Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	CCC-PHI-40 CHNMC-PHI-40, NCI-5856, 5856, NCT00052338

Objectives

1. Determine the safety and feasibility of combining bortezomib with gemcitabine and carboplatin in patients with advanced or recurrent non-small cell lung cancer.
2. Determine the maximum tolerated dose of bortezomib administered in combination with gemcitabine and carboplatin in these patients.
3. Correlate results from laboratory studies on patient tissue and serum specimens with potential predictors of response in patients treated with this regimen.
4. Determine, preliminarily, the response of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed non-small cell lung cancer
  • Selected stage IIIB (malignant pleural effusion) or stage IV disease
  • Recurrent disease after first-line therapy allowed
• Patients who received prior platinum-based chemotherapy must have no disease progression during or within 3 months after completion of therapy
  • Patients who are enrolled at the maximum tolerated dose must have chemotherapy-naïve disease
• Evaluable disease
• Asymptomatic brain metastases allowed if treated with surgical resection or radiotherapy, neurologically stable, and off steroids for at least 4 weeks

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent routine filgrastim (G-CSF)

Chemotherapy

• See Disease Characteristics
• No more than 1 prior chemotherapy regimen
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No prior gemcitabine

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics

Other

• More than 30 days since prior investigational drugs
• No prior bortezomib
• No concurrent anticonvulsant therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies with intent to treat malignancy

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than than 1.5 mg/dL
• AST no greater than 2.5 times upper limit of normal

Renal

• Creatinine normal

  OR

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No peripheral neuropathy grade 2 or greater
• No prior allergic reactions to compounds of similar chemical or biological composition to bortezomib or other agents used in this study
• No concurrent ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

A total of 25-34 patients will be accrued for this study.

Outline

This is a multicenter, dose-escalation study of bortezomib.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, followed 1 hour later by bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a clinical or radiographic response may continue receiving bortezomib beyond 6 courses.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, at least 10 additional patients with chemotherapy-naive disease receive treatment as above with the MTD of bortezomib.

Patients are followed for survival.

Davies AM, Ruel C, Lara PN, et al.: The proteasome inhibitor bortezomib in combination with gemcitabine and carboplatin in advanced non-small cell lung cancer: a California Cancer Consortium Phase I study. J Thorac Oncol 3 (1): 68-74, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

California Cancer Consortium

Angela Davies, MD, Protocol chair		Ph: 916-734-3771

Registry Information
Official Title		A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer
Trial Start Date		2002-12-06
Registered in ClinicalTrials.gov		NCT00052338
Date Submitted to PDQ		2002-09-27
Information Last Verified		2004-07-16
NCI Grant/Contract Number		CA33572, CM17107

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