compare 1-year and overall survival of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Determine the pharmacokinetics of docetaxel in the context of this study.

Tertiary

  • 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.

Tumor and blood samples are collected periodically for biomarker analysis and pharmacokinetic assays.

Immunohistochemistry is used to assess Bcl-2, Bcl-xL, Bax, and NF-kB. Immunoenzyme techniques are used to examine hypoxia-inducible factor 1 (HIF-1), OPN, vascular endothelial growth factor, and PAI-1.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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
  • Measurable disease* with ≥ 1 unidimensionally objectively measurable lesion, including any of the following:

    • Lung mass (measurable on chest x-ray, tomograms, or CT scan)
    • Cutaneous nodule
    • 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

      • 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

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • 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
  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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 radiotherapy and recovered
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00362882

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
California Cancer Consortium
Investigators
Study Chair: Primo N. Lara, MD University of California, Davis
  More Information

Additional Information:
No publications provided

Responsible Party: University of California Davis Cancer Center ( David R. Gandara )
Study ID Numbers: CDR0000491470, CCC-PHII-70, NCI-7077
Study First Received: August 10, 2006
Last Updated: May 13, 2009
ClinicalTrials.gov Identifier: NCT00362882     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer

Study placed in the following topic categories:
Docetaxel
Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Bortezomib
Non-small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung
Recurrence
Protease Inhibitors
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Bortezomib
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors
Carcinoma
Docetaxel
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 02, 2009