Epothilone B in Treating Patients With CNS Metastases From Breast Cancer

Phase II Trial of Patupilone in Patients With Brain Metastases From Breast Cancer

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00450866

Enrollment

Registered

2007-03-22

Start date

2007-01-31

Completion date

2012-05-31

Last updated

2014-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer, Metastatic Cancer

Keywords

recurrent breast cancer, stage IV breast cancer, tumors metastatic to brain, leptomeningeal metastases, male breast cancer

Brief summary

RATIONALE: Drugs used in chemotherapy, such as epothilone B, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well epothilone B works in treating patients with CNS metastases from breast cancer.

Detailed description

OBJECTIVES: Primary * Determine the 3-month CNS-progression free survival of patients with CNS metastases secondary to breast cancer treated with epothilone B. Secondary * Determine the toxicity of this drug in these patients. * Determine the CNS response rate and duration of CNS response in patients treated with this drug. * Determine the systemic disease response rate and duration of systemic response in patients treated with this drug. * Determine the overall survival of patients treated with this drug. OUTLINE: This is a multicenter, open-label study. Patients receive epothilone B IV over 20 minutes on day 1. Courses repeat every 21 days in the absence of disease progression, satisfactory response, or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Interventions

BIOLOGICALepothilone B

Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed carcinoma of the breast * CNS metastases (i.e., brain parenchymal lesions and/or leptomeningeal disease), meeting 1 of the following criteria: * Recurrent or progressive CNS metastases after whole brain radiotherapy * If only evaluable site of CNS progression has been previously treated with stereotactic radiosurgery, radiation necrosis must be excluded by radiographic (e.g., positron emission tomography scan or magnetic resonance spectroscopy) or histologic assessment * Newly diagnosed, untreated, asymptomatic brain or leptomeningeal metastases * Patient must be neurologically stable, as demonstrated by a stable dose of steroids and anticonvulsants for ≥ 1 week prior to obtaining baseline gadolinium-enhanced MRI of the brain and/or ≥ 1 week prior to beginning study treatment * No CNS complications requiring urgent neurosurgical intervention (e.g., resection or shunt placement) * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Male or female * Menopausal status not specified * Karnofsky performance status 60-100% * Life expectancy ≥ 3 months * Absolute neutrophil count \> 1,500/mm\^3 * Hemoglobin \> 9.0 g/dL * Platelet count \> 100,000/mm\^3 (red blood cell transfusion and repeat evaluation allowed) * Bilirubin \< 1.5 times upper limit of normal (ULN) * AST and ALT \< 2.5 times ULN * Alkaline phosphatase \< 2.5 times ULN * Creatinine \< 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study therapy * No known hypersensitivity to epothilones * No peripheral neuropathy \> grade 1 * No unresolved diarrhea within the past 7 days * Grade 0 diarrhea required at study entry * No concurrent serious medical illness (e.g., HIV positivity or active hepatitis B or C) * No severe cardiac insufficiency (e.g., New York Heart Association class III-IV heart disease) with uncontrolled and/or unstable cardiac or coronary artery disease * No active or suspected acute or chronic uncontrolled infection, including abscess or fistulae * No other malignancy within the past 3 years except curatively treated nonmelanoma skin cancer, prostate cancer, or carcinoma in situ of the cervix * No history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits * No contraindications to MRI, including any of the following: * Pacemaker * Ferromagnetic implants * Claustrophobia * Extreme obesity PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 2 weeks since prior noncytotoxic drugs (e.g., small molecule-targeted drugs) and recovered * More than 3 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered * More than 3 weeks since prior intracranial surgery and recovered * More than 4 weeks since prior radiotherapy and recovered * More than 4 weeks since prior major surgery * More than 28 days since prior investigational compounds or drugs * No prior epothilones * No concurrent known diarrheagenic agents * No other concurrent anticancer agents, including investigational agents, biological agents, or chemotherapy * No other concurrent experimental therapies * Concurrent hormone therapy and/or trastuzumab (Herceptin®) allowed * No concurrent Coumadin® or other agents containing warfarin * Low dose Coumadin® (≤ 1 mg) for prophylactic maintenance of indwelling lines or ports allowed * No concurrent radiotherapy for central metastases (e.g., vertebral or mediastinal metastases) * Concurrent radiotherapy for local peripheral metastases not being used as marker lesions allowed * No concurrent prophylactic hematopoietic growth factors during course 1 * No concurrent herbal or nontraditional medications

Design outcomes

Primary

Measure	Time frame	Description
Central Nervous System (CNS) Progression-free Survival(PFS)	3 months after treatment	The number of patients that are documented to have progression free survival at 3 months after treatment. Progression free is define as \<25% increase in tumor area. PFS will be measured from the date of entry into the trial to the date of documented progression of brain metastases or death.

Secondary

Measure	Time frame	Description
Toxicity as Measured by NCI CTCAE v3.0	3 months after treatment	Percent of patients that experience the most common grade 3 and above toxicities possibly related to study drug - to be measured using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.
CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria	3 months after treatment	Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of \>50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a \> 25% increase in tumor area (two diameters)
Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria	3 months after treatment	Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of \>50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a \> 25% increase in tumor area (two diameters)
Overall Survival	48 months from start of study	Median time (months) that patients survived during the duration of the study.

Countries

United States

Participant flow

Recruitment details

This was a multicenter conducted at the Cleveland Clinic, University Hospitals Case Medical Center, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, and the University of Michigan.Fifty five patients were treated on this study between February 2007 and May 2010, all of whom are considered eligible.

Participants by arm

Arm	Count
Epothilone B (Groups A and B) Epothilone B : Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.	55
Total	55

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Death	1	0
Overall Study	Physician Decision	1	0
Overall Study	Withdrawal by Subject	5	2

Baseline characteristics

Characteristic	Epothilone B (Groups A and B)
Age, Continuous	50 years FULL_RANGE 8.6
Central Nervous System (CNS) metastases Group A	45 participants
Central Nervous System (CNS) metastases Group B	10 participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	4 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	48 Participants
Region of Enrollment United States	55 participants
Sex: Female, Male Female	55 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	55 / 55
serious Total, serious adverse events	18 / 55

Outcome results

Primary

Central Nervous System (CNS) Progression-free Survival(PFS)

The number of patients that are documented to have progression free survival at 3 months after treatment. Progression free is define as \<25% increase in tumor area. PFS will be measured from the date of entry into the trial to the date of documented progression of brain metastases or death.

Time frame: 3 months after treatment