Metastatic Colorectal CancerPhase 3TRIBE2NCT02339116
Folfoxiri Plus Bev Followed by Reintroduction of Folfoxiri Plus Bev at Progression Versus Folfox Plus Bev Followed by Folfiri Plus Bev in mCRC
A Phase 3 study testing fluoruracil, Oxaliplatin and Irinotecan in people with Metastatic Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
Trial summary
Bev improves the efficacy of first-line chemotherapy in unresectable mCRC. In the phase III TRIBE trial upfront FOLFOXIRI plus bev provided a significant advantage in terms of PFS and RR compared to FOLFIRI plus bev. A trend toward better OS was also evidenced. The second-line treatment was at investigator's choice. 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?
- fluoruracil, Oxaliplatin and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 654 participants
- Where
- 1 siteItaly
- Study dates
- 26 Feb 2015to Feb 2021
- Phase
- Phase 3
- 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
Main Inclusion Criteria:
Histologically proven diagnosis of colorectal cancer Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease At least one measurable lesion according to RECIST1.1 criteria Availability of a tumoral sample Male or female of 18-75 years of age ECOG PS < or = 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years Life expectancy of at least 12 weeks Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months 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 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 (or <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 Will and ability to comply with the protocol Written informed consent to study procedures and to molecular analyses -
Main Exclusion Criteria:
Radiotherapy to any site within 4 weeks before the study Previous adjuvant oxaliplatin-containing chemotherapy 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 and prior histor of hypertensive crisis or hypertensive encephalopathy 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 Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment Any previous venous thromboembolism > NCI CTCAE Grade 3 History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
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 or 2 investigational agent half-lives (whichever is longer) Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: FIRST-LINE FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY REINTRODUCTION OF FOLFOXIRI PLUS BEVACIZUMAB AT PROGRESSION Versus FOLFOX PLUS BEVACIZUMAB FOLLOWED BY FOLFIRI PLUS BEVACIZUMAB AT PROGRESSION IN FIRST- AND SECOND-LINE TREATMENT OF UNRESECTABLE METASTATIC COLORECTAL CANCER.
Bev improves the efficacy of first-line chemotherapy in unresectable mCRC. In the phase III TRIBE trial upfront FOLFOXIRI plus bev provided a significant advantage in terms of PFS and RR compared to FOLFIRI plus bev. A trend toward better OS was also evidenced. The second-line treatment was at investigator's choice. A manageable increase in diarrhea, mucositis and neutropenia was reported, while no differences in febrile neutropenia, serious adverse events and toxic deaths were evidenced.
A growing amount of data support the clinical relevance of achieving an early and deep tumor shrinkage.
Read more
Phase III TML and BEBYP trials demonstrated that the continuation of bev beyond disease progression combined with a switched chemotherapy regimen provided a significant advantage in terms of OS and PFS.
Based on recent evidences, the partial interruption of the upfront "induction" chemotherapy before disease progression and the prosecution of bev until disease progression as maintenance treatment is a valid strategy in the treatment of mCRC.
On the basis of these considerations, a first-line doublet plus bev followed by a second-line switched doublet (from oxaliplatin to irinotecan and viceversa) plus bev should be considered a standard option for mCRC patients. Only retrospectively collected data are currently available about the efficacy of first-line FOLFOXIRI plus bev followed by second-line rechallenge with FOLFOXIRI plus bev. We therefore designed the present phase III randomized trial of first-line FOLFOXIRI plus bev followed by reintroduction of FOLFOXIRI plus bev at progression versus FOLFOX plus bev followed by FOLFIRI plus bev at progression in first- and second-line treatment of unresectable mCRC patients.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- fluoruracil, Oxaliplatin, Irinotecan, 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.
fluoruracilDrug
OxaliplatinDrug
IrinotecanDrug
BevacizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Folfoxiri/bev --> folfoxiri/bev | Experimental | FOLFOXIRI plus bev (to be repeated every 2 weeks for a maximum of 8 cycles):
Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Irinotecan 165 mg/sqm iv over 60 minutes, day 1 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1 At the time of disease progression, patients will re-introduce FOLFOXIRI plus bev at the same doses and schedule previously tolerated, for a maximum of 8 cycles. If no progression occurs during FOLFOXIRI plus bev, patients will receive maintenance 5-FU/LV plus bev at the same dose used in the last cycle of the induction treatment. Receives: Drug: fluoruracil; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Bevacizumab |
| folfox/bev-->folfiri/bev | Active comparator | mFOLFOX-6 plus bev (to be repeated every 2 weeks for a maximum of 8 cycles) Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluoruracil 400 mg/sqm iv bolus, day 1 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1
At the time of disease progression patients will receive FOLFIRI plus bev (to be repeated every 2 weeks for a maximum of 8 cycles):
Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Irinotecan 180 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluoruracil 400 mg/sqm iv bolus, day 1 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion. Receives: Drug: fluoruracil; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival 2 (PFS2)
PFS2 will be defined as beginning with randomization and ending with the first of the following events: a) death; b) disease progression on any treatment given after 1st progression. For patients that will not receive any treatment within 3 months after 1st progression, PFS2 will be equal to PFS. The determination of disease progression will be based on investigator-reported measurements. Disease status will be evaluated according to RECIST 1.1 criteria.
Censoring rules for PFS2 will be: end of study without PD, loss at follow-up. Curative surgery for metastasis will not result in censoring for PFS2.
Measured: from randomization to the first of the following events: a) death; b) disease progression on any treatment given after 1st progression, up to 18 months after last patient last visit
Secondary outcomes (6)
Progression free survival (PFS)
Progression free survival (PFS) is defined as the time from randomization to the 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 censored on the date of randomization
Measured: from randomization to to the first documentation of objective disease progression or death due to any cause, whichever occurs first, up to 18 months after last patient last visit
2nd-Progression free survival (2nd-PFS)
2nd-Progression free survival (2nd-PFS) is defined as the time from the beginning of the second-line treatment to the documentation of objective disease progression or death due to any cause, whichever occurs first. 2nd-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 2nd-progression free at the time of the analysis.
Measured: from the beginning of the second-line treatment to the documentation of objective disease progression or death due to any cause, whichever occurs first, up to 18 months after last patient last visit
Time to failure of strategy (TFS)
Time to failure of strategy (TFS) is defined as the time time from randomization to the first of the following events: death; patient requires the addition of a new therapeutic agent (i.e. an agent not included in the original strategy); patient experiences disease progression while being treated with all agents that are components of the initial treatment strategy (except for agents which cannot be used because of persistent toxicity or contraindications); or patient experiences disease progression during a partial or complete treatment holiday from initial treatment strategy and receives no further therapy within 3 months. Subjects who did not have an event as stated above while on study will be censored at the last evaluable radiographic assessment date.
Measured: from randomization to: death; patient requires a new therapeutic agent; PD on treatment with all agents of the initial strategy; PD during a partial or complete treatment holiday and receives no further therapy within 3 months, up to 18 months after LPLV
Overall survival (OS)
Overall survival (OS) 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: from randomization to the date of death due to any cause up to 18 months after last patient last visit
Objective Response Rate
percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the induction and the maintenance phases of treatment.
Measured: Every 8 weeks, up to 18 months after last patient last visit
Toxicity Rate
Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.
Measured: At every cycle of treatment up to the second evidence of PD or up to 18 months after LPLV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2015 (estimated)
- Study start26 Feb 2015
- Primary completion15 May 2017
- Study completionFeb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 654 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfredo Falcone, MD, Study director, Azienda Ospedaliero Universitaria Pisana, Pisa Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02339116
- Sponsor's protocol ID
- TRIBE2
- Acronym
- TRIBE2
- Status last verified
- Feb 2020
- First submitted
- 12 Jan 2015
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Stahler A, Modest DP, Stintzing S, Borelli B, Keller T, Held S, Fischer von Weikersthal L, Muller L, Graeven U, Decker T, Heintges T, Kahl C, Hoppe B, Kiani A, Kaiser F, Schwaner I, Fruehauf S, Karthaus M, Trarbach T, Klauschen F, Horst D, Cremolini C, Heinemann V. Individual Patient Data Meta-Analysis of Consensus Molecular Subtypes as Biomarkers of First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer. J Clin Oncol. 2026 Jan;44(1):31-41. doi: 10.1200/JCO-25-00596. Epub 2025 Nov 18.
PubMed 41252656Rossini D, Germani MM, Lonardi S, Pietrantonio F, Dell'Aquila E, Borelli B, Allegrini G, Maddalena G, Randon G, Marmorino F, Zaniboni A, Buonadonna A, Boccaccino A, Conca V, Antoniotti C, Passardi A, Masi G, Cremolini C. Treatments after second progression in metastatic colorectal cancer: A pooled analysis of the TRIBE and TRIBE2 studies. Eur J Cancer. 2022 Jul;170:64-72. doi: 10.1016/j.ejca.2022.04.019. Epub 2022 May 17.
PubMed 35594613Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
PubMed 32816630Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, Bordonaro R, Latiano TP, Tamburini E, Santini D, Passardi A, Marmorino F, Grande R, Aprile G, Zaniboni A, Murgioni S, Granetto C, Buonadonna A, Moretto R, Corallo S, Cordio S, Antonuzzo L, Tomasello G, Masi G, Ronzoni M, Di Donato S, Carlomagno C, Clavarezza M, Ritorto G, Mambrini A, Roselli M, Cupini S, Mammoliti S, Fenocchio E, Corgna E, Zagonel V, Fontanini G, Ugolini C, Boni L, Falcone A; GONO Foundation Investigators. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020 Apr;21(4):497-507. doi: 10.1016/S1470-2045(19)30862-9. Epub 2020 Mar 9.
PubMed 32164906Cremolini C, Marmorino F, Loupakis F, Masi G, Antoniotti C, Salvatore L, Schirripa M, Boni L, Zagonel V, Lonardi S, Aprile G, Tamburini E, Ricci V, Ronzoni M, Pietrantonio F, Valsuani C, Tomasello G, Passardi A, Allegrini G, Di Donato S, Santini D, Falcone A; all the investigators of the Gruppo Oncologico del Nord Ovest. TRIBE-2: a phase III, randomized, open-label, strategy trial in unresectable metastatic colorectal cancer patients by the GONO group. BMC Cancer. 2017 Jun 9;17(1):408. doi: 10.1186/s12885-017-3360-z.
PubMed 28599628
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FIRST-LINE FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY REINTRODUCTION OF FOLFOXIRI PLUS BEVACIZUMAB AT PROGRESSION Versus FOLFOX PLUS BEVACIZUMAB FOLLOWED BY FOLFIRI PLUS BEVACIZUMAB AT PROGRESSION IN FIRST- AND SECOND-LINE TREATMENT OF UNRESECTABLE METASTATIC COLORECTAL CANCER.
- ClinicalTrials.gov ID
- NCT02339116
- Acronym / sponsor ID
- TRIBE2 / TRIBE2
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 654 participants (estimated)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Study start
- 26 Feb 2015 (actual)
- Primary completion
- 15 May 2017 (actual)
- Study completion
- Feb 2021 (estimated)
- First posted
- 15 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bev improves the efficacy of first-line chemotherapy in unresectable mCRC. In the phase III TRIBE trial upfront FOLFOXIRI plus bev provided a significant advantage in terms of PFS and RR compared to FOLFIRI plus bev. A trend toward better OS was also evidenced. The second-line treatment was at investigator's choice. A manageable increase in diarrhea, mucositis and neutropenia was reported, while no differences in febrile neutropenia, serious adverse events and toxic deaths were evidenced.
A growing amount of data support the clinical relevance of achieving an early and deep tumor shrinkage.
Phase III TML and BEBYP trials demonstrated that the continuation of bev beyond disease progression combined with a switched chemotherapy regimen provided a significant advantage in terms of OS and PFS.
Based on recent evidences, the partial interruption of the upfront "induction" chemotherapy before disease progression and the prosecution of bev until disease progression as maintenance treatment is a valid strategy in the treatment of mCRC.
On the basis of these considerations, a first-line doublet plus bev followed by a second-line switched doublet (from oxaliplatin to irinotecan and viceversa) plus bev should be considered a standard option for mCRC patients. Only retrospectively collected data are currently available about the efficacy of first-line FOLFOXIRI plus bev followed by second-line rechallenge with FOLFOXIRI plus bev. We therefore designed the present phase III randomized trial of first-line FOLFOXIRI plus bev followed by reintroduction of FOLFOXIRI plus bev at progression versus FOLFOX plus bev followed by FOLFIRI plus bev at progression in first- and second-line treatment of unresectable mCRC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Folfoxiri/bev --> folfoxiri/bev | Experimental | Drug: fluoruracil, Drug: Oxaliplatin, Drug: Irinotecan, Drug: BevacizumabFOLFOXIRI plus bev (to be repeated every 2 weeks for a maximum of 8 cycles): Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Irinotecan 165 mg/sqm iv over 60 minutes, day 1 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1 At the time of disease progression, patients will re-introduce FOLFOXIRI plus bev at the same doses and schedule previously tolerated, for a maximum of 8 cycles. If no progression occurs during FOLFOXIRI plus bev, patients will receive maintenance 5-FU/LV plus bev at the same dose used in the last cycle of the induction treatment. |
| folfox/bev-->folfiri/bev | Active comparator | Drug: fluoruracil, Drug: Oxaliplatin, Drug: Irinotecan, Drug: BevacizumabmFOLFOX-6 plus bev (to be repeated every 2 weeks for a maximum of 8 cycles) Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluoruracil 400 mg/sqm iv bolus, day 1 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1 At the time of disease progression patients will receive FOLFIRI plus bev (to be repeated every 2 weeks for a maximum of 8 cycles): Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Irinotecan 180 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluoruracil 400 mg/sqm iv bolus, day 1 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fluoruracil | Drug | Folfoxiri/bev --> folfoxiri/bev, folfox/bev-->folfiri/bev |
| Oxaliplatin | Drug | Folfoxiri/bev --> folfoxiri/bev, folfox/bev-->folfiri/bev |
| Irinotecan | Drug | Folfoxiri/bev --> folfoxiri/bev, folfox/bev-->folfiri/bev |
| Bevacizumab | Drug | Folfoxiri/bev --> folfoxiri/bev, folfox/bev-->folfiri/bev |
Primary outcome
Progression Free Survival 2 (PFS2)
Time frame: from randomization to the first of the following events: a) death; b) disease progression on any treatment given after 1st progression, up to 18 months after last patient last visit
PFS2 will be defined as beginning with randomization and ending with the first of the following events: a) death; b) disease progression on any treatment given after 1st progression. For patients that will not receive any treatment within 3 months after 1st progression, PFS2 will be equal to PFS. The determination of disease progression will be based on investigator-reported measurements. Disease status will be evaluated according to RECIST 1.1 criteria. Censoring rules for PFS2 will be: end of study without PD, loss at follow-up. Curative surgery for metastasis will not result in censoring for PFS2.
6 secondary outcomes
Progression free survival (PFS)
Time frame: from randomization to to the first documentation of objective disease progression or death due to any cause, whichever occurs first, up to 18 months after last patient last visit
2nd-Progression free survival (2nd-PFS)
Time frame: from the beginning of the second-line treatment to the documentation of objective disease progression or death due to any cause, whichever occurs first, up to 18 months after last patient last visit
Time to failure of strategy (TFS)
Time frame: from randomization to: death; patient requires a new therapeutic agent; PD on treatment with all agents of the initial strategy; PD during a partial or complete treatment holiday and receives no further therapy within 3 months, up to 18 months after LPLV
Overall survival (OS)
Time frame: from randomization to the date of death due to any cause up to 18 months after last patient last visit
Objective Response Rate
Time frame: Every 8 weeks, up to 18 months after last patient last visit
Toxicity Rate
Time frame: At every cycle of treatment up to the second evidence of PD or up to 18 months after LPLV
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Derived from this study: PubMed 41252656Stahler A, Modest DP, Stintzing S, Borelli B, Keller T, Held S, Fischer von Weikersthal L, Muller L, Graeven U, Decker T, Heintges T, Kahl C, Hoppe B, Kiani A, Kaiser F, Schwaner I, Fruehauf S, Karthaus M, Trarbach T, Klauschen F, Horst D, Cremolini C, Heinemann V. Individual Patient Data Meta-Analysis of Consensus Molecular Subtypes as Biomarkers of First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer. J Clin Oncol. 2026 Jan;44(1):31-41. doi: 10.1200/JCO-25-00596. Epub 2025 Nov 18.
- Derived from this study: PubMed 35594613Rossini D, Germani MM, Lonardi S, Pietrantonio F, Dell'Aquila E, Borelli B, Allegrini G, Maddalena G, Randon G, Marmorino F, Zaniboni A, Buonadonna A, Boccaccino A, Conca V, Antoniotti C, Passardi A, Masi G, Cremolini C. Treatments after second progression in metastatic colorectal cancer: A pooled analysis of the TRIBE and TRIBE2 studies. Eur J Cancer. 2022 Jul;170:64-72. doi: 10.1016/j.ejca.2022.04.019. Epub 2022 May 17.
- Derived from this study: PubMed 32816630Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
- Derived from this study: PubMed 32164906Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, Bordonaro R, Latiano TP, Tamburini E, Santini D, Passardi A, Marmorino F, Grande R, Aprile G, Zaniboni A, Murgioni S, Granetto C, Buonadonna A, Moretto R, Corallo S, Cordio S, Antonuzzo L, Tomasello G, Masi G, Ronzoni M, Di Donato S, Carlomagno C, Clavarezza M, Ritorto G, Mambrini A, Roselli M, Cupini S, Mammoliti S, Fenocchio E, Corgna E, Zagonel V, Fontanini G, Ugolini C, Boni L, Falcone A; GONO Foundation Investigators. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020 Apr;21(4):497-507. doi: 10.1016/S1470-2045(19)30862-9. Epub 2020 Mar 9.
- Derived from this study: PubMed 28599628Cremolini C, Marmorino F, Loupakis F, Masi G, Antoniotti C, Salvatore L, Schirripa M, Boni L, Zagonel V, Lonardi S, Aprile G, Tamburini E, Ricci V, Ronzoni M, Pietrantonio F, Valsuani C, Tomasello G, Passardi A, Allegrini G, Di Donato S, Santini D, Falcone A; all the investigators of the Gruppo Oncologico del Nord Ovest. TRIBE-2: a phase III, randomized, open-label, strategy trial in unresectable metastatic colorectal cancer patients by the GONO group. BMC Cancer. 2017 Jun 9;17(1):408. doi: 10.1186/s12885-017-3360-z.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo Falcone, MD study director
Azienda Ospedaliero Universitaria Pisana, Pisa Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fluoruracil, Oxaliplatin and Irinotecan in people with Metastatic Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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 2 (PFS2) (time frame: from randomization to the first of the following events: a) death; b) disease progression on any treatment given after 1st progression, up to 18 months after last patient last visit). 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 NCT02339116, which also lists 5 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 5 Feb 2020.