Aflibercept or Bevacizumab as Second-line Treatment of RAS Mutated Metastatic Colorectal Cancer

NCT ID: NCT04397601

Last Updated: 2020-05-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 220 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-11
• Study Completion Date: 2024-05-11

Brief 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 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

A

mCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab.

Folfiri/Bevacizumab

Intervention Type: DRUG

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.

B

mCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab.

Folfiri/Aflibercept

Intervention Type: DRUG

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.

Interventions

Folfiri/Bevacizumab

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.

Intervention Type: DRUG

Folfiri/Aflibercept

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, Naples

OTHER

Sponsor Role: lead

Responsible Party

Alessandro Ottaiano

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alessandro Ottaiano, MD

Role: PRINCIPAL_INVESTIGATOR

SSD-Innovative Therapies for Abdominal Metastases

Locations

SSD-Terapie Innovative Metastasi Addominali, Dipartimento di Oncologia Addominale, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale".

Naples, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Alessandro Ottaiano, MD

Role: CONTACT

a.ottaiano@istitutotumori.na.it

0815903510

Facility Contacts

Guglielmo Nasti, MD

Role: primary

g.nasti@istitutotumori.na.it

0815903510

References

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.

Reference Type: BACKGROUND

PMID: 31456948 (View on PubMed)

Ottaiano 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.

Reference Type: DERIVED

PMID: 33854566 (View on PubMed)

Other Identifiers

04/20

Identifier Type: -

Identifier Source: org_study_id