Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast Cancer

NCT01349088 | Withdrawn Phase 1 DMC

• 3 other identifiers: 10G.302009-34JT 1502
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In 2008 there were more than 40,000 deaths caused by metastatic breast cancer in the United States. The development of new treatment strategies is essential to improve outcome for patients with metastatic breast cancer There is significant preclinical and clinical evidence indicating that creating new blood vessels (neoangiogenesis) to provide nutrients to solid tumors, including breast cancer, provides the necessary conditions to allow tumor growth. Vascular endothelial growth factor (VEGF) is one of the important molecules regulating new blood vessel formations and subsequent invasion and metastases. As a result, agents that inhibit VEGF are of substantial interest for the treatment of advanced diseases. This study will further the body of research of motesanib which has been shown in preclinical pharmacology and clinical pharmacology studies to be a potent, orally bioavailable multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, platelet-derived growth factor (PDGF), and Kit receptors.

Conditions

Breast Cancer; Metastatic Breast Cancer; Stage IV Breast Cancer

Keywords

breast cancer; metastatic breast cancer; stage IV breast cancer; motesanib; ixabepilone; capecitabine

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Progression-free survival (PFS) is defined as the time from the date of enrollment to the first occurrence of having documented disease progression or death due to any cause. Evaluation of target lesions and non-target lesions will be in accordance with the RECIST criteria. During the study, assessments of tumor response will take place every 6 weeks. Confirmation of objective response, when applicable, must be performed at a minimum of 4 weeks after the first response has been recorded.

  Up to 3 years or disease progression

Secondary Outcomes (5)

• Maximum Tolerated Dose of Motesanib

  120 days

• Overall Response Rate

  Through 28 days post-treatment

• Toxicity

  Through 28 days post-treatment

• Correlation of Tumor Levels

  Up to 3 years or disease progression

• Pharmacokinetics of Study Regimen

  Through 28 days post-treatment

Study Arms (1)

Motesanib

EXPERIMENTAL

Eligible patients will be enrolled to receive ixabepilone, capecitabine, plus motesanib.

Drug: Ixabepilone; Drug: Capecitabine; Drug: Motesanib

Interventions

Ixabepilone DRUG

Patients will receive ixabepilone at 40 mg/m2.

Also known as: azaepothilone B, BMS-247550

Motesanib

Capecitabine DRUG

Patients will receive capecitabine at 2000 mg/m2.

Also known as: Xeloda

Motesanib

Motesanib DRUG

Patient will receive motesanib at 100mg or 125mg once daily dependent on outcome of Phase I, which will involve the first 3-6 patients.

Also known as: Motesanib diphosphate, AMG 706

Motesanib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the breast regardless of ER, PR and Her2 status with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• Disease progression after at least 1, but no more than 2, prior chemotherapy regimens for metastatic disease.
• Patients with hormone-sensitive tumors must have received prior hormonal therapy and not be amenable to further hormonal therapy.
• Patients with HER2/neu-overexpressing tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) should have received trastuzumab (Herceptin®) and/or lapatinib (Tykerb®) in the adjuvant or metastatic setting (unless contraindicated) and have progressed while on treatment of metastatic disease or within 12 months of completion of adjuvant therapy.
• Patients will eligible if they have tumors that express one of the motesanib-directed tyrosine kinase markers, the target markers:(PDGFR, VEGFR, c-Kit) as determined by study pathologist. Immunohistochemical assays for these markers are provided by grant consortium partner and CLIA-certified diagnostics laboratory MDRG.
• Measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines.
• Complete radiology and tumor measurement within 4 weeks (28 days) prior to enrollment.
• Chest: CT scan with intravenous contrast if the contrast is not medically contraindicated.
• Abdomen: CT scan with intravenous and oral contrast if the contrast is not medically contraindicated.
• Pelvis: CT scan with intravenous and oral contrast if the contrast is not medically contraindicated.
• Brain: CT scan or MRI
• Bone: Whole body Bone Scintigraphy or PET scan
• Female 18 years of age or older at the time the written informed consent is obtained.
• ECOG Performance Status of 0 or 1.
• Adequate organ and hematological function as evidenced by the following laboratory studies within 2 weeks (14 days) of study enrollment, unless stated otherwise:

You may not qualify if:

• Disease Related:
• Current or prior history of central nervous system metastasis.
• Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0 peripheral neuropathy ≥ grade 2 at enrollment.
• Average systolic blood pressure \> 150 mm Hg or average diastolic blood pressure \> 90 mm Hg (average blood pressure of the 3 separate blood pressure values measured according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
• History of arterial or venous thrombosis within 1 year prior to enrollment.
• History of bleeding diathesis or bleeding within 14 days of enrollment.
• Major surgical procedure within 4 weeks (28 days) prior to enrollment.
• Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of enrollment.
• Known positive test for human immunodeficiency virus (HIV), hepatitis C, or malignancy (other than in situ cervical cancer, or basal cell cancer of the skin), unless treated with curative intent and without evidence of disease for ≥ 3 years before study enrollment.
• Clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade II or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or ongoing arrhythmias requiring medication or pacemaker.
• Non-healing wound, ulcer or fracture.
• Ongoing or active infection.
• Known chronic hepatitis.
• Medications:
• Currently or previously treated with small molecule inhibitors of VEGF including, but not limited to, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AZD 6474, AEE-788, BAY 43-9006 (sorafenib) and motesanib.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Susan G. Komen Breast Cancer Foundation: collaborator
• Amgen: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Capecitabine; motesanib diphosphate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Edith Mitchell, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 6, 2011
• Study Start: December 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2018
• Last Updated: May 2, 2025

Record last verified: 2025-05

Locations

US (1)