Clinical trial NCT04397601: Aflibercept or Bevacizumab as Second-line Treatment of RAS Mutated Metastatic Colorectal Cancer
Official title: AflibeRcept or Bevacizumab In Combination With Folfiri as Second-line Treatment of RAS Mutated metastaTIc cOlorectal Cancer patieNts
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Metastatic Colorectal Cancer
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2020-05-21
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: mCRC RAS mutated patients progressing at with first-line chemotherapy with at first-line chemotherapy based on fluoropyrimidines, oxaliplatin and bevacizumab.

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.


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.

Primary outcomes:
measure: Overall Survival (OS).
timeFrame: 3 years
Secondary outcomes:
measure: Toxic effects.
timeFrame: 3 years
measure: Responses' duration.
timeFrame: 3 years
measure: Progression-free survival (PFS).
timeFrame: 3 years
Other outcomes:
measure: Serum level of VEGF-A (Vascular Endothelial Growth Factor-A).
timeFrame: 3 years
measure: Serum level of PlGF (Placental Growth Factor).
timeFrame: 3 years
Locations:
city: Naples
country: Italy
facility: SSD-Terapie Innovative Metastasi Addominali, Dipartimento di Oncologia Addominale, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale".
Study officials:
affiliation: SSD-Innovative Therapies for Abdominal Metastases
name: Alessandro Ottaiano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.