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A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer

Phase 1
18 Years
Not Enrolling
Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer


I. Determine the safety and feasibility of combining bortezomib with gemcitabine and
carboplatin in patients with advanced or recurrent non-small cell lung cancer.

II. Determine the maximum tolerated dose of bortezomib administered in combination with
gemcitabine and carboplatin in these patients.

III. Correlate results from laboratory studies on patient tissue and serum specimens with
potential predictors of response in patients treated with this regimen.

IV. Determine, preliminarily, the response of patients treated with this regimen.

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.

Inclusion Criteria:

- 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

- Performance status - Karnofsky 60-100%

- More than 3 months

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.5 mg/dL

- AST no greater than 2.5 times upper limit of normal

- Creatinine normal

- Creatinine clearance at least 50 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 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

- No concurrent routine filgrastim (G-CSF)

- See Disease Characteristics

- No more than 1 prior chemotherapy regimen

- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and

- No prior gemcitabine

- See Disease Characteristics

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

- See Disease Characteristics

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicities at each dose level, graded using the CTC version 2.0

Outcome Description:

Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, (by NCI Common Toxicity Criteria and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.

Outcome Time Frame:

18 weeks

Safety Issue:


Principal Investigator

Angela Davies

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 2002

Completion Date:

Related Keywords:

  • Malignant Pleural Effusion
  • Recurrent Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Pleural Effusion
  • Pleural Effusion, Malignant



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