Skip to main content
OpenTrials
Completed

NCT Number: NCT00003207

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

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 also increase. Doxil is chosen since recent studies have shown that it is superior to combination chemotherapy with ABV or BV. Doxil is also known to be active in other malignancies such as breast and ovarian cancer (34,35). PSC 833 is chosen since it has been found to reverse P-gp in vitro and in vivo, is non-immunosuppressive, and has been shown in recent Phase 1 studies to be well tolerated.

There are yet no human studies reported on Doxil pharmacokinetics when combined with MDR modulators. Preclinical data shows that pharmacokinetics of Doxil, unlike free doxorubicin, is minimally affected by the addition of PSC 833 (36). Enhanced tumor toxicity was observed when PSC 833 was combined with Doxil. Since doxorubicin, the active agent in Doxil, is metabolized by the same cytochrome P450, interactions between these 2 agents may have very significant clinical implications. The purpose of this study is to assess the toxicity and determine the maximum tolerated dose of Doxil when combined with PSC 833 in the treatment of AIDS-KS and other advanced malignancies.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Sarcoma AIDS-related Kaposi sarcoma DNA Virus Infections Herpesviridae Infections Infections Neoplasms Neoplasms by Histologic Type Neoplasms, Connective and Soft Tissue Neoplasms, Vascular Tissue Sarcoma, Kaposi Unspecified Adult Solid Tumor, Protocol Specific Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically documented malignancy refractory to standard treatment or for which no standard treatment exists, or biopsy proven Kaposi's sarcoma with mucocutaneous lesions numbering 10 or more or a documented visceral KS lesion with at least 2 assessable cutaneous lesions.
  • A life expectancy of >4 months.
  • Patients with prior chemotherapy and Doxil exposure are eligible
  • Age >=18
  • Karnofsky score of >=70%
  • Hemoglobin >=8 g/dl, neutrophil count >=1000 cells/ul and platelet count of >=75,000 cells/ul.
  • Creatinine clearance of .=50 ml/min or creatinine of <=2.0mg/dl, SGOT <=2X the institutional normal and bilirubin <1.5X institutional normal
  • Written informed consent has been obtained from the patient.

Exclusion criteria

  • Pregnant or breast feeding patients as radioactive tracer material and chemotherapy will be used in this protocol.
  • Active opportunistic infections requiring antibiotic treatment.
  • Treatment with radiation or electron beam therapy, interferon or cytotoxic therapy within the preceding 4 weeks.
  • Clinically significant history of congestive heart failure.
  • Patients who have moderate to severe sensory and motor peripheral neuropathy.
  • Any patient currently receiving treatment with any of the following agents which cannot be discontinued at a specified time relative to PSC 833 administration. All of these drugs are well substantiated to interact with cyclosporin A:
  • Agents increasing serum concentrations of CsA

The following drugs must not be administered for 48 hours before PSC 833 is started, during the course of its administration, or up to 48 hours after the last dose of PSC 833 in a cycle:

Calcium channel blockers: diltiazem, nicardipine, verapamil Antifungals: fluconazole (dose <200 mg/day allowed), itraconazole, ketoconazole Antibiotics: clarithromycin, erythromycin Others: metoclopramide,bromocriptine, danazol

  • Agents decreasing serum concentrations of CsA

The following drugs must not be administered in the 14 days before PSC 833 is started or during the course of its administration. They may be restarted immediately after the last dose of PSC 833:

Antibiotics: nafcillin, rifampin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Others: octreotide, ticlopidine

  • Hypersensitivity to Doxil or cyclosporin A
  • Any patient, who, in the judgment of the investigator, may not be able to complete this study.

Treatment and study plan

Pegylated Liposomal Doxorubicin Hydrochloride

Drug

Other names: DOXIL

PSC 833

Drug

Other names: valspodar

Primary outcomes

  1. 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

  2. Maximum tolerated dose of Doxil in combination with PSC 833

  3. Dose limiting toxicity of Doxil in combination with PSC 833

Secondary outcomes

  1. Effects of PSC 833 on Doxil pharmacokinetics

  2. Confirm the MDR expression with immunohistochemistry and functionally, with 99MTc-sestamibi

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

Phase I Study on Doxil and SDZ PSC 833 in the Treatment of AIDS-Associated Kaposi's Sarcoma and Other Advanced Malignancies

Important dates

Study start
1998
Primary completion
2002
Study completion
2002
First posted
Feb 16, 2004
Registry last updated
Apr 12, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.