Clinical trial NCT00182767: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-09-16
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I)
timeFrame: 28 days
measure: Maximum Tolerated Dose
timeFrame: 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 outcomes:
measure: 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)
timeFrame: Up to 2 years
measure: Progression-free Survival
timeFrame: The time from start of treatment to time of progression or death, assessed up to 2 years
Other outcomes:
Locations:
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Albany
country: United States
facility: Women's Cancer Care Associates LLC
state: New York
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
Study officials:
affiliation: Montefiore Medical Center - Moses Campus
name: Ellen Chuang
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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):2075-2080. doi: 10.1093/annonc/mdq080. Epub 2010 Mar 31.