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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00003207
Other study ID # CDR0000066062
Secondary ID WU-106NCI-T97-00
Status Completed
Phase Phase 1
First received November 1, 1999
Last updated April 11, 2013
Start date March 1998
Est. completion date July 2002

Study information

Verified date April 2013
Source Washington University School of Medicine
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Adminstration
Study type Interventional

Clinical Trial 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 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.


Recruitment information / eligibility

Status Completed
Enrollment 14
Est. completion date July 2002
Est. primary completion date July 2002
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
pegylated liposomal doxorubicin hydrochloride

PSC 833


Locations

Country Name City State
United States Washington University School of Medicine Saint Louis Missouri

Sponsors (2)

Lead Sponsor Collaborator
Washington University School of Medicine National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Yes
Primary Maximum tolerated dose of Doxil in combination with PSC 833 Yes
Primary Dose limiting toxicity of Doxil in combination with PSC 833 Yes
Secondary Effects of PSC 833 on Doxil pharmacokinetics No
Secondary Confirm the MDR expression with immunohistochemistry and functionally, with 99MTc-sestamibi No
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