Epothilone B in Treating Patients With CNS Metastases From Breast Cancer

NCT00450866 | Completed Phase 2 Results DMC

• 3 other identifiers: CASE5106P30CA043703MSKCC-07036
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

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.

Conditions

Breast Cancer; Metastatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months after treatment

Secondary Outcomes (4)

• Toxicity as Measured by NCI CTCAE v3.0

  3 months after treatment

• CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria

  3 months after treatment

• Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria

  3 months after treatment

• Overall Survival

  48 months from start of study

Study Arms (1)

Epothilone B

EXPERIMENTAL

Biological: epothilone B

Interventions

epothilone B BIOLOGICAL

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.

Also known as: Patupilone

Epothilone B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• David Peereboom, MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Meningeal Carcinomatosis; Breast Neoplasms, Male

Interventions

epothilone B

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Meningeal Neoplasms

Results Point of Contact

• Title: David Peereboom, MD
• Organization: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

peerebd@ccf.org

216-445-6068

Study Officials

• David M. Peereboom, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Joseph Baar, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: January 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: May 1, 2012
• Last Updated: February 28, 2014
• Results First Posted: October 9, 2013

Record last verified: 2014-01

Locations

US (5)