Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

Brief Title

Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

Official Title

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

Brief Summary

      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.

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 Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I)

Secondary Outcome

 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)

Condition

Fallopian Tube Cancer

Intervention

ixabepilone

Study Arms / Comparison Groups

 Treatment (ixabepilone and doxorubicin)

Description:  Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

January 2006

Completion Date

May 2014

Primary Completion Date

April 2012

Eligibility Criteria

        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.

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Ellen Chuang, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT00182767

Organization ID

NCI-2009-00140

Secondary IDs

NCI-2009-00140

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

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

Verification Date

February 2014