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

NCT04397601 | Unknown DMC FDA Drug

• 1 other identifier: 04/20
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS).

  OS will be measured from treatment start until death from any cause.

  3 years

Secondary Outcomes (3)

• Toxic effects.

  3 years

• Responses' duration.

  3 years

• Progression-free survival (PFS).

  3 years

Other Outcomes (2)

• Serum level of VEGF-A (Vascular Endothelial Growth Factor-A).

  3 years

• Serum level of PlGF (Placental Growth Factor).

  3 years

Study Arms (2)

A

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

Drug: Folfiri/Bevacizumab

B

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

Drug: Folfiri/Aflibercept

Interventions

Folfiri/Bevacizumab 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.

A

Folfiri/Aflibercept 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.

B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

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

Naples, 80131, Italy

RECRUITING

Related Publications (2)

• 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.

  PMID: 31456948 BACKGROUND

• 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.

  PMID: 33854566 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; aflibercept

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alessandro Ottaiano, MD

  SSD-Innovative Therapies for Abdominal Metastases

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandro Ottaiano, MD

CONTACT

0815903510; a.ottaiano@istitutotumori.na.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 21, 2020
• Study Start: May 11, 2020
• Primary Completion: May 11, 2023
• Study Completion: May 11, 2024
• Last Updated: May 21, 2020

Record last verified: 2020-05

Locations

IT (1)