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Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00182767
First received: September 15, 2005
Last updated: February 11, 2016
Last verified: February 2014

September 15, 2005
February 11, 2016
January 2006
April 2012   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: Yes ]
    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
  • 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). ] [ Designated as safety issue: Yes ]
    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
Not Provided
Complete list of historical versions of study NCT00182767 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • Progression-free Survival [ Time Frame: The time from start of treatment to time of progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    We will summarize progression-free survival by Kaplan-Meier survival analysis.
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Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer
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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Fallopian Tube Cancer
  • Female Reproductive Cancer
  • Recurrent Breast Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Stage III Ovarian Epithelial Cancer
  • Stage IV Breast Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Drug: ixabepilone
    Given IV
    Other Names:
    • BMS-247550
    • epothilone B lactam
    • Ixempra
  • Drug: pegylated liposomal doxorubicin hydrochloride
    Given IV
    Other Names:
    • CAELYX
    • Dox-SL
    • DOXIL
    • doxorubicin hydrochloride liposome
    • LipoDox
Experimental: Treatment (ixabepilone and doxorubicin)
Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1.
Interventions:
  • Drug: ixabepilone
  • Drug: pegylated liposomal doxorubicin hydrochloride
Chuang E, Wiener N, Christos P, Kessler R, Cobham M, Donovan D, Goldberg GL, Caputo T, Doyle A, Vahdat L, Sparano JA. Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary. Ann Oncol. 2010 Oct;21(10):2075-80. doi: 10.1093/annonc/mdq080. Epub 2010 Mar 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
45
May 2014
April 2012   (final data collection date for primary outcome measure)

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.
Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00182767
NCI-2009-00140, NCI-2009-00140, 0504007857, 7229, N01CM62204, P30CA013330
Yes
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Ellen Chuang Montefiore Medical Center - Moses Campus
National Cancer Institute (NCI)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP