Liposomal Doxorubicin and PSC 833 in Treating Patients With AIDS-Related Kaposi's Sarcoma or Other Advanced Cancers

Registration Number
NCT00003207
Lead Sponsor
Washington University School of Medicine
Brief Summary

The rationale for conducting this study lies in the premise that if indeed the reason for a limited response of Kaposi's sarcoma lesions and other advanced malignancies to chemotherapy is attributable to a high expression of P-glycoprotein, then, by inhibiting this pump, tumor kill would be enhanced and response rates as well as duration of responses would a...

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
14
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Phase 1 (Doxil & PSC 833)pegylated liposomal doxorubicin hydrochloridePatients will receive Doxil at the standard dose of 20 mg/m2 IV for the 1st cycle. On the 2nd cycle of Doxil, the first patient will receive Doxil at 40% of standard dose or 8 mg/m2 (dose level 1) IV over one hr. 15 mn after the 2nd and subsequent cycles of Doxil, PSC 833 will be given at 2 mg/kg for 2 hrs. Simultaneously, a 72 hour CIVI of PSC 833 will be started with the loading dose. If no DLT occurs, then a double dose escalation of Doxil (dose levels 3, 5, 7 ) will be given to the same patient in the subsequent cycles until DLT occurs. On the 2nd cycle, Doxil will be given at the next dose level above the starting dose tolerated by the first patient. If no DLT occurs, a double dose escalation will also be done for the subsequent cycles (dose levels 5, 7, 9). The single-patient-cohort will terminate when a patient experiences DLT or when two episodes of grade 2 toxicity occur. At that point patients will be enrolled into cohorts of 3 patients to determine the MTD.
Phase 1 (Doxil & PSC 833)PSC 833Patients will receive Doxil at the standard dose of 20 mg/m2 IV for the 1st cycle. On the 2nd cycle of Doxil, the first patient will receive Doxil at 40% of standard dose or 8 mg/m2 (dose level 1) IV over one hr. 15 mn after the 2nd and subsequent cycles of Doxil, PSC 833 will be given at 2 mg/kg for 2 hrs. Simultaneously, a 72 hour CIVI of PSC 833 will be started with the loading dose. If no DLT occurs, then a double dose escalation of Doxil (dose levels 3, 5, 7 ) will be given to the same patient in the subsequent cycles until DLT occurs. On the 2nd cycle, Doxil will be given at the next dose level above the starting dose tolerated by the first patient. If no DLT occurs, a double dose escalation will also be done for the subsequent cycles (dose levels 5, 7, 9). The single-patient-cohort will terminate when a patient experiences DLT or when two episodes of grade 2 toxicity occur. At that point patients will be enrolled into cohorts of 3 patients to determine the MTD.
Primary Outcome Measures
NameTimeMethod
Safety profile and tolerability of Doxil in combination with PSC 833

Each cycle is 2 weeks long and can continue until disease progression, toxicity, or patient decision

Maximum tolerated dose of Doxil in combination with PSC 833
Dose limiting toxicity of Doxil in combination with PSC 833
Secondary Outcome Measures
NameTimeMethod
Effects of PSC 833 on Doxil pharmacokinetics
Confirm the MDR expression with immunohistochemistry and functionally, with 99MTc-sestamibi

Trial Locations

Locations (1)

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

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