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Pharmacokinetic Study of Avastin and Doxil in Ovarian Cancer

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Doxil
Bevacizumab (Avastin)
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring refractory, avastin, doxil, relapsed, ovarian cancer, platinum-resistant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Univ. of New Mexico cancer research and treatment center
  • Bellevue Hospital
  • NYU Cancer Center
  • NYU medical center (Tisch Hospital)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Avastin-Doxil

Arm Description

Outcomes

Primary Outcome Measures

change in peak plasma concentration of Doxil without and with Avastin
In cycle 1, patients were treated only with Doxil; in cycle 2, patients were treated with Doxil and Avastin.

Secondary Outcome Measures

Full Information

First Posted
February 18, 2009
Last Updated
September 26, 2019
Sponsor
NYU Langone Health
Collaborators
Genentech, Inc., University of New Mexico Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00846612
Brief Title
Pharmacokinetic Study of Avastin and Doxil in Ovarian Cancer
Official Title
Phase II and Pharmacokinetic Study of Avastin and Doxil in the Treatment of Platinum-resistant or Refractory Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
Genentech, Inc., University of New Mexico Cancer Center

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
refractory, avastin, doxil, relapsed, ovarian cancer, platinum-resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Avastin-Doxil
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Doxil
Other Intervention Name(s)
pegylated doxorubicin liposome
Intervention Description
1 cycle: 3 weeks; 30 mg/m^2, IV, every cycle
Intervention Type
Drug
Intervention Name(s)
Bevacizumab (Avastin)
Other Intervention Name(s)
Avastin
Intervention Description
1 cycle: every 3 weeks; 15 mg/kg, IV, beginning on cycle 2 and every cycle 20-24 hours following Doxil administration
Primary Outcome Measure Information:
Title
change in peak plasma concentration of Doxil without and with Avastin
Description
In cycle 1, patients were treated only with Doxil; in cycle 2, patients were treated with Doxil and Avastin.
Time Frame
1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Franco Muggia, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Univ. of New Mexico cancer research and treatment center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Bellevue Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU medical center (Tisch Hospital)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States

12. IPD Sharing Statement

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Pharmacokinetic Study of Avastin and Doxil in Ovarian Cancer

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