Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving paclitaxel albumin-stabilized nanoparticle formulation together with everolimus may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with paclitaxel albumin-stabilized nanoparticle formulation and to see how well it works in treating women with locally advanced or metastatic breast cancer.

Further Study Information

OBJECTIVES:

Primary

• To determine the maximum tolerated dose and recommended phase II dose of everolimus when administered in combination with paclitaxel albumin-stabilized nanoparticle formulation in women with locally advanced or metastatic breast cancer. (Phase I)

• To determine the antitumor activity of this regimen, as measured by clinical tumor response according to RECIST criteria, in these patients. (Phase II)

Secondary

• To determine the safety and tolerability of everolimus when administered at the recommended phase II dose in combination with paclitaxel albumin-stabilized nanoparticle formulation in these patients.

OUTLINE: This is a multicenter, phase I dose-escalation study of everolimus followed by a phase II study.

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Patients also receive oral everolimus once daily or once every other day on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Locally recurrent or metastatic disease

• Not amenable to surgery or radiotherapy

• HER2/neu-negative disease

• Has ≥ 1 measurable lesion, as defined by RECIST criteria

• No non-measurable lesions (e.g., pleural effusion or ascites) other than bone metastases

• Bone metastases as the sole site of disease allowed provided there are ≥ 2 lytic bone lesions by x-ray, CT scan, or MRI

• Lesions irradiated in the advanced setting are not considered sites of measurable disease unless clear tumor progression has been documented in these lesions since the completion of radiotherapy

• No bilateral diffuse lymphangitis carcinomatosa of the lung (> 50% of lung involvement) or evidence of liver metastases estimated as involving > one third of the liver by sonogram and/or CT scan

• No unstable CNS metastases

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• ECOG performance status 0-2

• Life expectancy ≥ 3 months

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin > 9 g/dL

• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN in patients with liver metastases)

• INR < 1.5 times ULN

• Serum creatinine ≤ 1.5 mg/dL

• Fasting serum cholesterol ≤ 300 mg/dL (or 7.75 mmol/L) (levels outside this threshold allowed provided statin therapy is initiated)

• Fasting triglycerides ≤ 2.5 times ULN (levels outside this threshold allowed provided statin therapy is initiated)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Oral, implantable, or injectable contraceptives are not considered effective contraception

• No ascites or encephalopathy due to liver disease

• No neuropathy ≥ grade 2

• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of everolimus, including any of the following:

• Ulcerative disease

• Uncontrolled nausea, vomiting, or diarrhea

• Malabsorption syndrome

• No active, bleeding diathesis

• No known HIV seropositivity

• No known hypersensitivity to everolimus or sirolimus (rapamycin), paclitaxel albumin-stabilized nanoparticle formulation, or lactose

• No history of noncompliance to medical regimens

• No severe and/or uncontrolled medical condition or other condition that could affect study participation, including any of the following:

• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the past 6 months, or serious uncontrolled cardiac arrhythmia

• Severely impaired lung function

• Active (acute or chronic) or uncontrolled infections or disorders

• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by study treatment

• Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)

• No other malignancies within the past 5 years, except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

• Prior systemic endocrine therapy for advanced breast cancer allowed

• No prior chemotherapy for advanced breast cancer

• Prior adjuvant chemotherapy allowed

• No prior small bowel resection

• More than 5 days since prior strong CYP3A inhibitors or inducers (e.g., rifabutin, rifampin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, or telithromycin)

• More than 30 days since prior radiotherapy and recovered (alopecia allowed)

• Prior localized radiotherapy for analgesic purposes allowed provided radiotherapy has been completed and the patient's condition is stabilized

• No prior radiotherapy to ≥ 25% of the bone marrow

• More than 30 days since prior investigational drugs

• More than 1 week since prior and no concurrent immunization with attenuated live vaccines

• No concurrent oral anti-vitamin K medication, except low-dose coumadin

• No concurrent systemic steroids or other immunosuppressive agents as chronic therapy

• Topical applications, inhaled sprays, eye drops, or local injections allowed

• A short duration (< 2 weeks) of systemic corticosteroids allowed

• No concurrent hormone replacement therapy, topical estrogens (including any intra-vaginal preparations), megestrol acetate, or selective estrogen-receptor modulators (e.g., raloxifene)

• No other concurrent investigational or anticancer agents

• Concurrent antiangiogenic agents allowed

• Concurrent bisphosphonates allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Deborah L. Toppmeyer

Principal Investigator

Mary Surman, RN		Ph: 732-235-9473
		Email: surmanma@umdnj.edu

Christine Tierney, RN		Ph: 732-235-9473
		Email: tiernecl@umdnj.edu

U.S.A.
New Jersey
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Clinical Trials Office - Cancer Institute of New Jersey	Ph: 732-235-8675

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00934895
Information obtained from ClinicalTrials.gov on December 14, 2011

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