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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02280694
Recruitment Status : Active, not recruiting
First Posted : October 31, 2014
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
HaEmek Medical Center, Israel

Tracking Information
First Submitted Date  ICMJE October 29, 2014
First Posted Date  ICMJE October 31, 2014
Last Update Posted Date July 24, 2018
Actual Study Start Date  ICMJE January 2015
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2016)
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. ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 30, 2014)
The progression free survival (PFS) RATIO: PFS on the experimental treatment over PFS on the last (previous) line of treatment [ 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. ]
Change History Complete list of historical versions of study NCT02280694 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Metronomic Poly-chemotherapy for Metastatic CRC
Official Title  ICMJE Metronomic Poly-chemotherapy for Metastatic Colorectal Cancer at Progression Following Established Treatments: Clinical and Laboratory Research
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: Capecitabine
    Other Name: Xeloda
  • Drug: Cyclophosphamide
    Other Name: Endoxan
  • Drug: Methotrexate
    Other Name: Abitrexate, Methotrexat "Ebewe", Metoject medac
  • Drug: Celecoxib
    Other Name: Celebra, Celcox
Study Arms  ICMJE Experimental: capecitabine, cyclophosphamide, methotrexate, celecoxib

The Investigational Product: Route and Dosage Form Ambulatory/oral, continuous but not uniform, DAILY treatment

  1. Tab. CYCLOPHOSPHAMIDE 50mg, 1X1/day ONLY days 1-5 / week; At evening only (at the end of meal)
  2. 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)
  3. Tab. METHOTREXATE 2.5mg, 1x2/day ONLY on days 6-7/week; At morning AND evening (one hour before meal)
  4. Tab. CELECOXIB 200 mg, 1x2/day EVERY day (at the end of meal)
Interventions:
  • Drug: Capecitabine
  • Drug: Cyclophosphamide
  • Drug: Methotrexate
  • Drug: Celecoxib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 22, 2018)
45
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2014)
100
Estimated Study Completion Date  ICMJE January 2019
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02280694
Other Study ID Numbers  ICMJE 0035-14-EMC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party HaEmek Medical Center, Israel
Study Sponsor  ICMJE HaEmek Medical Center, Israel
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ofer Purim, MD Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus, Petach Tiqva, Israel
PRS Account HaEmek Medical Center, Israel
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP