Bortezomib in Treating Patients With Advanced Non-small Cell Lung Cancer

A Phase II Study Of PS-341 In Metastatic Non-Small Cell Lung Cancer

Phase II trial to study the effectiveness of bortezomib in treating patients who have stage IIIB, stage IV, or recurrent non-small cell lung cancer. Bortezomib may interfere with the growth of tumor cells by blocking certain enzymes necessary for tumor cell growth

Study Overview

• Status: Terminated
• Conditions: Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: bortezomib

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the response rate, time to progression, and survival of patients with advanced non-small cell lung cancer treated with bortezomib.

II. Determine the toxicity of this drug in these patients. III. Correlate toxicity and activity of this drug with markers of proteasome inhibition in blood and peripheral mononuclear cells in these patients.

OUTLINE:

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who received prior bortezomib and achieved at least a partial response of at least 6 months duration may also receive therapy as above.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

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:

• Histologically or cytologically confirmed non-small cell lung cancer

  • Mixed tumors allowed unless small cell elements are present
• Stage IIIB or IV or recurrent disease
• At least 1 measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No known brain metastases
• Performance status - ECOG 0-1
• More than 3 months
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 2 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver involvement present)
• Creatinine ≤ 2 mg/dL
• Creatinine clearance ≥ 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No peripheral neuropathy > grade 1
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation

• No more than 1 prior chemotherapy regimen

  • Two prior chemotherapy regimens allowed provided 1 of the 2 regimens was gefitinib monotherapy as second-line therapy
• At least 4 weeks since prior chemotherapy (6 weeks for carmustine, mitomycin, or nitrosoureas) and recovered
• At least 4 weeks since prior radiotherapy (except localized radiotherapy for symptom relief) and recovered
• Prior bortezomib allowed provided patient achieved at least a partial response (of at least 6 months duration), received no other therapy since the last dose of bortezomib, and has no residual toxicity greater than grade 1
• No other concurrent investigational or commercial agents or therapies for malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (bortezomib); Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who received prior bortezomib and achieved at least a partial response of at least 6 months duration may also receive therapy as above.	Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall response rate to PS-341 therapy	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Kaplan-Meier estimates of survival (overall, progression free) and 95% confidence intervals will be calculated.	Up to 4 months
Overall survival	Kaplan-Meier estimates of survival (overall, progression free) and 95% confidence intervals will be calculated.	Up to 4 hours

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: James Stevenson, Abramson Cancer Center of the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: July 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 16, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

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; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCI-2012-02470; UPCC 06501; CDR0000069405 (Registry Identifier: PDQ (Physician Data Query))