Low Dose Metronomic Poly-chemotherapy for Metastatic CRC (LDMchemoCRC)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer
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)
Sites / Locations
- Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus,
Arms of the Study
Arm 1
Experimental
capecitabine, cyclophosphamide, methotrexate, celecoxib
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)