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Maintenance Bevacizumab Only or Bevacizumab Plus Metronomic Chemotherapy in Advanced Colorectal Cancer (MOMA)

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: NCT02271464
Recruitment Status : Completed
First Posted : October 22, 2014
Last Update Posted : December 7, 2017
Sponsor:
Information provided by (Responsible Party):
Alfredo Falcone, Azienda Ospedaliero, Universitaria Pisana

Tracking Information
First Submitted Date  ICMJE October 20, 2014
First Posted Date  ICMJE October 22, 2014
Last Update Posted Date December 7, 2017
Study Start Date  ICMJE March 2012
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2014)
progression-free survival (PFS) [ Time Frame: up to 4 years ]
PFS is defined as the time from randomization to first documentation of objective disease progression or death due to any cause, whichever occurs first.PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive,on study and progression free at the time of the analysis.Alive patients having no tumor assessments after baseline will have time to event endpoint censored on the date of randomization.Disease status will be evaluated according to RECIST 1.1 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02271464 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2014)
  • Best overall response rate (ORR) [ Time Frame: up to 4 years ]
    It is defined as the percentage of patients,relative to the total of enrolled subjects,achieving a complete or partial response, according to RECIST 1.1 criteria,during the induction and the maintenance phases of treatment.The determination of clinical response will be based on investigator reported measurements that will be subsequently confirmed by a central review.Responses will be evaluated every 8 weeks.Patients who do not have an on-study assessment will be included in the analysis as non responders.
  • Duration of response [ Time Frame: up to 4 years ]
    it is defined as the time from the date when measurement criteria are met for CR or PR until first documentation of objective disease progression
  • Resection rate [ Time Frame: up to 4 years ]
    it is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases during treatment or after its completion. Secondary R0 surgery is defined as microscopically margin-free complete surgical removal of all residual disease, allowed by tumoral shrinkage and/or disappearance of one or more lesions.
  • Time to strategy failure (TSF) [ Time Frame: up to 4 years ]
    it is defined as the time from the day of randomization to one of the followings:
    1. progression during FOLFOXIRI + bevacizumab or during a modified FOLFOXIRI + bevacizumab regimen; OR
    2. progression and decision to not administer FOLFOXIRI + bevacizumab or a modified FOLFOXIRI + bevacizumab regimen; OR
    3. introduction of a new agent not included in the study treatment according to randomization arm; OR
    4. death; whichever occurs first.For patients still on-treatment at the time of analysis, the time to strategy failure will be censored on the last date the patients were known to be alive.
  • Time to 2nd progressive disease [ Time Frame: up to 4 years ]
    it is defined as the time from randomization to second documentation of objective disease progression or death due to any cause, whichever occurs first. Time to 2nd progressive disease will be censored on the date of the last evaluable on-study tumor assessment documenting absence of progressive disease for patients who are alive, on study and second progression-free at the time of the analysis. Alive patients having no tumor assessments after baseline will have time to event endpoint censored on the date of randomization.
  • Overall survival (OS) [ Time Frame: up to 4 years ]
    it is defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.
  • Toxicity rate [ Time Frame: up to 4 years ]
    it is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.
  • Overall toxicity rate [ Time Frame: up to 4 years ]
    it is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Maintenance Bevacizumab Only or Bevacizumab Plus Metronomic Chemotherapy in Advanced Colorectal Cancer
Official Title  ICMJE Phase II Randomized Study of Maintenance Treatment With Bevacizumab or Bevacizumab Plus Metronomic Chemotherapy After First-line Induction FOLFOXIRI Plus Bevacizumab for Metastatic Colorectal Cancer Patients
Brief Summary

This study consist of 4-months induction first-line chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab followed by maintenance with bevacizumab or bevacizumab plus metronomic chemotherapy (with capecitabine and cyclophosphamide) in mCRC patients.

The main objective of this study is to preliminarily evaluate the potential effects of the combination of a metronomic chemotherapy with capecitabine and cyclophosphamide to maintenance bevacizumab on pharmacodynamic and clinical parameters among mCRC patients.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: Maintenance:BEVACIZUMAB

    Patients will be randomly assigned to receive induction chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab:

    • BEVACIZUMAB 5 mg/kg over 30 minutes, day 1
    • IRINOTECAN 165 mg/sqm IV over 1-h, day 1
    • OXALIPLATIN 85 mg/sqm IV over 2-h, day 1
    • L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1
    • 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1

    with cycles repeated every 2 weeks for 4 months (8 cycles), followed after 2 weeks by (if no progression occurs):

    - BEVACIZUMAB 7.5 mg/kg over 30 minutes, day 1 (every three weeks)

  • Drug: Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE

    Patients will be randomly assigned to receive induction chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab:

    • BEVACIZUMAB 5 mg/kg over 30 minutes, day 1
    • IRINOTECAN 165 mg/sqm IV over 1-h, day 1
    • OXALIPLATIN 85 mg/sqm IV over 2-h, day 1
    • L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1
    • 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1

    with cycles repeated every 2 weeks for 4 months (8 cycles), followed after 2 weeks by (if no progression occurs):

    • BEVACIZUMAB 7.5 mg/kg over 30 minutes, day 1 (every three weeks),
    • CAPECITABINE 500 mg/tid orally, continuously,
    • CYCLOPHOSPHAMIDE 50 mg/day orally, continuously.
Study Arms
  • Experimental: Maintenance:BEVACIZUMAB
    Induction: FOLFOXIRI; Manteinance: Bevacizumab
    Intervention: Drug: Maintenance:BEVACIZUMAB
  • Experimental: Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE
    Induction: FOLFOXIRI; Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE(Metronomic Chemotherapy)
    Intervention: Drug: Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2017)
232
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2014)
222
Actual Study Completion Date September 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically proven diagnosis of colorectal cancer.
  • Not resectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
  • At least one measurable lesion according to RECIST criteria.
  • Male or female of 18-75 years of age.
  • ECOG PS < 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years;
  • Life expectancy of at least 12 weeks.
  • Previous adjuvant chemotherapy containing oxaliplatin is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
  • Previous adjuvant chemotherapy with fluoropyrimidine monotherapy is allowed if more than 6 months have elapsed between the end of adjuvant and first relapse;
  • Neutrophils 1.5 x 109/L, Platelets 100 x 109/L, Hgb >9 g/dl.
  • Total bilirubin 1.5 time the upper-normal limits (UNL) of the institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) 2.5 x UNL, or 5 x UNL in case of liver metastases, alkaline phosphatase 2.5 x UNL, 5 x UNL in case of liver metastases.
  • Creatinine clearance >50 mL/min or serum creatinine 1.5 x UNL.
  • Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <1 g of protein/24 hr.
  • Written informed consent to treatment and translational analyses.

Exclusion Criteria:

  • Radiotherapy to any site within 4 weeks before the study.
  • Previous treatment with bevacizumab
  • Untreated brain metastases or spinal cord compression or primary brain tumours.
  • History or evidence upon physical examination of CNS disease unless adequately treated.
  • Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Evidence of bleeding diathesis or coagulopathy.
  • Uncontrolled hypertension.
  • Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
  • Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
  • Chronic, daily treatment with high-dose aspirin (>325 mg/day).
  • Treatment with any investigational drug within 30 days prior to enrollment.
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
  • Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
  • Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study (barrier contraceptive measure or oral contraception).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02271464
Other Study ID Numbers  ICMJE MOMA261111
2011-006332-23 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Alfredo Falcone, Azienda Ospedaliero, Universitaria Pisana
Study Sponsor  ICMJE Azienda Ospedaliero, Universitaria Pisana
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alfredo Falcone, MD Polo Oncologico Area Vasta Nord Ovest
PRS Account Azienda Ospedaliero, Universitaria Pisana
Verification Date December 2017

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