NCT02271464

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
232

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Mar 2012

Longer than P75 for phase_2

Geographic Reach
1 country

20 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2012

Completed
2.6 years until next milestone

First Submitted

Initial submission to the registry

October 20, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 22, 2014

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2017

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2017

Completed
Last Updated

December 7, 2017

Status Verified

December 1, 2017

Enrollment Period

5 years

First QC Date

October 20, 2014

Last Update Submit

December 5, 2017

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic colorectal cancerIst line therapymetronimic therapybevacizumab

Outcome Measures

Primary Outcomes (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.

    up to 4 years

Secondary Outcomes (8)

  • Best overall response rate (ORR)

    up to 4 years

  • Duration of response

    up to 4 years

  • Resection rate

    up to 4 years

  • Time to strategy failure (TSF)

    up to 4 years

  • Time to 2nd progressive disease

    up to 4 years

  • +3 more secondary outcomes

Study Arms (2)

Maintenance:BEVACIZUMAB

EXPERIMENTAL

Induction: FOLFOXIRI; Manteinance: Bevacizumab

Drug: Maintenance:BEVACIZUMAB

Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE

EXPERIMENTAL

Induction: FOLFOXIRI; Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE(Metronomic Chemotherapy)

Drug: Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE

Interventions

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
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.

Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Istituto Ospedaliero Fondazione Poliambulanza Di Brescia

Brescia, 25124, Italy

Location

Pres.Ospedaliero Spedali Civili Brescia

Brescia, 25125, Italy

Location

Istituti Ospitalieri Di Cremona

Cremona, 26100, Italy

Location

Azienda Ospedaliera S. Croce E Carle Di Cuneo

Cuneo, 12100, Italy

Location

A.O. Universitaria Arcispedale S.Anna Di Ferrara

Ferrara, 44100, Italy

Location

Ausl Di Frosinone -

Frosinone, 03100, Italy

Location

E.O. Ospedali Galliera

Genova, 16128, Italy

Location

Ospedale Per Acuti Mater Salutis Di Legnago

Legnago, 37045, Italy

Location

Oncologia AUSL 2 Lucca

Lucca, Italy

Location

Irccs Fondazione Centro S. Raffaele Del Monte Tabor

Milan, 20132, Italy

Location

A.O. Universitaria Federico Ii Di Napoli

Napoli, 80131, Italy

Location

Irccs Istituto Oncologico Veneto (Iov)

Padua, 35128, Italy

Location

Polo Oncologico Area Vasta Nord Ovest

Pisa, 56100, Italy

Location

Ausl 5 Di Pisa

Pontedera, 56100, Italy

Location

Ospedale Mesericordia E Dolce

Prato, 59100, Italy

Location

Ospedale S. Maria Nuova

Reggio Emilia, 42100, Italy

Location

Ospedale San Giovanni Calibita Fatebenefratelli

Roma, 00186, Italy

Location

Ospedale San Pietro Fatebenefratelli Di Roma

Roma, 00189, Italy

Location

Campus Biomedico

Roma, Italy

Location

A.O. Universitaria S. Maria Della Misericordia

Udine, 33100, Italy

Location

Related Publications (3)

  • 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.

    PMID: 30735919DERIVED

  • 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.

    PMID: 29792754DERIVED

  • 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.

    PMID: 27986363DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Study Officials

  • Alfredo Falcone, MD

    Polo Oncologico Area Vasta Nord Ovest

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

October 20, 2014

First Posted

October 22, 2014

Study Start

March 1, 2012

Primary Completion

March 1, 2017

Study Completion

September 1, 2017

Last Updated

December 7, 2017

Record last verified: 2017-12

Locations

IT(20)