Maintenance Metronomic Chemotherapy for Metastatic Colorectal Carcinoma

Colorectal Cancer Metastatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01668680
• Other study ID #: EMC-0047-11
• Status: Terminated
• Phase: Phase 2
• First received: March 11, 2012
• Last updated: July 6, 2015
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: July 2015
• Source: HaEmek Medical Center, Israel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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:

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Neoplasms

Intervention

Drug:
• CAPECITABINE, CELECOXIB and METHOTREXATE
daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE

Locations

Country	Name	City	State
Israel	HaEmek Medical Center	Afula

Sponsors (2)

Lead Sponsor	Collaborator
HaEmek Medical Center, Israel	Clalit Health Services

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of progression free survival (PFS), measured in 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.	Up to 12 months.	No
Secondary	Toxicity profile of treatment, defined by CTCAE Version 4.0.	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.	up to12 months	Yes
Secondary	Changes in levels of angiogenic factors while under treatment: VEGF, PDGF, TSP-1	Change from baseline in levels of angiogenic factors at 4 months of treatment.	Up to 4 months.	No
Secondary	Quality of life, as expressed by FACT-C.	Change from baseline in parameters of Quality of life until the end of treatment, assessed up to 12 months.	Up to 12 months.	No