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

Alternate Title

Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI NYU-0212 NCI-5736, 5736, NCT00066625

Objectives

1. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and bortezomib in patients with advanced malignancy.
2. Determine the dose-limiting toxicity of this regimen in these patients.
3. Determine the toxicity profile of this regimen in these patients.
4. Determine the antitumor activity of this regimen in these patients.
5. Determine the pattern of neurotoxicity and its reversibility in patients responding to prolonged administration of this treatment regimen.
6. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib are altered by the administration of the other agent in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Prior thalidomide allowed provided patient has no clinical neuropathy

Chemotherapy

• 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

Endocrine therapy

• Not specified

Radiotherapy

• More than 3 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies for the malignancy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100

Life expectancy

• More than 6 months

Hematopoietic

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

Hepatic

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

Renal

• Creatinine no greater than 1.5 mg/dL

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 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

Expected Enrollment

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

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.

Kobrinsky B, Kosloff RA, Wright J, et al.: Neurotoxicity assessment in a phase I bortezomib with oxaliplatin trial. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-951, 2007.

Kosloff RA, Wright J, Ivy P, et al.: Phase I study of bortezomib and oxaliplatin (BOX) in solid tumors: improved neurotoxicity (NT) profile with lower bortezomib (B) dose. [Abstract] J Clin Oncol 24 (Suppl 18): A-12007, 596s, 2006.

Trial Contact Information

Trial Lead Organizations

NYU Cancer Institute at New York University Medical Center

Howard Hochster, MD, Principal investigator		Ph: 212-731-5100 Email: howard.hochster@med.nyu.edu

Registry Information
Official Title		A Phase I And Pharmacokinetic Study Of Oxaliplatin (EloxatinTM) In Combination With Bortezumib (PS-341, VELCADETM) In Patients With Advanced Malignancy
Trial Start Date		2003-10-06
Registered in ClinicalTrials.gov		NCT00066625
Date Submitted to PDQ		2003-06-27
Information Last Verified		2007-01-15
NCI Grant/Contract Number		CA16087, CM17103

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