Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer

Tracking Information
First Submitted Date ICMJE	August 6, 2003
First Posted Date ICMJE	August 7, 2003
Last Update Posted Date	February 1, 2013
Study Start Date ICMJE	July 2003
Actual Primary Completion Date	April 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (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 ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00066625 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (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 ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer
Official Title ICMJE	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 ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Unspecified Adult Solid Tumor, Protocol Specific
Intervention ICMJE	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
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: November 8, 2006)	30
Original Enrollment ICMJE	Not Provided
Study Completion Date	Not Provided
Actual Primary Completion Date	April 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00066625
Other Study ID Numbers ICMJE	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 ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Howard Hochster Montefiore Medical Center
PRS Account	National Cancer Institute (NCI)
Verification Date	January 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP