Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer

• ClinicalTrials.gov Identifier: NCT00066625
• Recruitment Status: Terminated
• First Posted: August 7, 2003
• Last Update Posted: February 1, 2013
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: August 6, 2003
• First Posted Date: August 7, 2003
• Last Update Posted Date: February 1, 2013
• Study Start Date: July 2003
• Actual Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 31, 2013): 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 [ Time Frame: Up to 28 days ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: January 31, 2013)

• Area under the curve (AUC) estimates [ Time Frame: Days 1 and 15 (course 1) ]
  Nonlinear compartmental analysis of the oxaliplatin pharmacokinetic data will be performed.
• Pharmacodynamic assessments (20S proteasome inhibition data) [ Time Frame: Days 1 and 15 (course 1) ]
  Summarized by dose and time using standard descriptive statistics. Asssessments will correlate the AUC in an Emax inhibitory model.
• Sequence of drug administration in terms of PK interaction [ Time Frame: Days 1 and 15 (course 1) ]
  AUC for oxaliplatin and 20-S proteasome inhibition will be calculated and compared for intra-patient variation using paired T-test.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer
• Official Title: A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy
• Brief 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

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unspecified Adult Solid Tumor, Protocol Specific

Intervention

• Drug: oxaliplatin
  Given IV
  Other Names:

  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
• Drug: bortezomib
  Given IV
  Other Names:

  • LDP 341
  • MLN341
  • VELCADE
• Other: laboratory biomarker analysis
  Correlative studies
• Other: pharmacological study
  Correlative studies
  Other Name: pharmacological studies

Study Arms

Experimental: Treatment (oxaliplatin, bortezomib)

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 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.

Interventions:

• Drug: oxaliplatin
• Drug: bortezomib
• Other: laboratory biomarker analysis
• Other: pharmacological study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 8, 2006): 30
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00066625
• Other Study ID Numbers: NCI-2012-02552; NYU 02-12; N01CM62204 ( U.S. NIH Grant/Contract ); CDR0000316444 ( Registry Identifier: PDQ (Physician Data Query) )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Cancer Institute (NCI)
• Study Sponsor: National Cancer Institute (NCI)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Howard Hochster; Montefiore Medical Center

• PRS Account: National Cancer Institute (NCI)
• Verification Date: January 2013