Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

February 11, 2016 updated by: National Cancer Institute (NCI)

A Phase I/II Study of BMS-247550 and Pegylated Liposomal Doxorubicin (Doxil®) in Patients With Advanced Epithelial Ovarian Cancer or Primary Peritoneal Cancer Who Have Been Previously Treated With a Platinum and a Taxane

This trial is studying the side effects and best dose of ixabepilone when given together with pegylated liposomal doxorubicin hydrochloride and to see how well they work in treating women with advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer or metastatic breast cancer. Drugs used in chemotherapy, such as ixabepilone and pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and recommended phase II dose of ixabepilone when combined with pegylated doxorubicin hydrochloride (HCl) liposome (pegylated liposomal doxorubicin hydrochloride) in women with previously treated advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer or metastatic breast cancer.

II. To determine the safety profile of this regimen in these patients. III. To determine the clinical efficacy of this regimen in patients with platinum- and taxane-resistant advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer.

OUTLINE: This is a phase I, multicenter, open-label, dose-escalation study of ixabepilone followed by a phase II study.

Patients receive ixabepilone intravenously (IV) over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. Courses repeat every 21-28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for up to 2 years.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2
  • 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
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
    • New York
      • Albany, New York, United States, 12208
        • Women's Cancer Care Associates LLC
      • Bronx, New York, United States, 10461
        • Albert Einstein College Of Medicine
      • Bronx, New York, United States, 10467-2490
        • Montefiore Medical Center - Moses Campus
      • New York, New York, United States, 10065
        • Weill Medical College of Cornell University

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of 1 of the following: advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer (phase I and II) or metastatic breast cancer (phase I only).
  • Platinum- and taxane-resistant disease, defined as a disease-free interval of < 6 months after completion of platinum- and taxane-based chemotherapy. Disease progression during the regimen (phase II) or previously treated with >= 2 prior regimens for metastatic breast cancer, including 1 taxane-based regimen in the adjuvant or metastatic setting (phase I).
  • Meets 1 of the following criteria: Previously treated with a standard course of taxane- and platinum-based chemotherapy for ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer, that is platinum-refractory or -sensitive disease (phase I );
  • Measurable or evaluable disease, meeting 1 of the following criteria: unidimensionally measurable lesion, known disease and CA 125 > 50 U/mL on 2 occasions >= 1 week apart or known disease and CA 27-29, CA 15-3, or CA 125 > 50 U/mL on 2 occasions >= 1 week apart (for breast cancer patients)
  • ECOG 0-2 or Karnofsky 60-100%
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered.
  • At least 1 week since prior chemotherapy if given on a daily or weekly schedule and recovered.
  • At least 3 weeks since prior radiotherapy and recovered.
  • Recovered for more than 4 weeks from all adverse events related to prior agents.
  • Normal organ function including:
  • Normal bilirubin
  • WBC >= 3,000/mm3
  • Absolute neutrophil count >= 1,500/mm3
  • Platelet count >= 100,000/mm3
  • AST and ALT =< 2.5 times upper limit of normal (ULN)
  • Creatinine =< 1.5 times ULN or Creatinine clearance ≥ 60 mL/min

Exclusion criteria:

  • No other concurrent investigational agents.
  • No concurrent combination antiretroviral therapy for HIV-positive patients.
  • No other concurrent anticancer therapy.
  • Has received a previous chemotherapy regimen for this cancer that included drugs such as docetaxel or paclitaxel.
  • Life expectancy of more than 3 months
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to Cremophor® or study drugs
  • No neuropathy >= grade 2
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance.
  • No other uncontrolled illness.
  • No active brain metastases, including any of the following: evidence of cerebral edema by CT scan or MRI, evidence of disease progression on prior imaging studies, requirement for steroids or clinical symptoms of brain metastasis.

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: Treatment (ixabepilone and doxorubicin)
Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1.
Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • doxorubicin hydrochloride liposome
  • LipoDox
  • Dox-SL
  • CAELYX
  • DOXIL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I)
Time Frame: 28 days
Dose-Limiting Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification and usually encompasses all grade 3 or higher toxicities
28 days
Maximum Tolerated Dose
Time Frame: Once 2 DLT events occur in patients during the first 28 days of treatment (cycle 1), the preceding dose will be designated the maximum tolerated dose (MTD).
The phase I component of the study included 30 patients with breast and ovarian cancer. A protocol amendment was made during phase I trial from a treatment regimen of Schedule A (ixabepilone every 3-4 weeks) to Schedule B (ixabepilone every week). The maximum tolerated dose was determined to be the preceding dose of any dose that resulted in 2 DLT events. Schedule B was carried forward to the phase II trial. The Maximum Tolerated Dose for Schedule B is reported. Please see (Chuang et al., 2010) for additional details
Once 2 DLT events occur in patients during the first 28 days of treatment (cycle 1), the preceding dose will be designated the maximum tolerated dose (MTD).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Patients Responding to Therapy (Complete Response [CR], Partial Response [PR], or Stable Disease [SD]), Assessed According to Response Evaluation Criteria in Solid Tumors (RECIST) and Cancer Antigen-125 (CA-125) Response Criteria (Phase II)
Time Frame: Up to 2 years
Up to 2 years
Progression-free Survival
Time Frame: The time from start of treatment to time of progression or death, assessed up to 2 years
We will summarize progression-free survival by Kaplan-Meier survival analysis.
The time from start of treatment to time of progression or death, assessed up to 2 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ellen Chuang, Montefiore Medical Center - Moses Campus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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, 2006

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

September 15, 2005

First Submitted That Met QC Criteria

September 15, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Estimate)

March 10, 2016

Last Update Submitted That Met QC Criteria

February 11, 2016

Last Verified

February 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00140 (Other Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA013330 (U.S. NIH Grant/Contract)
  • N01CM62204 (U.S. NIH Grant/Contract)
  • 0504007857 (Other Identifier: Montefiore Medical Center - Moses Campus)
  • 7229 (Other Identifier: CTEP)

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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