Low Dose Metronomic Poly-chemotherapy for Metastatic CRC

NCT02280694 | Completed Phase 2 DMC

• 1 other identifier: 0035-14-EMC
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• The median progression free survival (mPFS)

  Base line and every consecutive 8 weeks, up to disease progression or exit from study for any other cause, up to 18 months.

Study Arms (1)

capecitabine, cyclophosphamide, methotrexate, celecoxib

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Methotrexate; Drug: Celecoxib

Interventions

Capecitabine DRUG

Also known as: Xeloda

capecitabine, cyclophosphamide, methotrexate, celecoxib

Cyclophosphamide DRUG

Also known as: Endoxan

capecitabine, cyclophosphamide, methotrexate, celecoxib

Methotrexate DRUG

Also known as: Abitrexate, Methotrexat "Ebewe", Metoject medac

capecitabine, cyclophosphamide, methotrexate, celecoxib

Celecoxib DRUG

Also known as: Celebra, Celcox

capecitabine, cyclophosphamide, methotrexate, celecoxib

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• HaEmek Medical Center, Israel: lead

Study Sites (1)

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

Petach Tiqva, Israel

Location

Related Publications (1)

• 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.

  PMID: 20921468 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Capecitabine; Cyclophosphamide; Methotrexate; Celecoxib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Sulfones; Sulfur Compounds; Pyrazoles; Azoles

Study Officials

• Ofer Purim, MD

  Gastrointestinal Oncology Unit, Institute of Oncology, Davidoff Center, Rabin Medical Center, Belinson Campus, Petach Tiqva, Israel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: October 31, 2014
• Study Start: January 1, 2015
• Primary Completion: January 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 12, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)