Metastatic Colorectal CancerARBITRATIONNCT04397601
Aflibercept or Bevacizumab as Second-line Treatment of RAS Mutated Metastatic Colorectal Cancer
An observational study of Metastatic Colorectal Cancer, run by National Cancer Institute, Naples at 1 site in Italy.
Trial summary
Colorectal cancer is the third most frequent neoplasm after prostate and lung in man and breast and lung cancers in woman from Western Countries. The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Folfiri/Bevacizumab and Folfiri/Aflibercept
- Type of treatment
- Injection or infusion
- How many people
- 220 participants
- Where
- 1 siteItaly
- Study dates
- 11 May 2020to 11 May 2024
- Phase
- Observational
- 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
Study population: mCRC RAS mutated patients progressing at with first-line chemotherapy with at first-line chemotherapy based on fluoropyrimidines, oxaliplatin and bevacizumab.
Who may be able to join
- Cytological or histological diagnosis of RAS mutated mCRC;
- progression at first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab;
- stage IV;
- age <75 years;
- ECOG Performance Status 0 or 1;
- life expectancy> 3 months;
- negative pregnancy test for all potentially childbearing women.
Who cannot join
- presence of primary non-treated stenosing colorectal neoplasm;
- active or uncontrolled infections or bleedings;
- other concomitant uncontrolled diseases or blood laboratory values contraindicating the study drugs at clinician evaluation;
- presence of brain metastases;
- refusal or inability to provide informed consent;
- impossibility to guarantee follow-up.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
SSD-Terapie Innovative Metastasi Addominali, Dipartimento di Oncologia Addominale, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale".
Naples, 80131
Guglielmo Nasti, MD, 0815903510, g.nasti@istitutotumori.na.it
About this study
Official title: AflibeRcept or Bevacizumab In Combination With Folfiri as Second-line Treatment of RAS Mutated metastaTIc cOlorectal Cancer patieNts
Colorectal cancer is the third most frequent neoplasm after prostate and lung in man and breast and lung cancers in woman from Western Countries. The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients who benefit from specific therapies. In this context, the assessment of RAS (N- and K-) oncogene mutations is able to predict the response to anti-EGFR agents being mutated RAS mCRC patients resistant to these drugs. In this group of patients the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant. Still to date there are no studies to guide oncologists in the selection of the best anti-angiogenic drug (bevacizumab beyond progression vs aflibercept) after failure of the first-line chemotherapy in RAS-M mCRC patients. The present is the first observational, pragmatic, prospective study aimed to report outcomes of mCRC patients treated with folfiri plus bevacizumab versus folfiri plus aflibercept in second-line treatment of mRAS mCRC. Furthermore, the serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor-A and C (VEGF-A and C), stromal cell-derived factor-1 (SDF-1), platelet-derived growth factor beta (PDGF-β), basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) and Placental Growth Factor (PlGF), will be evaluated before starting second-line chemotherapy with bevacizumab or aflibercept in order to evidence any pattern related to response and/or prognosis. The hypothesis is that knowledge of eventual unbalance of these factors could help to select the best anti-angiogenic drug in second-line treatment of mRAS mCRC patients.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Folfiri/Bevacizumab, Folfiri/Aflibercept
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folfiri/BevacizumabDrug
Irinotecan (180 mg/m2), leucovorin (400 mg/m2), fluorouracil as an intravenous bolus of 400 mg/m2, and fluorouracil as a continuous 46-h infusion of 2400 mg/m2 in combination with bevacizumab (5 mg/kg) on day 1 of each 14-day cycle.
Folfiri/AfliberceptDrug
Irinotecan (180 mg/m2), leucovorin (400 mg/m2), fluorouracil as an intravenous bolus of 400 mg/m2, and fluorouracil as a continuous 46-h infusion of 2400 mg/m2 in combination with aflibercept (4 mg/kg) on day 1 of each 14-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| A | mCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab. Receives: Drug: Folfiri/Bevacizumab | |
| B | mCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab. Receives: Drug: Folfiri/Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS).
OS will be measured from treatment start until death from any cause.
Measured: 3 years
Secondary outcomes (3)
Toxic effects.
Toxic effects will be assessed by CTCAE of the National Cancer Institute, version 4.0, June 14, 2010.
Measured: 3 years
Responses' duration.
Time elapsed from date of response to progression occurrence.
Measured: 3 years
Progression-free survival (PFS).
PFS will be determined from the date of treatment start until progression.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2020
- Study start11 May 2020
- Primary completion11 May 2023 (estimated)
- Study completion11 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Naples
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessandro Ottaiano, National Cancer Institute, Naples
- Investigators
- Alessandro Ottaiano, MD, Principal investigator, SSD-Innovative Therapies for Abdominal Metastases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04397601
- Sponsor's protocol ID
- 04/20
- Acronym
- ARBITRATION
- Status last verified
- May 2020
- First submitted
- 13 May 2020
- Last updated
- 21 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Complete study protocol will be published.
Publications
Ottaiano A, Capozzi M, Tafuto S, De Stefano A, De Divitiis C, Romano C, Avallone A, Nasti G. Folfiri-Aflibercept vs. Folfiri-Bevacizumab as Second Line Treatment of RAS Mutated Metastatic Colorectal Cancer in Real Practice. Front Oncol. 2019 Aug 13;9:766. doi: 10.3389/fonc.2019.00766. eCollection 2019.
PubMed 31456948Ottaiano A, Scala S, Santorsola M, Trotta AM, D'Alterio C, Portella L, Clemente O, Nappi A, Zanaletti N, De Stefano A, Avallone A, Granata V, Notariello C, Luce A, Lombardi A, Picone C, Petrillo A, Perri F, Tatangelo F, Di Mauro A, Albino V, Izzo F, Rega D, Pace U, Di Marzo M, Chiodini P, De Feo G, Del Prete P, Botti G, Delrio P, Caraglia M, Nasti G. Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol. Ther Adv Med Oncol. 2021 Mar 24;13:1758835921989223. doi: 10.1177/1758835921989223. eCollection 2021.
PubMed 33854566
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AflibeRcept or Bevacizumab In Combination With Folfiri as Second-line Treatment of RAS Mutated metastaTIc cOlorectal Cancer patieNts
- ClinicalTrials.gov ID
- NCT04397601
- Acronym / sponsor ID
- ARBITRATION / 04/20
- Conditions
- Metastatic Colorectal Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Study start
- 11 May 2020 (actual)
- Primary completion
- 11 May 2023 (estimated)
- Study completion
- 11 May 2024 (estimated)
- First posted
- 21 May 2020 (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.
Colorectal cancer is the third most frequent neoplasm after prostate and lung in man and breast and lung cancers in woman from Western Countries. The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients who benefit from specific therapies. In this context, the assessment of RAS (N- and K-) oncogene mutations is able to predict the response to anti-EGFR agents being mutated RAS mCRC patients resistant to these drugs. In this group of patients the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant. Still to date there are no studies to guide oncologists in the selection of the best anti-angiogenic drug (bevacizumab beyond progression vs aflibercept) after failure of the first-line chemotherapy in RAS-M mCRC patients. The present is the first observational, pragmatic, prospective study aimed to report outcomes of mCRC patients treated with folfiri plus bevacizumab versus folfiri plus aflibercept in second-line treatment of mRAS mCRC. Furthermore, the serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor-A and C (VEGF-A and C), stromal cell-derived factor-1 (SDF-1), platelet-derived growth factor beta (PDGF-β), basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) and Placental Growth Factor (PlGF), will be evaluated before starting second-line chemotherapy with bevacizumab or aflibercept in order to evidence any pattern related to response and/or prognosis. The hypothesis is that knowledge of eventual unbalance of these factors could help to select the best anti-angiogenic drug in second-line treatment of mRAS mCRC patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | – | Drug: Folfiri/BevacizumabmCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab. |
| B | – | Drug: Folfiri/AfliberceptmCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- mCRC RAS mutated patients progressing at with first-line chemotherapy with at first-line chemotherapy based on fluoropyrimidines, oxaliplatin and bevacizumab.
Key inclusion criteria (7 listed)
- Cytological or histological diagnosis of RAS mutated mCRC;
- progression at first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab;
- stage IV;
- age <75 years;
- ECOG Performance Status 0 or 1;
Key exclusion criteria (6 listed)
- presence of primary non-treated stenosing colorectal neoplasm;
- active or uncontrolled infections or bleedings;
- other concomitant uncontrolled diseases or blood laboratory values contraindicating the study drugs at clinician evaluation;
- presence of brain metastases;
- refusal or inability to provide informed consent;
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 |
|---|---|---|
| Folfiri/BevacizumabIrinotecan (180 mg/m2), leucovorin (400 mg/m2), fluorouracil as an intravenous bolus of 400 mg/m2, and fluorouracil as a continuous 46-h infusion of 2400 mg/m2 in combination with bevacizumab (5 mg/kg) on day 1 of each 14-day cycle. | Drug | A |
| Folfiri/AfliberceptIrinotecan (180 mg/m2), leucovorin (400 mg/m2), fluorouracil as an intravenous bolus of 400 mg/m2, and fluorouracil as a continuous 46-h infusion of 2400 mg/m2 in combination with aflibercept (4 mg/kg) on day 1 of each 14-day cycle. | Drug | B |
Primary outcome
Overall Survival (OS).
Time frame: 3 years
OS will be measured from treatment start until death from any cause.
3 secondary outcomes
Toxic effects.
Time frame: 3 years
Responses' duration.
Time frame: 3 years
Progression-free survival (PFS).
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2020.
- Background: PubMed 31456948Ottaiano A, Capozzi M, Tafuto S, De Stefano A, De Divitiis C, Romano C, Avallone A, Nasti G. Folfiri-Aflibercept vs. Folfiri-Bevacizumab as Second Line Treatment of RAS Mutated Metastatic Colorectal Cancer in Real Practice. Front Oncol. 2019 Aug 13;9:766. doi: 10.3389/fonc.2019.00766. eCollection 2019.
- Derived from this study: PubMed 33854566Ottaiano A, Scala S, Santorsola M, Trotta AM, D'Alterio C, Portella L, Clemente O, Nappi A, Zanaletti N, De Stefano A, Avallone A, Granata V, Notariello C, Luce A, Lombardi A, Picone C, Petrillo A, Perri F, Tatangelo F, Di Mauro A, Albino V, Izzo F, Rega D, Pace U, Di Marzo M, Chiodini P, De Feo G, Del Prete P, Botti G, Delrio P, Caraglia M, Nasti G. Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol. Ther Adv Med Oncol. 2021 Mar 24;13:1758835921989223. doi: 10.1177/1758835921989223. eCollection 2021.
- Individual participant dataSharing planned: Undecided. Complete study protocol will be published.
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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.
Alessandro Ottaiano, MD principal investigator
SSD-Innovative Therapies for Abdominal Metastases
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Colorectal Cancer, run by National Cancer Institute, Naples 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?
The sponsor lists 7 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 21 May 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.
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?
Contact Alessandro Ottaiano, MD (0815903510, a.ottaiano@istitutotumori.na.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS). (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04397601, which also lists 2 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 21 May 2020.