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A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy


OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and
bortezomib in patients with advanced malignancy.

II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine
the toxicity profile of this regimen in these patients. IV. Determine the antitumor activity
of this regimen in these patients. V. Determine the pattern of neurotoxicity and its
reversibility in patients responding to prolonged administration of this treatment regimen.

VI. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib
are altered by the administration of the other agent in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5
seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.

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

Patients are followed for at least 3 months.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-15
months.


Inclusion Criteria:



- Histologically confirmed malignancy for which standard curative or palliative
measures do not exist or are no longer effective

- Metastatic or unresectable disease

- No known brain metastases

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100

- More than 6 months

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

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

- Bilirubin normal

- AST and ALT no greater than 5 times upper limit of normal

- Creatinine no greater than 1.5 mg/dL

- 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 history of allergic reactions attributed to compounds of similar chemical or
biological composition to any platinum or other study agents

- No pre-existing peripheral neuropathy

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other concurrent uncontrolled illness

- Prior thalidomide allowed provided patient has no clinical neuropathy

- Prior platinum or antitubulin agents allowed provided patient has no clinical
neuropathy

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
and recovered

- More than 3 weeks since prior radiotherapy and recovered

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational or commercial agents or therapies for the
malignancy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Probability of dose escalation according to true dose limiting toxicity (DLT) rate, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

Outcome Time Frame:

Up to 28 days

Safety Issue:

Yes

Principal Investigator

Howard Hochster

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02552

NCT ID:

NCT00066625

Start Date:

July 2003

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific

Name

Location
Montefiore Medical Center Bronx, New York  10467-2490