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

Alternate Title

Bortezomib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 16 and over NCI UCHSC-COMIRB-01288 NCI-3171, NCT00027898, 3171

Objectives

1. Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy.
2. Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed advanced solid tumor cancer for which no curative therapy exists



• Clinically stable CNS disease is allowed provided the following criteria are met:
  • No uncontrolled brain metastases or CNS involvement
  • No active seizures
  • On stable dose of antiseizure or steroid medication for at least 7 days before study enrollment

Prior/Concurrent Therapy:

Biologic therapy:

• No prior bone marrow or peripheral blood stem cell transplantation
• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior carboplatin and/or etoposide allowed
• No more than 2 prior courses of mitomycin

Endocrine therapy:

• See Disease Characteristics
• No concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• Palliative radiotherapy involving less than 35% bone marrow reserve allowed if completed at least 2 weeks before study enrollment
• No prior wide-field radiotherapy to 35% or more of bone marrow
• No prior pelvic radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• At least 28 days since prior investigational agents
• No other concurrent experimental medications

Patient Characteristics:

Age:

• 16 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm³

Hepatic:

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

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No other serious concurrent systemic disorders (including other malignancy)

Expected Enrollment

A total of 12-27 patients will be accrued for this study within 6-14 months.

Outline

This is a dose-escalation study of bortezomib, etoposide, and carboplatin.

Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

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 or more of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients with newly diagnosed, chemotherapy-naive extensive stage small cell lung cancer, and 6 patients with other tumor types, are treated at that dose.

Gore L, Witta S, Pierson AS, et al.: A phase I study of PS-341 (P), carboplatin (C), and etoposide (E) in patients (pts) with advanced solid tumors. [Abstract] Clin Cancer Res 9: A-C74, 6221s, 2003.

Trial Contact Information

Trial Lead Organizations

University of Colorado Cancer Center at UC Health Sciences Center

Lia Gore, MD, FAAP, Principal investigator		Ph: 303-724-4011; 800-473-2288 Email: lia.gore@uchsc.edu

Registry Information
Official Title		A Phase I Study of PS-341 (NSC 681239), Carboplatin, and Etoposide in Patients with Advanced Solid Tumors Refractory to Standard Therapy
Trial Start Date		2001-09-26
Registered in ClinicalTrials.gov		NCT00027898
Date Submitted to PDQ		2001-10-16
Information Last Verified		2005-12-15
NCI Grant/Contract Number		P30-CA46934

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