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SarcomaPhase 1NCT00003207

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

A Phase 1 study testing pegylated liposomal doxorubicin hydrochloride and PSC 833 in people with Sarcoma and Unspecified Adult Solid Tumor, Protocol Specific, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pegylated liposomal doxorubicin hydrochloride and PSC 833
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
Mar 1998to Jul 2002
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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:
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Being tested
pegylated liposomal doxorubicin hydrochloride, PSC 833
Keywords
unspecified adult solid tumor, protocol specific, AIDS-related Kaposi sarcoma, recurrent Kaposi sarcoma
Medical subject headings
Sarcoma, AIDS-related Kaposi sarcoma, Sarcoma, Kaposi

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pegylated liposomal doxorubicin hydrochlorideDrug

    Also called DOXIL

  • PSC 833Drug

    Also called valspodar

Study groups in NCT00003207
Study groupRoleWhat they receive
Phase 1 (Doxil & PSC 833)ExperimentalPatients 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.
Receives: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: PSC 833

What is being measured

The primary outcome is the main question the study is designed to answer.

  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 (2)

  1. Effects of PSC 833 on Doxil pharmacokinetics

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2004 (estimated)
  2. Study startMar 1998
  3. Primary completionJul 2002
  4. Study completionJul 2002

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003207
Sponsor's protocol ID
CDR0000066062
Other IDs
WU-106, NCI-T97-0073
Status last verified
Apr 2013
First submitted
1 Nov 1999
Last updated
12 Apr 2013
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing pegylated liposomal doxorubicin hydrochloride and PSC 833 in people with Sarcoma and Unspecified Adult Solid Tumor, Protocol Specific, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety profile and tolerability of Doxil in combination with PSC 833. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003207.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2013.

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