Bortezomib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00027898
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 7, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of combining bortezomib with carboplatin and etoposide in treating patients who have advanced solid tumors that have not responded to previous treatment

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: bortezomib Drug: carboplatin Drug: etoposide Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:


I. Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy.

II. Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen.

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.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of PS-341 (NSC 681239), Carboplatin, and Etoposide in Patients With Advanced Solid Tumors Refractory to Standard Therapy
Study Start Date : January 2002
Actual Primary Completion Date : January 2006

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment (bortezomib, carboplatin, and etoposide)
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.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341

Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • JM-8
  • Paraplat
  • Paraplatin

Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

Other: laboratory biomarker analysis
Correlative studies

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Primary Outcome Measures :
  1. MTD defined as the dose level below the dose level that results in DLT in >= 2 of 6 new patients assessed using NCI CTC version 2.0 [ Time Frame: 21 days ]
  2. Biological data [ Time Frame: Up to 4 years ]
    The variation of these samples as a function of dose and time will be analyzed to define the mathematical function (e.g. linear, exponential, logistic) that best fits and models the data.

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed advanced solid tumor cancer for which no curativetherapy 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
  • Performance status - ECOG 0-2
  • At least 12 weeks
  • Absolute neutrophil count at least 1,500/mm^3
  • Hemoglobin at least 9 g/dL
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 mg/dL
  • AST/ALT no greater than 2.5 times upper limit of normal
  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 60 mL/min
  • 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)
  • No prior bone marrow or peripheral blood stem cell transplantation
  • No concurrent immunotherapy
  • 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
  • See Disease Characteristics
  • No concurrent hormonal therapy
  • 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
  • At least 28 days since prior investigational agents
  • No other concurrent experimental medications

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00027898

United States, Colorado
University of Colorado
Denver, Colorado, United States, 80217-3364
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Lia Gore University of Colorado, Denver

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00027898     History of Changes
Other Study ID Numbers: NCI-2012-02432
COMIRB 01-288
U01CA099176 ( U.S. NIH Grant/Contract )
CDR0000069091 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 7, 2013
Last Verified: February 2013

Additional relevant MeSH terms:
Etoposide phosphate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action