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

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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

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Capecitabine Drug: Cyclophosphamide Drug: Methotrexate Drug: Celecoxib Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Metronomic Poly-chemotherapy for Metastatic Colorectal Cancer at Progression Following Established Treatments: Clinical and Laboratory Research
Actual Study Start Date : January 2015
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)
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




Primary Outcome Measures :
  1. 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. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02280694


Locations
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Israel
Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus,
Petach Tiqva, Israel
Sponsors and Collaborators
HaEmek Medical Center, Israel
Investigators
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Principal Investigator: Ofer Purim, MD Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus, Petach Tiqva, Israel

Publications:
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Responsible Party: HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT02280694     History of Changes
Other Study ID Numbers: 0035-14-EMC
First Posted: October 31, 2014    Key Record Dates
Last Update Posted: July 24, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Celecoxib
Cyclophosphamide
Capecitabine
Methotrexate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents