Metastatic Colorectal CancerPhase 3TRIPLETENCT03231722
First Line mFOLFOXIRI + PANITUMUMAB vs mFOLFOX + PANITUMUMAB IN RAS AND BRAF WT METASTATIC COLORECTAL CANCER PATIENTS
A Phase 3 study testing Panitumumab, Irinotecan and Oxaliplatin in people with Metastatic Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 4 sites in Italy.
Trial summary
The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients. The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic acid, oxaliplatin and irinotecan) plus bev… 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?
- Panitumumab, Irinotecan and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 435 participants
- Where
- 4 sitesItaly
- Study dates
- 13 Sep 2017to 24 Jun 2022
- 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
Who may be able to join
- Written informed consent to study procedures and to molecular analyses.
- 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 RECIST 1.1.
- Availability of a tumour tissue sample (primary tumour and/or metastatic sites).
- Male or female of 18-75 years of age
Show all 19Show fewer
- ECOG PS ≤2 for patients aged ≤70 years; ECOG PS 0 for patients aged 71 to 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.
- RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of primary colorectal cancer or related metastasis (local or central laboratory assessment).
- Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥9 g/dl.
- Total bilirubin ≤ 1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in the 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.
- Male subjects with female partners of childbearing potential must be willing to use adequate contraception - Contraception, starting with the first dose of study therapy through 180 days after the last dose of treatment.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit
- Female subjects of childbearing potential must be willing to use an adequate method of contraception - Contraception, for the course of the study starting with the first dose of study therapy through 180 days after the last dose of treatment.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Will and ability to comply with the protocol.
Who cannot join
- Previous treatment for metastatic disease.
- Radiotherapy to any site within 4 weeks before the study.
- Previous adjuvant oxaliplatin-containing chemotherapy.
- Previous treatment with EGFR inhibitors.
- Untreated brain metastases or spinal cord compression or primary brain tumours.
- History or evidence upon physical examination of CNS disease unless adequately treated.
Show all 21Show fewer
- Symptomatic peripheral neuropathy > 1 grade NCIC-CTG criteria.
- Creatinine clearance < 50 mL/min or serum creatinine >1.5 x UNL.
- Clinical signs of malnutrition.
- Neutrophils <1.5 x 109/L, Platelets <100 x 109/L, Hgb <9 g/dl.
- Diagnosis of interstitial pneumonitis or pulmonary fibrosis.
- Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
- Clinically significant (e.g. 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 (CHF), serious cardiac arrhythmia requiring medication.
- Treatment with any investigational drug within 30 days prior to enrolment 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.
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness, or hepatitis B or C.
- Definite contraindications for the use of corticosteroids and antihistamines as premedication.
- History of severe allergic reactions or hypersensitivity to trial drugs or any of their excipients.
- Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
- 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 and until 180 days after the last trial treatment.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Fondazione IRCCS Istituto Nazionale Tumori
Milan, 20133
Fondazione IRCCS Istituto Oncologico Veneto
Padova, 35128
A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
Pisa, 56126
Azienda Ospedaliera Universitaria Integrata Verona
Verona, 37126
About this study
Official title: The TRIPLETE Study RANDOMIZED PHASE III STUDY OF TRIPLET mFOLFOXIRI PLUS PANITUMUMAB Versus mFOLFOX6 PLUS PANITUMUMAB AS INITIAL THERAPY FOR UNRESECTABLE RAS AND BRAF WILDTYPE METASTATIC COLORECTAL CANCER PATIENTS
- The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients.
- The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic acid, oxaliplatin and irinotecan) plus bev significantly prolongs PFS and OS and increases RECIST response rate, ETS and DoR, as compared to FOLFIRI (5-fluoruracil folinic acid, and irinotecan) plus bev. The advantage provided by the intensification of the upfront chemotherapy backbone is independent of RAS and BRAF mutational status.
- Some phase II trials recently assessed the safety and activity of the combination of three-drugs chemotherapy regimens with an anti-EGFR monoclonal antibody. Promising activity results in terms of RECIST response rate and R0 resection rate have been achieved, with some safety concerns with special regards to gastrointestinal toxicity.
- In the phase II randomized MACBETH study the combination of a modified schedule of FOLFOXIRI with cetuximab determined remarkable activity results, with an acceptable and manageable safety profile.
- The optimal duration of the upfront treatment with chemotherapy plus anti-EGFRs is not established. The phase II MACRO-2 trial suggested that interrupting FOLFOX after 4 months while continuing cet alone as maintenance, is a reasonable option.
- Activity parameters (RECIST response rate, ETS, DoR) are clinically relevant endpoints, associated with longer survival, in particular with anti-EGFR moAb-based treatment.
On the basis of these considerations, we designed the present phase III randomized trial of first-line mFOLFOXIRI plus pan versus mFOLFOX6 plus pan in RAS and BRAF wt unresectable mCRC patients.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Panitumumab, Irinotecan, Oxaliplatin, l-leucovorin, 5-fluorouracil
- Keywords
- mFOLFOXIRI + Panitumumab, RAS and BRAF wt
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
6 mg/kg iv over 60 minutes, day 1
IrinotecanDrug
150 mg/sqm iv over 60 minutes day 1
OxaliplatinDrug
85 mg/sqm iv over 2 hours day 1
l-leucovorinDrug
200 mg/sqm iv over 2 hours
5-fluorouracilDrug
400 mg/sqm iv bolus, day 1 followed by 2400 mg/sqm 48 h-continuous infusion, starting on day 1;
| Study group | Role | What they receive |
|---|---|---|
| mFOLFOX6 + Panitumab | Active comparator | * Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by
* Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with
* L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by
* 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by
* 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice. Receives: Drug: Panitumumab; Drug: Irinotecan; Drug: l-leucovorin; Drug: 5-fluorouracil |
| mFOLFOXIRI + Panitumumab | Experimental | * Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by
* Irinotecan 150 mg/sqm iv over 60 minutes day 1, followed by
* Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with
* L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by
* 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice. Receives: Drug: Panitumumab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: l-leucovorin; Drug: 5-fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria
Measured: 12 months
Secondary outcomes (8)
Overall Toxicity Rate
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)
Measured: 24 months
Toxicity Rate
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)
Measured: 24 months
Progression Free Survival
the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. Documentation of disease progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment
Measured: 24 months
Overall Survival
the time from randomization to the date of death due to any cause
Measured: 48 months
Centrally assessed Overall response rate
the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria based on central re-evaluation of CT scan images.
Measured: 12 months
Early Tumour Shrinkage Rate
the percentage of patients, relative to the total of the enrolled subjects, achieving a ≥20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline.
Measured: up to 2 months from randomization
Deepness of Response
the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline.
Measured: 12 months
R0 Resection Rate
the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2017
- Study start13 Sep 2017
- Primary completion15 Jun 2022
- Study completion24 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- 435 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chiara Cremolini, MD, PhD, Study chair, U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - Università di Pisa Istituto Toscano Tumori
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03231722
- Sponsor's protocol ID
- TRIPLETE
- Acronym
- TRIPLETE
- Status last verified
- Jan 2023
- First submitted
- 3 Jul 2017
- Last updated
- 5 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Conca V, Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Randon G, Lavacchi D, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Fazio R, Murgioni S, Borelli B, Buonadonna A, Germani MM, Formica V, Carullo M, Bordonaro R, Aprile G, Zaniboni A, Masi G, Boni L, Cremolini C. Upfront Modified FOLFOXIRI Plus Panitumumab for RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Results of the Phase III TRIPLETE Study. J Clin Oncol. 2026 Feb 10;44(5):361-369. doi: 10.1200/JCO-25-01337. Epub 2026 Jan 8.
PubMed 41505697Sposito C, Pietrantonio F, Maspero M, Di Benedetto F, Vivarelli M, Tisone G, De Carlis L, Romagnoli R, Gruttadauria S, Colledan M, Agnes S, Ettorre G, Baccarani U, Torzilli G, Di Sandro S, Pinelli D, Caccamo L, Sartore Bianchi A, Spreafico C, Torri V, Mazzaferro V. Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial). Clin Colorectal Cancer. 2023 Jun;22(2):250-255. doi: 10.1016/j.clcc.2023.01.003. Epub 2023 Feb 3.
PubMed 36822922Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Boccaccino A, Morano F, Brugia M, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Randon G, Murgioni S, Borelli B, Buonadonna A, Giordano M, Fontanini G, Conca V, Formica V, Aglietta M, Bordonaro R, Aprile G, Masi G, Boni L, Cremolini C. Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO. J Clin Oncol. 2022 Sep 1;40(25):2878-2888. doi: 10.1200/JCO.22.00839. Epub 2022 Jun 6.
PubMed 35666229Borelli B, Moretto R, Lonardi S, Bonetti A, Antoniotti C, Pietrantonio F, Masi G, Burgio V, Marmorino F, Salvatore L, Rossini D, Zaniboni A, Zucchelli G, Martignetti A, Di Battista M, Pella N, Passardi A, Boccaccino A, Leone F, Colombo C, Granetto C, Vannini F, Marsico VA, Martinelli E, Antonuzzo L, Vitello S, Delliponti L, Boni L, Cremolini C, Falcone A. TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer. ESMO Open. 2018 Jul 9;3(4):e000403. doi: 10.1136/esmoopen-2018-000403. eCollection 2018.
PubMed 30018814
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The TRIPLETE Study RANDOMIZED PHASE III STUDY OF TRIPLET mFOLFOXIRI PLUS PANITUMUMAB Versus mFOLFOX6 PLUS PANITUMUMAB AS INITIAL THERAPY FOR UNRESECTABLE RAS AND BRAF WILDTYPE METASTATIC COLORECTAL CANCER PATIENTS
- ClinicalTrials.gov ID
- NCT03231722
- Acronym / sponsor ID
- TRIPLETE / TRIPLETE
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- mFOLFOXIRI + Panitumumab, RAS and BRAF wt
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 435 participants (actual)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Study start
- 13 Sep 2017 (actual)
- Primary completion
- 15 Jun 2022 (actual)
- Study completion
- 24 Jun 2022 (actual)
- First posted
- 27 Jul 2017 (actual)
- 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.
- The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients.
- The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic acid, oxaliplatin and irinotecan) plus bev significantly prolongs PFS and OS and increases RECIST response rate, ETS and DoR, as compared to FOLFIRI (5-fluoruracil folinic acid, and irinotecan) plus bev. The advantage provided by the intensification of the upfront chemotherapy backbone is independent of RAS and BRAF mutational status.
- Some phase II trials recently assessed the safety and activity of the combination of three-drugs chemotherapy regimens with an anti-EGFR monoclonal antibody. Promising activity results in terms of RECIST response rate and R0 resection rate have been achieved, with some safety concerns with special regards to gastrointestinal toxicity.
- In the phase II randomized MACBETH study the combination of a modified schedule of FOLFOXIRI with cetuximab determined remarkable activity results, with an acceptable and manageable safety profile.
- The optimal duration of the upfront treatment with chemotherapy plus anti-EGFRs is not established. The phase II MACRO-2 trial suggested that interrupting FOLFOX after 4 months while continuing cet alone as maintenance, is a reasonable option.
- Activity parameters (RECIST response rate, ETS, DoR) are clinically relevant endpoints, associated with longer survival, in particular with anti-EGFR moAb-based treatment.
On the basis of these considerations, we designed the present phase III randomized trial of first-line mFOLFOXIRI plus pan versus mFOLFOX6 plus pan in RAS and BRAF wt 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 |
|---|---|---|
| mFOLFOX6 + Panitumab | Active comparator | Drug: Panitumumab, Drug: Irinotecan, Drug: l-leucovorin, Drug: 5-fluorouracil* Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by * Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by * 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice. |
| mFOLFOXIRI + Panitumumab | Experimental | Drug: Panitumumab, Drug: Irinotecan, Drug: Oxaliplatin, Drug: l-leucovorin, Drug: 5-fluorouracil* Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by * Irinotecan 150 mg/sqm iv over 60 minutes day 1, followed by * Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Written informed consent to study procedures and to molecular analyses.
- 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 RECIST 1.1.
- Availability of a tumour tissue sample (primary tumour and/or metastatic sites).
Key exclusion criteria (21 listed)
- Previous treatment for metastatic disease.
- Radiotherapy to any site within 4 weeks before the study.
- Previous adjuvant oxaliplatin-containing chemotherapy.
- Previous treatment with EGFR inhibitors.
- Untreated brain metastases or spinal cord compression or primary brain tumours.
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 |
|---|---|---|
| Panitumumab6 mg/kg iv over 60 minutes, day 1 | Drug | mFOLFOX6 + Panitumab, mFOLFOXIRI + Panitumumab |
| Irinotecan150 mg/sqm iv over 60 minutes day 1 | Drug | mFOLFOX6 + Panitumab, mFOLFOXIRI + Panitumumab |
| Oxaliplatin85 mg/sqm iv over 2 hours day 1 | Drug | mFOLFOXIRI + Panitumumab |
| l-leucovorin200 mg/sqm iv over 2 hours | Drug | mFOLFOX6 + Panitumab, mFOLFOXIRI + Panitumumab |
| 5-fluorouracil400 mg/sqm iv bolus, day 1 followed by 2400 mg/sqm 48 h-continuous infusion, starting on day 1; | Drug | mFOLFOX6 + Panitumab, mFOLFOXIRI + Panitumumab |
Primary outcome
Overall response rate
Time frame: 12 months
the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria
8 secondary outcomes
Overall Toxicity Rate
Time frame: 24 months
Toxicity Rate
Time frame: 24 months
Progression Free Survival
Time frame: 24 months
Overall Survival
Time frame: 48 months
Centrally assessed Overall response rate
Time frame: 12 months
Early Tumour Shrinkage Rate
Time frame: up to 2 months from randomization
Deepness of Response
Time frame: 12 months
R0 Resection Rate
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2023.
- Derived from this study: PubMed 41505697Conca V, Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Randon G, Lavacchi D, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Fazio R, Murgioni S, Borelli B, Buonadonna A, Germani MM, Formica V, Carullo M, Bordonaro R, Aprile G, Zaniboni A, Masi G, Boni L, Cremolini C. Upfront Modified FOLFOXIRI Plus Panitumumab for RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Results of the Phase III TRIPLETE Study. J Clin Oncol. 2026 Feb 10;44(5):361-369. doi: 10.1200/JCO-25-01337. Epub 2026 Jan 8.
- Derived from this study: PubMed 36822922Sposito C, Pietrantonio F, Maspero M, Di Benedetto F, Vivarelli M, Tisone G, De Carlis L, Romagnoli R, Gruttadauria S, Colledan M, Agnes S, Ettorre G, Baccarani U, Torzilli G, Di Sandro S, Pinelli D, Caccamo L, Sartore Bianchi A, Spreafico C, Torri V, Mazzaferro V. Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial). Clin Colorectal Cancer. 2023 Jun;22(2):250-255. doi: 10.1016/j.clcc.2023.01.003. Epub 2023 Feb 3.
- Derived from this study: PubMed 35666229Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Boccaccino A, Morano F, Brugia M, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Randon G, Murgioni S, Borelli B, Buonadonna A, Giordano M, Fontanini G, Conca V, Formica V, Aglietta M, Bordonaro R, Aprile G, Masi G, Boni L, Cremolini C. Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO. J Clin Oncol. 2022 Sep 1;40(25):2878-2888. doi: 10.1200/JCO.22.00839. Epub 2022 Jun 6.
- Derived from this study: PubMed 30018814Borelli B, Moretto R, Lonardi S, Bonetti A, Antoniotti C, Pietrantonio F, Masi G, Burgio V, Marmorino F, Salvatore L, Rossini D, Zaniboni A, Zucchelli G, Martignetti A, Di Battista M, Pella N, Passardi A, Boccaccino A, Leone F, Colombo C, Granetto C, Vannini F, Marsico VA, Martinelli E, Antonuzzo L, Vitello S, Delliponti L, Boni L, Cremolini C, Falcone A. TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer. ESMO Open. 2018 Jul 9;3(4):e000403. doi: 10.1136/esmoopen-2018-000403. eCollection 2018.
- Individual participant dataSharing planned: No
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CRC
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.
Chiara Cremolini, MD, PhD study chair
U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - Università di Pisa Istituto Toscano Tumori
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Panitumumab, Irinotecan and Oxaliplatin in people with Metastatic Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 4 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 19 inclusion and 21 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 5 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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?
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?
Overall response rate (time frame: 12 months). 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 NCT03231722, which also lists 4 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 Jan 2023.