Metastatic Colorectal CancerPhase 3COMETSNCT01030042
Trial Comparing Two Two Sequences of Therapy in Colorectal Metastatic Patients
A Phase 3 study testing FOLFOX-4 and Irinotecan/Cetuximab in people with Metastatic Colorectal Cancer, run by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente at 32 sites in Italy.
Trial summary
Primary Objectives: Aim of this study is to compare the efficacy and safety of two different sequences of chemotherapeutic agents in order to optimize the treatment of patients with metastatic colorectal cancer progressed to a first line chemotherapy with FOLFIRI and bevacizumab. 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?
- FOLFOX-4 and Irinotecan/Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 32 sitesItaly
- Study dates
- Sep 2009to Jun 2015
- 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
- Age >18 <75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- Performance Status (ECOG-PS) 0-1 at study entry
- Neutrophils ≥ 1.5 x 1039/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL
- Bilirubin level either normal or < 1.5 x upper limit of normal (ULN)
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- Asparagine aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 X ULN (≤ 5 x ULN if liver metastasis are present)
- Serum creatinine < 1.5 x ULN
- Effective contraception for both male and female patients
- Life expectancy of ≥ 3 months
- Signed written informed consent
Who cannot join
- History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
- Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
- History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake
- Known grade 3 or 4 allergic reaction to any of the components of the treatment
- Known drug abuse/ alcohol abuse
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
Italy32 sites
A.O. Ospedale Umberto I - Università - Località Torretta
Ancona, Ancona, 60020
Ospedali Riuniti, Largo Barozzi, 1
Bergamo, Bergamo, 24128
Fondazione Poliambulanza, Via Bissolati 57
Brescia, Brescia, 25100
Spedali Civili
Brescia, BS, 25100
Università degli Studi
Candiolo, TO, 10060
Istituto Oncologico del Mediterraneo
Catania, CT, 95029
A.O. Ospedale S.Anna
Como, Italy, 22100
ASL 11
Empoli, FI, 50010
Ospedale Profili
Fabriano, AN, 60044
Usl 11 Ospedale Murri
Fermo, AP, 63023
Università
Florence, FI, 50139
Ospedale Serbelloni
Gorgonzola, MI, 20064
AUSL di Lanciano-Vasto
Lanciano, CH, 66034
Ospedale Mater Salutis
Legnago, VR, 37045
Ospedale Maggiore
Lodi, LO, 26900
A.O. Carlo Poma - Via Albertoni, 1
Mantua, Mantova, 46100
Istituto di Ricerca S.Raffaele
Milan, MI, 20100
Ospedale Fatebenefratelli
Milan, MI, 20100
A.O. S.Gerardo
Monza, MI, 20052
Istituto Tumori - Fondazione Pascale
Naples, 80131
Istituto Oncologico Veneto
Padova, PD, 35124
A.O. S.Salvatore
Pesaro, PS, 61100
Azienda Ospedaliera San Carlo
Potenza, PZ, 85100
Università Policlinico Umberto I
Roma, RM, 00186
Ospedale Sant'Andrea
Roma, RM, 00189
Università Campus Biomedico, Via Emilio Longoni, 83
Roma, Roma, 00155
A.O. S.Giovanni Calabita Fatebenefratelli
Roma, Roma, 00186
AULSS 18 di Rovigo
Rovigo, RO, 45100
Ospedale Morelli
Sondalo, SO, 23100
Ospedale S.Vincenzo
Taormina, ME, 98039
A.O. Treviglio-Caravaggio, P.le Ospedale n1
Treviglio, Bergamo, 24047
Ospedale Civile
Urbino, PS, 61029
About this study
Official title: Randomized, Phase III, Multicenter Trial Comparing Two Different Sequences of therapyFOLFOX-4 vs FOLFOX-4 Followed by Irinotecan/Cetuximab in Metastatic Colorectal Patients Treated With FOLFIRI /Bevacizumab as First Line Chemotherapy
Primary Objectives:
Aim of this study is to compare the efficacy and safety of two different sequences of chemotherapeutic agents in order to optimize the treatment of patients with metastatic colorectal cancer progressed to a first line chemotherapy with FOLFIRI and bevacizumab. Primary endpoint will be overall survival, defined as the time elapsed from the date of randomization to the date of patient death due to any cause, or the last date the patient was known to be alive.
Read more
Secondary Objectives Progression free survival, Quality of life, Health resource utilisation and economic evaluation, Toxicity and incidence of adverse events
The study regimen includes:
Strategy A: FOLFOX-4 followed, after progression, by irinotecan/cetuximab Strategy B: irinotecan/cetuximab followed, after progression, by FOLFOX-4 Patients will be randomly assigned to one of the two treatment sequences (with 1:1 ratio) using a block design randomization procedure stratified according to center.
The patient accrual period is planned for approximately 36 months. To assess OS, all pts will be followed for up to 18 months after the last patient is randomised. The maximum estimated study duration is approximately 54 months.All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.
Read the detailed description
Target population:
Patients with histologically confirmed metastatic colorectal cancer progressed after a first line treatment containing FOLFIRI and BEV
Inclusion criteria:
- Age >18 < 75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- ECOG performance status 0-1 at study entry
Endpoints:
- Response Rate, Disease control rate, The duration of overall response, Overall survival, PFS, Time to treatment failure, Quality of Life, Incidence of AEs, Frequency and nature of serious adverse reactions (SADRs), Premature withdrawals
Statistical methods:
Assuming a randomization ratio of 1:1, 282 deaths are required in order to achieve a power of 80% of detecting a hazard ratio of 0.72 in favour of one of the two sequences, translating in an increase of median survival time from 10 to 14 months, with a type I error of 5%, two-sided, using the Mantel-Cox version of the log-rank test. With a uniform accrual period of 3 years and a follow-up of 18 months, about 350 patients will be needed to reach the target number of events.
All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.
All OS and PFS curves will be drawn with the Kaplan-Meier method. Results will be presented as Hazard Ratio (HRs) and their 95% Confidence Interval (CIs).
On annual basis, starting from the second year, an interim analysis will be conducted. In principle, no formal stopping rule will be applied, unless otherwise suggested by the DSMC. Safety reports will be drawn on annual basis.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- FOLFOX-4, Irinotecan/Cetuximab
- Keywords
- metastatic, colorectal cancer, two sequences therapy
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOX-4Drug
Also called Oxaliplatin, 5FU, Leucovorin
Day 1: OXA will be administered as a 85 mg/m2 iv infusion over 2 hours; Leucovorin as a 100 mg/m2 infusion over 2 hours, 5-FU will be given as a 400 mg/m2 bolus injection, and then as a 600 mg/m2 continuous infusion over 22 hours after the first infusion Day 2: Leucovorin 100 mg/m2 (alone), followed by 5-FU 400 mg/m2 bolus injection, and 5-FU 600 mg/m2 continuous infusion after the first infusion Cycle length is 2 weeks comprising approximately 48 hours of infusion and 12 days of rest. Cycles are to be repeated every second week for a total of either 6 (12 weeks) or 12 cycles (24 weeks).
Irinotecan/CetuximabDrug
Also called CPT11/Cetuximab
CET 400 mg/m2 intravenously via infusion pump given over a 120 min time and weekly CET infusions at a maintenance dose of 250 mg/m2 given over a 60 min time.
IRI 180 mg/m2 iv infusion over 30-90 min. Cycle length is 2 weeks and it is to be repeated until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab/Irinotecan | Experimental | Cetuximab/irinotecan followed, after progression, by FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil) Receives: Drug: Irinotecan/Cetuximab |
| FOLFOX 4 | Active comparator | FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil) followed, after progression, by irinotecan/cetuximab Receives: Drug: FOLFOX-4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measured: the time from the date of randomisation to the date of death
Secondary outcomes (1)
Progression free survival
Measured: the time relapsed from the date of randomization and the date of progression after third-line treatment or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2009 (estimated)
- Study startSep 2009
- Primary completionApr 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01030042
- Sponsor's protocol ID
- 2007-006254-26
- Acronym
- COMETS
- Status last verified
- Dec 2009
- First submitted
- 9 Dec 2009
- Last updated
- 15 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Phase III, Multicenter Trial Comparing Two Different Sequences of therapyFOLFOX-4 vs FOLFOX-4 Followed by Irinotecan/Cetuximab in Metastatic Colorectal Patients Treated With FOLFIRI /Bevacizumab as First Line Chemotherapy
- ClinicalTrials.gov ID
- NCT01030042
- Acronym / sponsor ID
- COMETS / 2007-006254-26
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- metastatic, colorectal cancer, two sequences therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Gruppo Italiano per lo studio dei Carcinomi dell'Apparato DigerenteUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Apr 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 10 Dec 2009 (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.
Primary Objectives:
Aim of this study is to compare the efficacy and safety of two different sequences of chemotherapeutic agents in order to optimize the treatment of patients with metastatic colorectal cancer progressed to a first line chemotherapy with FOLFIRI and bevacizumab. Primary endpoint will be overall survival, defined as the time elapsed from the date of randomization to the date of patient death due to any cause, or the last date the patient was known to be alive.
Secondary Objectives Progression free survival, Quality of life, Health resource utilisation and economic evaluation, Toxicity and incidence of adverse events
The study regimen includes:
Strategy A: FOLFOX-4 followed, after progression, by irinotecan/cetuximab Strategy B: irinotecan/cetuximab followed, after progression, by FOLFOX-4 Patients will be randomly assigned to one of the two treatment sequences (with 1:1 ratio) using a block design randomization procedure stratified according to center.
The patient accrual period is planned for approximately 36 months. To assess OS, all pts will be followed for up to 18 months after the last patient is randomised. The maximum estimated study duration is approximately 54 months.All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.
Detailed description
Target population:
Patients with histologically confirmed metastatic colorectal cancer progressed after a first line treatment containing FOLFIRI and BEV
Inclusion criteria:
- Age >18 < 75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- ECOG performance status 0-1 at study entry
Endpoints:
- Response Rate, Disease control rate, The duration of overall response, Overall survival, PFS, Time to treatment failure, Quality of Life, Incidence of AEs, Frequency and nature of serious adverse reactions (SADRs), Premature withdrawals
Statistical methods:
Assuming a randomization ratio of 1:1, 282 deaths are required in order to achieve a power of 80% of detecting a hazard ratio of 0.72 in favour of one of the two sequences, translating in an increase of median survival time from 10 to 14 months, with a type I error of 5%, two-sided, using the Mantel-Cox version of the log-rank test. With a uniform accrual period of 3 years and a follow-up of 18 months, about 350 patients will be needed to reach the target number of events.
All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.
All OS and PFS curves will be drawn with the Kaplan-Meier method. Results will be presented as Hazard Ratio (HRs) and their 95% Confidence Interval (CIs).
On annual basis, starting from the second year, an interim analysis will be conducted. In principle, no formal stopping rule will be applied, unless otherwise suggested by the DSMC. Safety reports will be drawn on annual basis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cetuximab/Irinotecan | Experimental | Drug: Irinotecan/CetuximabCetuximab/irinotecan followed, after progression, by FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil) |
| FOLFOX 4 | Active comparator | Drug: FOLFOX-4FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil) followed, after progression, by irinotecan/cetuximab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age >18 <75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- Performance Status (ECOG-PS) 0-1 at study entry
- Neutrophils ≥ 1.5 x 1039/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL
Key exclusion criteria (5 listed)
- History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
- Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
- History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake
- Known grade 3 or 4 allergic reaction to any of the components of the treatment
- Known drug abuse/ alcohol abuse
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 |
|---|---|---|
| FOLFOX-4Also: Oxaliplatin, 5FU, LeucovorinDay 1: OXA will be administered as a 85 mg/m2 iv infusion over 2 hours; Leucovorin as a 100 mg/m2 infusion over 2 hours, 5-FU will be given as a 400 mg/m2 bolus injection, and then as a 600 mg/m2 continuous infusion over 22 hours after the first infusion Day 2: Leucovorin 100 mg/m2 (alone), followed by 5-FU 400 mg/m2 bolus injection, and 5-FU 600 mg/m2 continuous infusion after the first infusion Cycle length is 2 weeks comprising approximately 48 hours of infusion and 12 days of rest. Cycles are to be repeated every second week for a total of either 6 (12 weeks) or 12 cycles (24 weeks). | Drug | FOLFOX 4 |
| Irinotecan/CetuximabAlso: CPT11/CetuximabCET 400 mg/m2 intravenously via infusion pump given over a 120 min time and weekly CET infusions at a maintenance dose of 250 mg/m2 given over a 60 min time. IRI 180 mg/m2 iv infusion over 30-90 min. Cycle length is 2 weeks and it is to be repeated until disease progression. | Drug | Cetuximab/Irinotecan |
Primary outcome
Overall Survival
Time frame: the time from the date of randomisation to the date of death
1 secondary outcome
Progression free survival
Time frame: the time relapsed from the date of randomization and the date of progression after third-line treatment or death
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 15 Jul 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
32 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 FOLFOX-4 and Irinotecan/Cetuximab in people with Metastatic Colorectal Cancer, run by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente at 32 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 11 inclusion and 5 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 15 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 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 Survival (time frame: the time from the date of randomisation to the date of death). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2015.