Rebeccamycin Analog and Oxaliplatin in Treating Patients With Refractory Solid Tumors

A Phase I Study of XL119 (Rebeccamycin Analogue) in Combination With Oxaliplatin in Patients With Refractory Solid Tumors

This phase I trial is studying the side effects and best dose of rebeccamycin analog and oxaliplatin in treating patients with refractory solid tumors. Drugs used in chemotherapy, such as rebeccamycin analog and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: oxaliplatin; Other: pharmacological study; Drug: becatecarin

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of XL119 given in conjunction with oxaliplatin.

II.To determine the dose limiting toxicities of this combination. III. To determine the pharmacokinetics of these 2 agents when given in combination.

OUTLINE: This is a dose-escalation study.

Patients receive rebeccamycin analogue IV over 1 hour on days 1-5 and oxaliplatin IV over 2 hours on day 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Patients are followed annually for survival.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have a histologically confirmed solid tumor that is not amenable to conventional surgical, radiation therapy or chemotherapy treatment programs
• Prior chemotherapy and/or radiation are allowed; at least 4 weeks must have elapsed since prior large-field radiation therapy; patients must have been off previous anti-cancer therapy for at least 3 weeks (6 weeks for mitomycin-C and nitrosoureas); and recovered from all treatment related toxicity
• ECOG performance status =< 2 (Karnofsky >60%)
• Life expectancy of at least 12 weeks
• Absolute neutrophil count >= 1,500/ul
• Platelets >= 100,000/ul
• Hemoglobin >= 9.0 g/dl
• Total bilirubin =< 1.5 mg/dl
• AST(SGOT) < 2.5 X institutional upper limit of normal
• Creatinine < 1.5 mg/dl OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• All patients should have a central line placed for XL119 administration

Exclusion Criteria:

• Patients may not be receiving any other investigational agents or have received other investigational agents for at least 4 weeks
• Patients with known brain metastases should be excluded from this clinical trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and lactating women are excluded from this study
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
• NYHA classification III or IV heart disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (becatacarin, oxaliplatin); Patients receive rebeccamycin analogue IV over 1 hour on days 1-5 and oxaliplatin IV over 2 hours on day 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of rebeccamycin analogue and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Drug: oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: becatecarin; Given IV; Other Names: BMS-181176; rebeccamycin analogue; rebeccamycin analogue, tartrate salt; XL119

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose defined as the highest dose tested in which none or only one patient experienced dose limiting toxicities as measured by Common Toxicity Criteria	21 days

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Afshin Dowlati, Case Western Reserve University

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: July 8, 2004
• First Submitted That Met QC Criteria: July 9, 2004
• First Posted (Estimate): July 12, 2004

Study Record Updates

• Last Update Posted (Estimate): January 10, 2013
• Last Update Submitted That Met QC Criteria: January 9, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: NCI-2012-03118; U01CA062502 (U.S. NIH Grant/Contract); CASE 4Y03