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
Conditions
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.
Interventions
DRUGixabepilone
Given IV
DRUGpegylated liposomal doxorubicin hydrochloride
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) | 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 |
| Maximum Tolerated Dose | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 2 years | — |
| Progression-free Survival | 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. |
Countries
United States
Participant flow
Recruitment details
A total of 45 patients were enrolled and treated between January 2006 and May 2011
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Ixabepilone and Doxorubicin) Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes.
ixabepilone: Given IV
pegylated liposomal doxorubicin hydrochloride: Given IV | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | Treatment (Ixabepilone and Doxorubicin) |
|---|---|
| Age, Continuous | 59 years |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 3 / 3 | 24 / 24 |
| serious Total, serious adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 3 / 3 | 24 / 24 |
Outcome results
Primary
Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I)
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
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1 | Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) | 1 participants |
| Ixabepilone 32mg/m2 and Doxorubicin 30mg/m2: Level 2 | Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) | 1 participants |
| Ixabepilone 40mg/m2 and Doxorubicin 30mg/m2: Level 3 | Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) | 2 participants |
| Ixabepilone 13mg/m2 and Doxorubicin 30mg/m2: Level 4 | Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) | 0 participants |
| Ixabepilone 16mg/m2 and Doxorubicin 30mg/m2: Level 5 | Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) | 0 participants |
Primary
Maximum Tolerated Dose
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
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).
Population: The phase I component of the study included 30 patients with breast and ovarian cancer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1 | Maximum Tolerated Dose | 16 mg/m2 |
Secondary
Progression-free Survival
We will summarize progression-free survival by Kaplan-Meier survival analysis.
Time frame: The time from start of treatment to time of progression or death, assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1 | Progression-free Survival | 4.1 months |
Secondary
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1 | 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) | Ovarian Cancer | 20 participants |
| Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1 | 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) | Breast Cancer | 7 participants |