VX-853 in Treating Patients With Solid Tumors Who Are Receiving Liposomal Doxorubicin

A Phase I/II Study of the Pharmacokinetics, Tolerability and Safety of Administration of VX-853 to Patients Receiving Single Agent Therapy With Doxorubicin HCI

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of VX-853 in treating patients who have solid tumors who are receiving liposomal doxorubicin.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: VX-853

Detailed Description

OBJECTIVES: I. Determine the safety and tolerability of VX-853 in combination with doxorubicin HCl liposome in patients with relapsed or incurable solid tumors. II. Obtain pharmacokinetic profiles for various dosages of VX-853 administered in combination with doxorubicin HCl liposome. III. Achieve whole blood concentrations of VX-853 in the predicted therapeutically effective range and characterize the pharmacokinetics at these doses. IV. Document antitumor effects of VX-853 in combination with doxorubicin HCl liposome in these patients.

OUTLINE: This is a dose escalation study of VX-853. Patients receive VX-853 orally every 8 hours on days 1-3 and doxorubicin HCL liposome IV over approximately 15 minutes beginning 26 hours after starting VX-853. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of VX-853 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose limiting toxicity.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within approximately 18 months.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Vincent T. Lombardi Cancer Research Center, Georgetown 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

DISEASE CHARACTERISTICS: Histologically proven relapsed or incurable solid tumors No primary or metastatic CNS disease

PATIENT CHARACTERISTICS: See General Eligibility Criteria

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 weeks since prior cytotoxic chemotherapy (6 weeks since prior mitomycin or nitrosourea) Prior doxorubicin HCl allowed (no extensive therapy) Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Prior surgery allowed Other: Recovered from toxic effects of prior therapy At least 4 weeks since prior investigational or approved clinical trial agents No concurrent cimetidine, phenothiazines, phenytoin, calcium channel blockers, or cyclosporine or other P-glycoprotein inhibitors --Patients Characteristics-- Age: 18 and over Performance Status: Karnofsky 70-100% Life Expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Hemoglobin at least 9.0 g/dL Platelet count at least 100,000/mm3 Hepatic: AST and/or ALT no greater than 2 times upper limit of normal Bilirubin normal Renal: Creatinine normal Creatinine clearance at least 60 mL/min Cardiovascular: No clinically significant EKG abnormalities No atrial or ventricular arrhythmias requiring medication No ischemic event within 6 months of study Cardiac ejection fraction at least 50% by MUGA scan Other: Not pregnant or nursing Fertile patients must use effective contraception No prior or concurrent seizure disorders No prior or concurrent clinically significant medical illness No known hypersensitivity to doxorubicin HCl or other study medications No other active malignancies except curatively treated carcinoma in situ of the cervix or basal cell skin cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Michael J. Hawkins, MD, Lombardi Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 1996
• Primary Completion (ACTUAL): January 1, 2001
• Study Completion (ACTUAL): January 1, 2001

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: May 24, 2004
• First Posted (ESTIMATE): May 25, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): March 24, 2011
• Last Update Submitted That Met QC Criteria: March 22, 2011
• Last Verified: January 1, 2001

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CDR0000065641; P30CA051008 (U.S. NIH Grant/Contract); GUMC-96007; VX-95-853-001; VX-GUMC-96007; NCI-V97-1275