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Maintenance Metronomic Chemotherapy for Metastatic Colorectal Carcinoma

This study is not yet open for participant recruitment.
Verified August 2012 by HaEmek Medical Center, Israel
Sponsor:
Collaborator:
Clalit Health Services
Information provided by (Responsible Party):
HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier:
NCT01668680
First received: March 11, 2012
Last updated: August 16, 2012
Last verified: August 2012
History of Changes
  Purpose

Colorectal cancer patients with metastases (mCRC) at response under expensive chemotherapy which may be toxic +/- exhausting are candidates for an effective and more convenient maintenance treatment.

Objectives:

  1. To define the efficacy of maintenance chemotherapy by a low-dose metronomic (LDM) regimen, in metastatic CRC patients responding under FOLFIRI + bevacizumab.
  2. To discover predictive factors for response to this LDM regimen.

Hypothesis:

  1. The re-growth of residual metastases can be slowed by the anti-angiogenic effects of LDM chemotherapy.
  2. Serial measurements of angiogenic/ inflammatory factors in the plasma and/or evaluation of certain enzymes in the tumor may discover predictive factors of response to LDM chemotherapy in metastatic CRC patients.

Condition Intervention Phase
Colorectal Cancer Metastatic
 Drug: CAPECITABINE, CELECOXIB and METHOTREXATE
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Metronomic Chemotherapy With Anti-angiogenic Effect as Maintenance Treatment for Metastatic Colorectal Carcinoma Following Response to FOLFIRI+Bevacizumab: Clinical and Laboratory Studies

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Length of progression free survival (PFS), measured in months. [ Time Frame: Up to 12 months. ] [ Designated as safety issue: No ]
    From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.


Secondary Outcome Measures:
  • Toxicity profile of treatment, defined by CTCAE Version 4.0. [ Time Frame: up to12 months ] [ Designated as safety issue: Yes ]
    From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.

  • Changes in levels of angiogenic factors while under treatment: VEGF, PDGF, TSP-1 [ Time Frame: Up to 4 months. ] [ Designated as safety issue: No ]
    Change from baseline in levels of angiogenic factors at 4 months of treatment.

  • Quality of life, as expressed by FACT-C. [ Time Frame: Up to 12 months. ] [ Designated as safety issue: No ]
    Change from baseline in parameters of Quality of life until the end of treatment, assessed up to 12 months.


Estimated Enrollment: 80
Study Start Date: September 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDM anti-angiogenic chemotherapy
LDM (Low Dose Metronomic) anti-angiogenic chemotherapy includes daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE.
 Drug: CAPECITABINE, CELECOXIB and METHOTREXATE
daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE
Other Name: Metronomic Chemotherapy
No Intervention: observation
observation only

Detailed Description:

At entry to the research protocol the up-till then administered treatment with Intra Venous FOLFIRI+BEVACIZUMAB will be stopped.Instead, the research oral treatment will be initiated to be taken daily on an ambulatory basis and under once monthly re-evaluation. If and when disease progresses the original FOLFIRI+BEVACIZUMAB treatment will be considered for re-institution.

  Eligibility

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

Inclusion Criteria:

  1. Histologic (or cytologic) proof of colorectal carcinoma (CRC).
  2. Age: between 18 and 80.
  3. Sex: both sexes.
  4. Previous treatment for metastatic disease is limited to FOLFIRI+ bevacizumab.
  5. Prior adjuvant chemotherapy, with a fluoropyrimidine and/or Oxaliplatin, is allowed.
  6. Prior radiotherapy, either as adjuvant treatment or palliation of metastatic sites is allowed, provided that there are other non-irradiated foci of disease for evaluation.
  7. Persistent remission, either complete, partial or minimal response (CR, PR or MR) or stable disease (SD), one year+/-one month from initiation of first line treatment for mCRC.
  8. Asymptomatic patients at break from chemotherapy.
  9. Intact organ function, including complete blood counts (CBC) showing normal values or any toxicity limited to grade 1 and blood chemistry (SMA) showing liver and renal functions < 1.5 upper normal limit (UNL).
  10. Capability to understand and to sign the informed consent.

Exclusion Criteria:

  1. Concurrent any other cancer (except BCC or squamous cell carcinoma of skin).
  2. Inability to adhere to monthly visits to the oncology unit for evaluation.
  3. Presence of brain metastases.
  4. Any current or recent (within the last month) continuous treatment by steroids or by NSAIDs, or with therapeutic doses of anticoagulants for any reason.
  5. Previous radiotherapy to the only site of measurable disease.
  6. Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac including arrhythmias, hepatic or renal disease), and/or existence of active peptic ulcer (clinically and/or by gastroscopy).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01668680

Contacts
Contact: David Loven, MD 972-52-2544562 loven_da@clalit.org.il
Contact: Baruch Brenner, MD 972-50-4065452 brennerb@clalit.org.il

Locations
Israel
HaEmek Medical Center Not yet recruiting
Afula, Israel, 18101
Contact: Baruch Brenner, MD         brennerb@clalit.org.il    
Sub-Investigator: Ofer Purim, MD            
Sponsors and Collaborators
HaEmek Medical Center, Israel
Clalit Health Services
Investigators
Principal Investigator: David Loven, MD Ha'Emek MC
  More Information

No publications provided

Responsible Party: HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT01668680     History of Changes
Other Study ID Numbers: EMC-0047-11
Study First Received: March 11, 2012
Last Updated: August 16, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by HaEmek Medical Center, Israel:
Metronomic Chemotherapy
Anti-Angiogenic
Maintenance Treatment
Colorectal Cancer Metastatic

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms
Neoplasms, Second Primary
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
 Methotrexate
Capecitabine
Celecoxib
Angiogenesis Inhibitors
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on May 22, 2013