Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118183
First received: July 8, 2005
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This randomized phase II trial is studying how well giving docetaxel together with either cetuximab or bortezomib works as first-line therapy in treating patients with stage III or stage IV 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. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel together with either cetuximab or bortezomib may be effective as first-line therapy in treating non-small cell lung cancer.


Condition Intervention Phase
Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Large Cell Lung Cancer
Malignant Pleural Effusion
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: docetaxel
Biological: cetuximab
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Docetaxel Plus Cetuximab and Docetaxel Plus Bortezomib (NSC #681239, IND #58443) in Advanced Non-Small Cell Lung Cancer Patients With Performance Status (PS) 2

Resource links provided by NLM:


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

Primary Outcome Measures:
  • PFS [ Time Frame: Time between randomization and initial failure (disease progression or death), assessed up to 6 months ] [ Designated as safety issue: No ]
    The product limit estimator developed by Kaplan and Meier will be used.


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    An exact binomial 95% confidence interval will be computed for these estimates.

  • Overall survival [ Time Frame: Time between randomization and death, assessed up to 6 years ] [ Designated as safety issue: No ]
    The product limit estimator developed by Kaplan and Meier will be used.


Enrollment: 62
Study Start Date: July 2005
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive docetaxel IV over 30 minutes on days 1, 8, and 15 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive cetuximab alone as above in the absence of disease progression or unacceptable toxicity.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Experimental: Arm II
Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive bortezomib alone as above in the absence of disease progression or unacceptable toxicity.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression free survival (PFS), defined as the time between study entry and disease progression or death, for each of the two combination regimens.

SECONDARY OBJECTIVES:

I. To determine the overall response rate of each regimen. II. To evaluate the overall survival distributions associated with each regimen.

III. To evaluate the toxicities of each regimen.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive docetaxel IV over 30 minutes on days 1, 8, and 15 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive cetuximab alone as above 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 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive bortezomib alone as above in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed monthly for 1 year, every 2 months for 2 years, and then every 4 months for 3 years.

PROJECTED ACCRUAL: A total of 62 patients (31 per treatment arm) will be accrued for this study within 6-11 months.

  Eligibility

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

Inclusion Criteria:

  • All patients must have histologically or cytologically documented non-small cell carcinoma of the lung (adenocarcinoma, large cell, squamous, or mixtures of these types)
  • Patients with stage IV disease are eligible
  • Patients with stage IIIB due to a malignant pleural effusion or supraclavicular node involvement are eligible (IIIB patients eligible for CALGB protocols of combined chemotherapy and thoracic radiotherapy are not eligible)
  • Patients with known CNS metastases who have received therapy (surgery, XRT, gamma knife), and are neurologically stable and off steroids by the time of enrollment are eligible if they are not on enzyme-inducing anticonvulsants; patients with leptomeningeal disease are not eligible
  • Documentation of PS 2 must be noted on form C-1392
  • Patients must have measurable or non-measurable disease
  • Measurable disease (target lesions): lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
  • Non-measurable disease (non-target lesions): all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions; lesions that are considered non-measurable include the following:

    • Bone lesions
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
  • No prior systemic treatment for advanced NSCLC is permitted; prior treatment for early-stage disease (adjuvant) or for locally-advanced stage III disease is allowed if completed at least 12 months prior to registration
  • Patients must have recovered (all toxicities ≤ grade 1) from prior surgery and/or radiotherapy
  • No prior therapy which specifically and directly targets the EGFR pathway
  • No prior severe infusion reactions to a monoclonal antibody
  • No ≥ grade 2 peripheral neuropathy
  • Non-pregnant and non-nursing
  • No concurrent treatment with any other investigational therapy
  • Granulocytes ≥ 1,500/μl
  • Platelets ≥ 100,000/μl
  • Serum creatinine ≤ ULN
  • Bilirubin ≤ ULN
  • AST ≤ ULN
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118183

Locations
United States, Florida
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
Sponsors and Collaborators
Investigators
Principal Investigator: Rogerio Lilenbaum Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00118183     History of Changes
Other Study ID Numbers: NCI-2012-02820, CALGB-30402, U10CA031946
Study First Received: July 8, 2005
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Pleural Effusion
Pleural Effusion, Malignant
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pleural Diseases
Pleural Neoplasms
Docetaxel
Cetuximab
Bortezomib
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014