Pharmacokinetic Study of Avastin and Doxil in Ovarian Cancer

September 26, 2019 updated by: NYU Langone Health

Phase II and Pharmacokinetic Study of Avastin and Doxil in the Treatment of Platinum-resistant or Refractory Ovarian Cancer

This study is to study pharmacokinetics of Doxil using Doxil and Avastin on ovarian cancer patients who are resistant to or have relapsed from platinum-based therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study registration at clinicaltrials.gov is divided into 2 records. This record (NCT00846612) is for pharmacokinetics of Doxil. Another record (NCT00945139) describes the efficacy and safety of the combination treatment.

Treatment upon diagnosis of epithelial ovarian cancer (EOC) consists of surgery to achieve maximal tumor debulking followed by platinum-based chemotherapy (carboplatin + paclitaxel). Recently, optimally (e.g., < 1 cm residual disease) debulked patients appear to benefit from regimens that include intraperitoneal administration of cisplatin. While complete response (CR) is frequently achieved, by two years 50% of the patients show signs of recurrence.

When EOC presenting at an advanced stage recurs, even after a CR had been achieved, it can no longer be totally eradicated. Nevertheless, a number of drugs lead to objective responses, patients benefit with a prolongation of survival. Anti-tumor activity of Doxil against ovarian cancer was noted in a phase I study, and this was followed by a phase II study that demonstrated activity in platinum and paclitaxel refractory disease. In the expanded phase II experience at the University of Southern California, responses to Doxil occurred preferably in disease that was not bulky and after fewer prior treatments. Typically, several cycles were required for maximum response, and some patients had prolonged stable disease. Subsequently, the study of Gordon et al established the preferred role of this drug formulation in the 2nd line-setting. It is logical, therefore, to build on this agent in trying to improve the outcome of patients with recurrent ovarian cancer, and in particular, to consider a combination with Avastin, since Avastin has shown agent activity in retrospective data and recent studies in EOC.

A combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible via increased half-life (if liposomal egress is diminished) and decreased tumoral interstitial pressure, 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Pharmacokinetic issues will be addressed in selected patients, by comparing cycle 1 (without Avastin) with cycle 2 (with Avastin).

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Univ. of New Mexico cancer research and treatment center
    • New York
      • New York, New York, United States, 10016
        • Bellevue Hospital
      • New York, New York, United States, 10016
        • NYU Cancer Center
      • New York, New York, United States, 10016
        • NYU medical center (Tisch Hospital)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patients must be platinum resistant
  • No prior anthracycline use
  • PS ≤ 2
  • Lab values within certain limits (ANC > 1000, platelets > 100,000; ALT, AST 2x ULN, creatinine < 2.0);
  • No more than 3 prior chemotherapy regimens, only 2 of which can have included platinum-containing regimens.
  • Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

  • Disease-Specific Exclusions:

    • Evidence of complete or partial bowel obstruction
    • Need for IV hydration or TPN
    • > 2 prior abdominal surgeries
    • History of gastrointestinal perforation
    • Gastrointestinal perforation due to any other cause within the last 6 months

  • General Medical Exclusions:

    • Inability to comply with study and/or follow-up procedures
    • Life expectancy of less than 12 weeks
    • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study

  • Avastin-Specific Exclusions:

    • Inadequately controlled hypertension (defined as systolic blood pressure greater than 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
    • Any prior history of hypertensive crisis or hypertensive encephalopathy
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E of the protocol)
    • History of myocardial infarction or unstable angina within 6 months prior to study enrollment
    • History of stroke or transient ischemic attack within 6 months prior to study enrollment
    • Known CNS disease
    • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
    • Symptomatic peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
    • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
    • History of abdominal fistula, or intra-abdominal abscess within 6 months prior to study enrollment
    • Serious, non-healing wound, ulcer, or bone fracture

    • Proteinuria at screening as demonstrated by either

      • Urine protein:creatinine (UPC) ratio no less than 1.0 at screening OR
      • Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
    • Known hypersensitivity to any component of Avastin
    • Pregnant (positive pregnancy test) or lactating. No effective means of contraception (men and women) in subjects of child-bearing potential

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Avastin-Doxil
Drug: Doxil
1 cycle: 3 weeks; 30 mg/m^2, IV, every cycle
Other Names:
  • pegylated doxorubicin liposome
Drug: Bevacizumab (Avastin)
1 cycle: every 3 weeks; 15 mg/kg, IV, beginning on cycle 2 and every cycle 20-24 hours following Doxil administration
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change in peak plasma concentration of Doxil without and with Avastin
Time Frame: 1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2
In cycle 1, patients were treated only with Doxil; in cycle 2, patients were treated with Doxil and Avastin.
1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

Genentech, Inc.
University of New Mexico Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

February 18, 2009

First Submitted That Met QC Criteria

February 18, 2009

First Posted (Estimate)

February 19, 2009

Study Record Updates

Last Update Posted (Actual)

September 30, 2019

Last Update Submitted That Met QC Criteria

September 26, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-948
  • Genentech AVF3910s (Other Identifier: Genentech)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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