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

• Register: ClinicalTrials.gov
• Last refreshed on: 13 May 2013
• Main ID: NCT01349088
• Date of registration: 04/05/2011
• Primary sponsor: Thomas Jefferson University
• Public title: Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast Cancer
• Scientific title: Phase I/II Trial of Motesanib in Combination With Ixabepilone and Capecitabine in Women With Locally Recurrent or Metastatic Breast Cancer
• Date of first enrolment: October 2007
• Target sample size: 74
• Recruitment status: Not yet recruiting
• URL: http://clinicaltrials.gov/show/NCT01349088
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Edith Mitchell, MD

• Name: Edith Mitchell, MD

• Name: Edith Mitchell, MD
• Affiliation: Thomas Jefferson University

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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:

- Cardiac function, as follows:

- Normal sinus rhythm (no significant ECG changes)

- Left ventricular ejection fraction = Lower Limit of Normal, as determined
by echocardiogram or MUGA scan, according to institutional standards within
28 days prior to study enrollment.

- Hematological function, as follows:

- Absolute neutrophil count = 1.5 x 109/L

- Platelet count = 100 x 109/L and = 850 x 109/L

- Hemoglobin = 9 g/dL.

- PTT and INR < 1.5 x ULN.

- Renal function, as follows:

- Serum creatinine = 175 µmol/L (= 2mg/dL). If creatinine is between 140-175
µmol/L, creatinine clearance (calculated or measured) should be > 40
mL/min.

- Urinary protein quantitative value of = 30 mg/dL in urinalysis or = 1 + on
dipstick unless protein is < 500 mg in a 24-hour urine sample.

- Hepatic function, as follows:

- Aspartate aminotransferase (AST) = 2.5 x ULN

- Alanine aminotransferase (ALT) = 2.5 x ULN

- Total bilirubin = 1 x ULN

- Patients of child-bearing potential and sexually active must provide a negative
pregnancy test within 7 days prior to enrollment.

- More than 4 weeks since prior therapy for breast cancer

- No other concurrent investigational or commercial agents or therapies for metastatic
breast cancer

- No prior capecitabine or fluorouracil for metastatic breast cancer

- More than 4 weeks since prior radiotherapy **Previously irradiated area(s) must not
be the only site of disease**

- More than 4 weeks since prior major surgery

Exclusion Criteria:

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.

- Treatment with rifampin, carbamazepine, rifabutin or phenobarbital within 14 days
prior to study enrollment.

- Treatment with strong CYP 3A inhibitors or inducers such as ketoconazole,
itraconazole, fluconazole, clarithromycin, erythromycin, nefazodone, or any HIV
protease inhibitors within 7 days prior to study enrollment.

- Treatment with immune modulators such as cyclosporine and tacrolimus within 7 days
prior to study enrollment.

- Treatment with herbal medications containing St. John's Wort within 7 days prior to
study enrollment.

- Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other
selective estrogen receptor modulators (SERMS), given for breast cancer prevention or
for osteoporosis. Patients must have discontinued these agent


Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Breast Cancer

Metastatic Breast Cancer

Stage IV Breast Cancer

Intervention(s)

Drug: Capecitabine

Drug: Ixabepilone

Drug: Motesanib

Primary Outcome(s)

Progression-Free Survival [Time Frame: Up to 3 years or disease progression]

Secondary Outcome(s)

Correlation of Tumor Levels [Time Frame: Up to 3 years or disease progression]

Maximum Tolerated Dose of Motesanib [Time Frame: 120 days]

Overall Response Rate [Time Frame: Through 28 days post-treatment]

Pharmacokinetics of Study Regimen [Time Frame: Through 28 days post-treatment]

Toxicity [Time Frame: Through 28 days post-treatment]

Secondary ID(s)

10G.30

2009-34

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Amgen

Susan G. Komen Breast Cancer Foundation