Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Ixabepilone and Liposomal Doxorubicin in Treating Women With Advanced Ovarian Epithelial, Peritoneal Cavity, or Fallopian Tube Cancer or Metastatic Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 18 and over NCI AECM-0504007857 NCI-7229, 7229, NCT00182767

Objectives

1. Determine the maximum tolerated dose and recommended phase II dose of ixabepilone when combined with pegylated doxorubicin HCl liposome in women with previously treated advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer or metastatic breast cancer.
2. Determine the safety profile of this regimen in these patients.
3. Determine the clinical efficacy of this regimen in patients with platinum- and taxane-resistant advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed diagnosis of 1 of the following:
  • Advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer (phase I [closed to accrual as of 12/6/07] and II)
  • Metastatic breast cancer (phase I only [closed to accrual as of 12/6/07])



• 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
  • 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)



• 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
    • Platinum-refractory or -sensitive disease (phase I [closed to accrual as of 12/6/07])
    • Platinum- and taxane-resistant disease, defined as a disease-free interval of < 6 months after completion of platinum- and taxane-based chemotherapy OR disease progression during the regimen (phase II)
  • Previously treated with ≥ 2 prior regimens for metastatic breast cancer, including 1 taxane-based regimen in the adjuvant or metastatic setting (phase I [closed to accrual as of 12/6/07])



• 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
  • Clinical symptoms of brain metastasis



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• 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
• No prior doxorubicin HCl liposome

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• At least 3 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• Recovered for more than 4 weeks from all adverse events related to prior agents
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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

Expected Enrollment

A total of 20-50 patients (3-18 for the phase I portion and 17-32 for the phase II portion) will be accrued for this study.

Outcomes

Safety

Response rate
Disease-free survival

Outline

This is a phase I (closed to accrual as of 12/6/07), multicenter, open-label, dose-escalation study of ixabepilone followed by a phase II study.

• Phase I (closed to accrual as of 12/6/07): Patients receive ixabepilone IV over 3 hours and pegylated doxorubicin HCl liposome IV over 30-60 minutes on day 1. Courses repeat every 21-28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 4 additional courses beyond CR. Patients receive a maximum cumulative doxorubicin dose of 500 mg/m² (including prior doxorubicin and pegylated doxorubicin HCl liposome). Patients with responding disease may continue to receive ixabepilone alone at the discretion of the treating physician.

  Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 6 patients experience dose-limiting toxicity.




• Phase II: Patients receive ixabepilone (at the MTD determined in phase I) and pegylated doxorubicin HCl liposome as in phase I (closed to accrual as of 12/6/07).

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

Chuang E, Vahdat L, Caputo T, et al.: Phase I clinical trial of ixabepilone and pegylated liposomal doxorubicin in patients with advanced breast or ovarian cancers: New York Cancer Consortium trial P7229. [Abstract] J Clin Oncol 25 (Suppl 18): A-2570, 2007.

Trial Contact Information

Trial Lead Organizations

Albert Einstein Cancer Center at Albert Einstein College of Medicine

Ellen Chuang, MD, Principal investigator		Ph: 212-821-0654 Email: elc2007@med.cornell.edu

U.S.A.
Connecticut
	Farmington
	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
		Carolyn Runowicz, MD	Ph:  860-679-4535
New York
	New York
	New York Weill Cornell Cancer Center at Cornell University
		Clinical Trials Office - New York Weill Cornell Cancer Center at Cornell University	Ph:  212-746-1848
	NYU Cancer Institute at New York University Medical Center
		Franco Muggia, MD	Ph:  212-263-6485
			Email: muggif01@gcrc.med.nyu.edu

Registry Information
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
Trial Start Date		2005-10-20
Trial Completion Date		2008-05-07 (estimated)
Registered in ClinicalTrials.gov		NCT00182767
Date Submitted to PDQ		2005-07-18
Information Last Verified		2006-11-16
NCI Grant/Contract Number		CM17103