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Metastatic Colorectal CancerPhase 2MOMANCT02271464

Maintenance Bevacizumab Only or Bevacizumab Plus Metronomic Chemotherapy in Advanced Colorectal Cancer

A Phase 2 study testing Maintenance:BEVACIZUMAB and Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE in people with Metastatic Colorectal Cancer, run by Azienda Ospedaliero, Universitaria Pisana at 20 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Maintenance:BEVACIZUMAB and Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE
Could I receive a placebo?
No, everyone receives an active treatment
How many people
232 participants
Where
20 sitesItaly
Study dates
Mar 2012to Sep 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Italy20 sites

  • Istituto Ospedaliero Fondazione Poliambulanza Di Brescia

    Brescia, 25124

  • Pres.Ospedaliero Spedali Civili Brescia

    Brescia, 25125

  • Istituti Ospitalieri Di Cremona

    Cremona, 26100

  • Azienda Ospedaliera S. Croce E Carle Di Cuneo

    Cuneo, 12100

  • A.O. Universitaria Arcispedale S.Anna Di Ferrara

    Ferrara, 44100

  • Ausl Di Frosinone -

    Frosinone, 03100

  • E.O. Ospedali Galliera

    Genova, 16128

  • Ospedale Per Acuti Mater Salutis Di Legnago

    Legnago, 37045

  • Oncologia AUSL 2 Lucca

    Lucca

  • Irccs Fondazione Centro S. Raffaele Del Monte Tabor

    Milan, 20132

  • A.O. Universitaria Federico Ii Di Napoli

    Naples, 80131

  • Irccs Istituto Oncologico Veneto (Iov)

    Padova, 35128

  • Polo Oncologico Area Vasta Nord Ovest

    Pisa, 56100

  • Ausl 5 Di Pisa

    Pontedera, 56100

  • Ospedale Mesericordia E Dolce

    Prato, 59100

  • Ospedale S. Maria Nuova

    Reggio Emilia, 42100

  • Ospedale San Giovanni Calibita Fatebenefratelli

    Roma, 00186

  • Ospedale San Pietro Fatebenefratelli Di Roma

    Roma, 00189

  • Campus Biomedico

    Roma

  • A.O. Universitaria S. Maria Della Misericordia

    Udine, 33100

Other trials in Italy

About this study

Official title: 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

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.

Being tested
Maintenance:BEVACIZUMAB, Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE
Keywords
Metastatic colorectal cancer, Ist line therapy, metronimic therapy, bevacizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Maintenance:BEVACIZUMABDrug

    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)

  • Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDEDrug

    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 groups in NCT02271464
Study groupRoleWhat they receive
Maintenance:BEVACIZUMABExperimentalInduction: FOLFOXIRI; Manteinance: Bevacizumab
Receives: Drug: Maintenance:BEVACIZUMAB
Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDEExperimentalInduction: FOLFOXIRI; Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE(Metronomic Chemotherapy)
Receives: Drug: Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. progression-free survival (PFS)

    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.

    Measured: up to 4 years

Secondary outcomes (8)

  1. Best overall response rate (ORR)

    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.

    Measured: up to 4 years

  2. Duration of response

    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

    Measured: up to 4 years

  3. Resection rate

    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.

    Measured: up to 4 years

  4. Time to strategy failure (TSF)

    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.

    Measured: up to 4 years

  5. Time to 2nd progressive disease

    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.

    Measured: up to 4 years

  6. Overall survival (OS)

    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.

    Measured: up to 4 years

  7. Toxicity rate

    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.

    Measured: up to 4 years

  8. Overall toxicity rate

    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.

    Measured: up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2014 (estimated)
  2. Study startMar 2012
  3. Primary completionMar 2017
  4. Study completionSep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
232 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02271464
Sponsor's protocol ID
MOMA261111
Other IDs
2011-006332-23
Acronym
MOMA
Status last verified
Dec 2017
First submitted
20 Oct 2014
Last updated
7 Dec 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Cremolini C, Marmorino F, Bergamo F, Aprile G, Salvatore L, Masi G, Dell'Aquila E, Antoniotti C, Murgioni S, Allegrini G, Borelli B, Gemma D, Casagrande M, Granetto C, Delfanti S, Di Donato S, Schirripa M, Sensi E, Tonini G, Lonardi S, Fontanini G, Boni L, Falcone A. Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial. Eur J Cancer. 2019 Mar;109:175-182. doi: 10.1016/j.ejca.2018.12.028. Epub 2019 Feb 5.

    PubMed 30735919

  • van Dijk E, Biesma HD, Cordes M, Smeets D, Neerincx M, Das S, Eijk PP, Murphy V, Barat A, Bacon O, Prehn JHM, Betge J, Gaiser T, Fender B, Meijer GA, McNamara DA, Klinger R, Koopman M, Ebert MPA, Kay EW, Hennessey BT, Verheul HMW, Gallagher WM, O'Connor DP, Punt CJA, Loupakis F, Lambrechts D, Byrne AT, van Grieken NCT, Ylstra B. Loss of Chromosome 18q11.2-q12.1 Is Predictive for Survival in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab. J Clin Oncol. 2018 Jul 10;36(20):2052-2060. doi: 10.1200/JCO.2017.77.1782. Epub 2018 May 24.

    PubMed 29792754

  • Cremolini C, Casagrande M, Loupakis F, Aprile G, Bergamo F, Masi G, Moretto R R, Pietrantonio F, Marmorino F, Zucchelli G, Tomasello G, Tonini G, Allegrini G, Granetto C, Ferrari L, Urbani L, Cillo U, Pilati P, Sensi E, Pellegrinelli A, Milione M, Fontanini G, Falcone A. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017 Mar;73:74-84. doi: 10.1016/j.ejca.2016.10.028. Epub 2016 Dec 13.

    PubMed 27986363

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Maintenance:BEVACIZUMAB and Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE in people with Metastatic Colorectal Cancer, run by Azienda Ospedaliero, Universitaria Pisana at 20 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression-free survival (PFS) (time frame: up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02271464, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2017.

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