Low-Dose/Metronomic(LDM)Chemotherapy for Metastatic Breast Cancer

Antiangiogenic Treatment Strategy With Metronomic Chemotherapy Regimen Combined With a Cox-2 Inhibitor and a Bisphosphonate for Patients With Metastatic Breast Cancer

Low-dose metronomic(LDM)chemotherapy as well as anti-inflammatory agents and bisphosphonates have shown anti-angiogenic properties on tumor vasculature.

This study is meant to test the therapeutic potential of an anti-angiogenic treatment strategy by combining all these agents for metastatic breast cancer patients.

Study Overview

• Status: Terminated
• Conditions: Chemotherapy; Breast Cancer, Metastatic
• Intervention / Treatment: Drug: Cyclophosphamide, Capecitabine, Methotrexate, Celecoxib, Pamidronate (or Zoledronate)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel, 18101
    • Oncology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologic proof of infiltrating duct carcinoma of breast.
• Her-2 negative tumors.
• ECOG performance status: 0-1.
• Presence of measurable disease: primary and/or metastatic.
• CBC showing normal values or any toxicity limited to grade I.
• SMA showing liver and renal functions < 1.5 normal values
• previous treatment with an anthracycline and with a taxane is mandatory either as neoadjuvant/adjuvant treatment or for metastatic disease.
• previous treatment by chemotherapy for metastatic disease is allowed (up to three lines, allowing for MTD Capecitabine to be one of them).
• previous treatment by a bisphosphonate is allowed. However,those patients who up to the study had not received any bisphosphonate and those who had received Clodronate- will receive Pamidronate; those who had been under Pamidronate- will receive Zoledronate; those who had been under Zoledronate- will continue with it."
• The patient's signature on the informed consent.

Exclusion Criteria:

• Her-2 neu positive tumor
• Inability to visit the clinic for outpatient treatment and evaluation
• Active/symptomatic brain metastases.
• ECOG performance status: 2-4.
• Presence of Hand -Foot syndrome, at grade > 2.
• CBC with any grade >2 toxicity
• SMA showing liver functions > 1.5 normal values
• SMA showing renal functions > normal values -Current continuous treatment by steroids or by NSAIDs, or by anti- coagulants for "non protocol" reasons.
• presence of exclusively non-measurable disease (I/E: exclusive bone disease with non-representative tumor markers).
• previous radiotherapy to the "only measurable disease".
• pleural or peritoneal effusion that may represent a "third space".
• history of active peptic ulcer.
• symptomatic coronary heart disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention; same treatment for all patients	Drug: Cyclophosphamide, Capecitabine, Methotrexate, Celecoxib, Pamidronate (or Zoledronate); Cyclophosphamide Tab. 50mg, 1x1/day, continuously.; Capecitabine Tab. 500mg, 1+2/day, continuously.; Methotrexate Tab. 2.5mg, 1x2/day, 2 days every week.; Celecoxib Tab. 200mg, 1x2/day, continuously.; Pamidronate I.V. 90mg, every 4 weeks; or Zoledronate I.V. 4mg, every 4 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the efficacy by rate of clinical benefit (CB): rate of response (RR) + rate of Stable Disease (SD)	6 and 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Levels of angiogenic growth factors	At 4 predetermined time points along treatment period.

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 11, 2010
• First Submitted That Met QC Criteria: February 11, 2010
• First Posted (Estimate): February 12, 2010

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: July 6, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Breast cancer; metronomic chemotherapy; anti-angiogenic effect
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Bone Density Conservation Agents; Reproductive Control Agents; Cyclooxygenase 2 Inhibitors; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cyclophosphamide; Capecitabine; Celecoxib; Methotrexate; Zoledronic Acid; Pamidronate
• Other Study ID Numbers: 0078-09-EMC