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Low Dose Metronomic Poly-chemotherapy for Metastatic CRC (LDMchemoCRC)

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Capecitabine
Cyclophosphamide
Methotrexate
Celecoxib
Sponsored by
HaEmek Medical Center, Israel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histological (or cytological) proof of colorectal carcinoma (CRC)
  2. Measurable metastases
  3. ECOG (Eastern Cooperative Oncology Group) performance status 0-2
  4. Progressing disease following all available chemotherapy treatment lines (including chemotherapy, bevacizumab+/-ziv-aflibercept, and an epidermal growth factor receptor (EGFR) inhibitor [if WT(wild type)-KRAS]

  5. The central-radiologist's confirmation of PD* under the last (previous) line of "conventional treatment".

    * PD (progressive disease) by RECIST(Response Evaluation Criteria in Solid Tumors) criteria : a) there is 20% or more relative increment in the sum of diameters of target lesions in comparison with the base line sum, and their absolute increase is 5 mm. or more, or b) there appeared one or more new lesions, or c)there is substantial worsening in non-target disease

  6. Age: between 18 and 85
  7. Prior radiotherapy either as adjuvant treatment or for palliation is allowed, unless this was delivered to the only measurable lesion
  8. Complete blood count reflecting adequate Bone Marrow:

Hb=/ > 9 g/dL, ANC=/> 1,500 Plt =/> 75,000/mcL; 9. Adequate liver function:

  1. Total Bilirubin always =/<X1.5 ULN
  2. ALT and AST and Alkaline Phosphatase =/ < 2.5 X upper normal limit , although in patients with liver metastases these are acceptable if =/< 5 X ULN; 11. Adequate renal function (serum creatinine): =/< 1.5 X ULN. 12. Absence of any non-hematological toxicity at grade 2 or higher. 13.The patient is able to understand and ready to sign the informed consent

Exclusion Criteria:

  1. Lack of confirmation of PD (under the pre-study treatment) by the central radiologist
  2. Any concurrent other active cancer (except basal cell or squamous cell carcinoma of skin and early prostate cancer or DCIS- in situ breast cancer)
  3. Inability to adhere to monthly visits to the oncological unit for evaluation
  4. Presence of brain metastases
  5. Continuous treatment with steroids or with NSAIDs or with anticoagulants during the last year (except micropirin)
  6. Previous radiotherapy to the only site of measurable disease
  7. Existence of active peptic ulcer or symptomatic coronary disease
  8. Existence of chronic inflammatory diseases, such as ulcerative colitis or Crohn's disease or rheumatoid arthritis
  9. Presence of ascites, and/or any other "third space" finding (eg. significant leg edema)

Sites / Locations

  • Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus,

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

capecitabine, cyclophosphamide, methotrexate, celecoxib

Arm Description

The Investigational Product: Route and Dosage Form Ambulatory/oral, continuous but not uniform, DAILY treatment Tab. CYCLOPHOSPHAMIDE 50mg, 1X1/day ONLY days 1-5 / week; At evening only (at the end of meal) Tab. CAPECITABINE 500mg, fixed dose of 1500mg/day (1000mg at morning + 500mg at evening) ONLY on days 1-5 / week; At morning AND at evening (at the end of meals) Tab. METHOTREXATE 2.5mg, 1x2/day ONLY on days 6-7/week; At morning AND evening (one hour before meal) Tab. CELECOXIB 200 mg, 1x2/day EVERY day (at the end of meal)

Outcomes

Primary Outcome Measures

The median progression free survival (mPFS)

Secondary Outcome Measures

Full Information

First Posted
October 29, 2014
Last Updated
February 11, 2020
Sponsor
HaEmek Medical Center, Israel
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1. Study Identification

Unique Protocol Identification Number
NCT02280694
Brief Title
Low Dose Metronomic Poly-chemotherapy for Metastatic CRC
Acronym
LDMchemoCRC
Official Title
Metronomic Poly-chemotherapy for Metastatic Colorectal Cancer at Progression Following Established Treatments: Clinical and Laboratory Research
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
January 2019 (Actual)
Study Completion Date
December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HaEmek Medical Center, Israel

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study investigates the activity of a new regimen of treatment for patients with metastatic colorectal carcinoma. This includes a combination of well-known chemotherapy agents and anti-inflammatory agents, when administered orally at low daily doses and without planed brakes (Low Dose Metronomic regimen), in contrast with the conventional and already exhausted regimens of treatment at Maximal Tolerated Doses (MTD) which required pre-planned brakes between treatment days.
Detailed Description
Patients suffering from metastases of colorectal cancer whose tumor cells develop resistance to conventionally administered treatments are in need for new methods of treatment. While their chemotherapy had been administered up till then at the classical regimen of Maximal Tolerated Doses (MTD), which is aimed to directly killing maximal fractions of tumor cells, the present study evaluates the clinical benefit of a treatment which is based on old chemotherapeutic and old anti-inflammatory drugs, when these are administered at low doses,on daily basis and orally taken, without planed brakes (Low Dose Metronomic regimen). Treatments based on this type of regimen have already been studied on other models of cancer and showed the capacity of suppressing tumor growth by a new category of anti-tumor effects. Namely, by affecting factors and mechanisms which prevail in the microenvironment that surrounds tumor deposits, thus circumventing the resistance of their cancer cells to chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
capecitabine, cyclophosphamide, methotrexate, celecoxib
Arm Type
Experimental
Arm Description
The Investigational Product: Route and Dosage Form Ambulatory/oral, continuous but not uniform, DAILY treatment Tab. CYCLOPHOSPHAMIDE 50mg, 1X1/day ONLY days 1-5 / week; At evening only (at the end of meal) Tab. CAPECITABINE 500mg, fixed dose of 1500mg/day (1000mg at morning + 500mg at evening) ONLY on days 1-5 / week; At morning AND at evening (at the end of meals) Tab. METHOTREXATE 2.5mg, 1x2/day ONLY on days 6-7/week; At morning AND evening (one hour before meal) Tab. CELECOXIB 200 mg, 1x2/day EVERY day (at the end of meal)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Endoxan
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Abitrexate, Methotrexat "Ebewe", Metoject medac
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebra, Celcox
Primary Outcome Measure Information:
Title
The median progression free survival (mPFS)
Time Frame
Base line and every consecutive 8 weeks, up to disease progression or exit from study for any other cause, up to 18 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological (or cytological) proof of colorectal carcinoma (CRC) Measurable metastases ECOG (Eastern Cooperative Oncology Group) performance status 0-2 Progressing disease following all available chemotherapy treatment lines (including chemotherapy, bevacizumab+/-ziv-aflibercept, and an epidermal growth factor receptor (EGFR) inhibitor [if WT(wild type)-KRAS] The central-radiologist's confirmation of PD* under the last (previous) line of "conventional treatment". * PD (progressive disease) by RECIST(Response Evaluation Criteria in Solid Tumors) criteria : a) there is 20% or more relative increment in the sum of diameters of target lesions in comparison with the base line sum, and their absolute increase is 5 mm. or more, or b) there appeared one or more new lesions, or c)there is substantial worsening in non-target disease Age: between 18 and 85 Prior radiotherapy either as adjuvant treatment or for palliation is allowed, unless this was delivered to the only measurable lesion Complete blood count reflecting adequate Bone Marrow: Hb=/ > 9 g/dL, ANC=/> 1,500 Plt =/> 75,000/mcL; 9. Adequate liver function: Total Bilirubin always =/<X1.5 ULN ALT and AST and Alkaline Phosphatase =/ < 2.5 X upper normal limit , although in patients with liver metastases these are acceptable if =/< 5 X ULN; 11. Adequate renal function (serum creatinine): =/< 1.5 X ULN. 12. Absence of any non-hematological toxicity at grade 2 or higher. 13.The patient is able to understand and ready to sign the informed consent Exclusion Criteria: Lack of confirmation of PD (under the pre-study treatment) by the central radiologist Any concurrent other active cancer (except basal cell or squamous cell carcinoma of skin and early prostate cancer or DCIS- in situ breast cancer) Inability to adhere to monthly visits to the oncological unit for evaluation Presence of brain metastases Continuous treatment with steroids or with NSAIDs or with anticoagulants during the last year (except micropirin) Previous radiotherapy to the only site of measurable disease Existence of active peptic ulcer or symptomatic coronary disease Existence of chronic inflammatory diseases, such as ulcerative colitis or Crohn's disease or rheumatoid arthritis Presence of ascites, and/or any other "third space" finding (eg. significant leg edema)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ofer Purim, MD
Organizational Affiliation
Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus, Petach Tiqva, Israel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus,
City
Petach Tiqva
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20921468
Citation
Von Hoff DD, Stephenson JJ Jr, Rosen P, Loesch DM, Borad MJ, Anthony S, Jameson G, Brown S, Cantafio N, Richards DA, Fitch TR, Wasserman E, Fernandez C, Green S, Sutherland W, Bittner M, Alarcon A, Mallery D, Penny R. Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010 Nov 20;28(33):4877-83. doi: 10.1200/JCO.2009.26.5983. Epub 2010 Oct 4.
Results Reference
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Low Dose Metronomic Poly-chemotherapy for Metastatic CRC

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