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

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

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.

Study Overview

• Status: Completed
• Conditions: Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Adenocarcinoma of the Lung; Large Cell Lung Cancer; Malignant Pleural Effusion; Adenosquamous Cell Lung Cancer
• Intervention / Treatment: Biological: cetuximab; Drug: docetaxel; Drug: bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: cetuximab; Given IV; Other Names: C225; IMC-C225; C225 monoclonal antibody; MOAB C225; monoclonal antibody C225; Drug: docetaxel; Given IV; Other Names: Taxotere; RP 56976; TXT
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: Taxotere; RP 56976; TXT; Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	The product limit estimator developed by Kaplan and Meier will be used.	Time between randomization and initial failure (disease progression or death), assessed up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	An exact binomial 95% confidence interval will be computed for these estimates.	Up to 6 years
Overall survival	The product limit estimator developed by Kaplan and Meier will be used.	Time between randomization and death, assessed up to 6 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Rogerio Lilenbaum, Cancer and Leukemia Group B

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (ACTUAL): April 1, 2007

Study Registration Dates

• First Submitted: July 8, 2005
• First Submitted That Met QC Criteria: July 8, 2005
• First Posted (ESTIMATE): July 11, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pleural Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Pleural Effusion, Malignant; Pleural Effusion; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Antibodies; Immunoglobulins; Bortezomib; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: NCI-2012-02820; U10CA031946 (U.S. NIH Grant/Contract); CALGB-30402