Metronomic Chemotherapy With Anti-angiogenic Effect as Maintenance Treatment for Metastatic Colorectal Carcinoma Following Response to FOLFIRI+Bevacizumab: Clinical and Laboratory Studies

HaEmek Medical Center, Israel1 site in 1 country80 target enrollmentSeptember 2012

ConditionsColorectal Cancer Metastatic

InterventionsCAPECITABINE, CELECOXIB and METHOTREXATE

DrugsCAPECITABINE, CELECOXIB and METHOTREXATE

Overview

Phase: Phase 2
Intervention: CAPECITABINE, CELECOXIB and METHOTREXATE
Conditions: Colorectal Cancer Metastatic
Sponsor: HaEmek Medical Center, Israel
Enrollment: 80
Locations: 1
Primary Endpoint: Length of progression free survival (PFS), measured in months.
Status: Terminated
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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:

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

Hypothesis:

The re-growth of residual metastases can be slowed by the anti-angiogenic effects of LDM chemotherapy.
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.

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.

Registry

clinicaltrials.gov

Start Date

September 2012

End Date

December 2014

Last Updated

10 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

HaEmek Medical Center, Israel

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologic (or cytologic) proof of colorectal carcinoma (CRC).
•Age: between 18 and
•Sex: both sexes.
•Previous treatment for metastatic disease is limited to FOLFIRI+ bevacizumab.
•Prior adjuvant chemotherapy, with a fluoropyrimidine and/or Oxaliplatin, is allowed.
•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.
•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.
•Asymptomatic patients at break from chemotherapy.
•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).
•Capability to understand and to sign the informed consent.

Exclusion Criteria

•Concurrent any other cancer (except BCC or squamous cell carcinoma of skin).
•Inability to adhere to monthly visits to the oncology unit for evaluation.
•Presence of brain metastases.
•Any current or recent (within the last month) continuous treatment by steroids or by NSAIDs, or with therapeutic doses of anticoagulants for any reason.
•Previous radiotherapy to the only site of measurable disease.
•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).

Arms & Interventions

LDM anti-angiogenic chemotherapy

LDM (Low Dose Metronomic) anti-angiogenic chemotherapy includes daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE.

Intervention: CAPECITABINE, CELECOXIB and METHOTREXATE

Outcomes

Primary Outcomes

Length of progression free survival (PFS), measured in months.

Time Frame: Up to 12 months.

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 Outcomes

Quality of life, as expressed by FACT-C.(Up to 12 months.)
Toxicity profile of treatment, defined by CTCAE Version 4.0.(up to12 months)
Changes in levels of angiogenic factors while under treatment: VEGF, PDGF, TSP-1(Up to 4 months.)