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

This study has been terminated.
(No satisfactory acrual)
Information provided by (Responsible Party):
LOVEN DAVID, HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier:
First received: February 11, 2010
Last updated: July 6, 2015
Last verified: July 2015

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.

Condition Intervention Phase
Breast Cancer, Metastatic
Drug: Cyclophosphamide, Capecitabine, Methotrexate, Celecoxib, Pamidronate (or Zoledronate)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antiangiogenic Treatment Strategy With Metronomic Chemotherapy Regimen Combined With a Cox-2 Inhibitor and a Bisphosphonate for Patients With Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by HaEmek Medical Center, Israel:

Primary Outcome Measures:
  • To determine the efficacy by rate of clinical benefit (CB): rate of response (RR) + rate of Stable Disease (SD) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma Levels of angiogenic growth factors [ Time Frame: At 4 predetermined time points along treatment period. ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: March 2010
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intervention
same treatment for all patients
Drug: Cyclophosphamide, Capecitabine, Methotrexate, Celecoxib, Pamidronate (or Zoledronate)
  1. Cyclophosphamide Tab. 50mg, 1x1/day, continuously.
  2. Capecitabine Tab. 500mg, 1+2/day, continuously.
  3. Methotrexate Tab. 2.5mg, 1x2/day, 2 days every week.
  4. Celecoxib Tab. 200mg, 1x2/day, continuously.
  5. Pamidronate I.V. 90mg, every 4 weeks; or Zoledronate I.V. 4mg, every 4 weeks)


Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01067989

Oncology unit
Afula, Israel, 18101
Sponsors and Collaborators
HaEmek Medical Center, Israel
  More Information

Responsible Party: LOVEN DAVID, Oncologist, HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT01067989     History of Changes
Other Study ID Numbers: 0078-09-EMC 
Study First Received: February 11, 2010
Last Updated: July 6, 2015
Health Authority: Israel: Ministry of Health

Keywords provided by HaEmek Medical Center, Israel:
metronomic chemotherapy
anti-angiogenic effect
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Zoledronic acid
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Bone Density Conservation Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Nucleic Acid Synthesis Inhibitors
Physiological Effects of Drugs
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 26, 2016