Official Title: “A Multi-Center, Open-Label, Single-Arm Phase II Trial Assessing the Efficacy and Safety of Weekly Bolus Infusions of 5-Fluorouracil Combined With CoFactor (5-10 Methylenetetrahydrofolate) in Advanced Breast Cancer Patients Who Failed Anthracycline and Taxane Chemotherapy Regimens”

A multi-center, open-label, single-arm Phase II trial assessing the efficacy and safety of weekly bolus infusions of 5-fluorouracil combined with CoFactor (5-10 methylenetetrahydrofolate) in advanced breast cancer patients who failed anthracycline and taxane chemotherapy regimens.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: CoFactor (ANX-510)

Primary Measures

• Overall Response Rate

Secondary Measures

• Progression Free Survival
• Overall Survival
• Duration of Response

Inclusion Criteria:

• Signed informed consent.
• Women with a histologically/cytologically proven diagnosis of advanced adenocarcinoma of the breast.
• Measurable disease. At least one unidimensionally measurable non-bony lesion with a diameter >=10 mm using spiral CT scans (use of spiral CT must be documented in medical records and used consistently throughout the study) or >= 20 mm using conventional CT or MRI scans outside the irradiated area according to RECIST criteria.
• Patients having failed both prior anthracycline and taxane derivative chemotherapy regimens. Anthrocycline and Taxane failure definitions as defined in the protocol.
• No more than two prior chemotherapy regimens for advanced disease.
• Performance status (ECOG) <= 2 or Karnofsky >= 70
• Age >= 18 years.
• Life expectancy >= 12 weeks.
• Adequate organ function as shown by the following:
• 1. WBCs >= 3.0 x 109/L, absolute neutrophil count (ANC)>= 1.5 x 109/L, platelets >= 100 x 109/L, hemoglobin >= 9 g/dL
• 2. Bilirubin <= 1.25 x the upper limit of normal (ULN),aspartate aminotransferase(AST or alanine aminotransferase(ALT),= 3 x ULN (or <= 5 x ULN in case of liver metastases)
• 3. Serum calcium within normal limits
• 4. Serum albumin within the normal range for the study site
• 5. Creatinine clearance >= 60 mL/min (Cockroft and Gault)
• 6. Left ventricular ejection fraction (LVEF) within normal limits as shown by echocardiography or scintigraphy (multiple-gated acquisition scan).
• Patients of childbearing potential must be using medically acceptable contraception for 4 weeks before start of study treatment and 4 months after study treatment completion. Patients of childbearing potential must have a negative pregnancy test result within 7 days prior to study treatment initiation.
• Patients with parenchymal brain metastases must be either adequately controlled following resection or completed appropriate radiation therapy and be receiving a stable corticosteroid dose prior to study entry. Patients with leptomeningeal involvement should not be included in the study.

Exclusion Criteria:

• Her2/neu positive tumor (2+ or 3+).
• Pregnancy or lactation
• Systemic cytotoxic anti-cancer therapy within <=4 weeks of study entry, or 6 weeks if the systemic therapy contains a nitrosourea or mitomycin C. Hormonal anti-cancer treatment must be ongoing, or must have been discontinued >3 months before study entry.
• Prior 5-FU- and/or capecitabine-based palliative chemotherapy.
• Extensive prior radiotherapy affecting more than 30% of bone marrow reserves, or bone marrow / stem cell transplantation.
• Participation in clinical studies of non-approved experimental agents or procedures within <=4 weeks of study entry.
• History of other malignancy, unless cured and the patient has been disease-free for
• >=2 years. Patients with a history of cervical carcinoma in situ or cured stage I cervical cancer, or of epidermal or basal cell skin cancer, may be eligible for enrollment after discussion with the sponsor.
• Previous unexpected reaction to fluoropyrimidines, with or without documented deficiency of dihydropyrimidine dehydrogenase, or known hypersensitivity to 5-FU.
• Psychologic, familial, sociologic or geographic conditions which do not permit compliance with the study protocol and/or study.
• Significant cardiac disease, including symptomatic ventricular arrhythmia, congestive heart failure, myocardial infarction within 12 months before study entry.
• Concomitant treatment with any experimental drug or anti-cancer drug, except hormone therapy or bisphosphonates.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Adventrx Pharmaceuticals

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00434369

Study ID Number: 510-08

ClinicalTrials.gov Identifier: NCT00434369

Health Authority: United States: Food and Drug Administration