Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00066625
• Other study ID #: NCI-2012-02552
• Secondary ID: NYU 02-12N01CM62
• Status: Terminated
• Phase: Phase 1
• First received: August 6, 2003
• Last updated: January 31, 2013
• Start date: July 2003

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase I trial to study the effect on the body of combining oxaliplatin with bortezomib in treating patients who have metastatic or unresectable cancer. Drugs used in chemotherapy such as oxaliplatin use different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for tumor cell growth. Combining oxaliplatin with bortezomib may kill more cancer cells

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• oxaliplatin
Given IV
• bortezomib
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Up to 28 days	Yes
Secondary	Area under the curve (AUC) estimates	Nonlinear compartmental analysis of the oxaliplatin pharmacokinetic data will be performed.	Days 1 and 15 (course 1)	No
Secondary	Pharmacodynamic assessments (20S proteasome inhibition data)	Summarized by dose and time using standard descriptive statistics. Asssessments will correlate the AUC in an Emax inhibitory model.	Days 1 and 15 (course 1)	No
Secondary	Sequence of drug administration in terms of PK interaction	AUC for oxaliplatin and 20-S proteasome inhibition will be calculated and compared for intra-patient variation using paired T-test.	Days 1 and 15 (course 1)	No