Aflibercept or Bevacizumab as Second-line Treatment of RAS Mutated Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Drug: Folfiri/BevacizumabDrug: Folfiri/Aflibercept
- Registration Number
- NCT04397601
- Lead Sponsor
- National Cancer Institute, Naples
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 220
- 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.
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description A Folfiri/Bevacizumab mCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab. B Folfiri/Aflibercept mCRC RAS mutated patients progressing to first-line chemotherapy with fluoropyrimidines, oxaliplatin and bevacizumab.
- Primary Outcome Measures
Name Time Method Overall Survival (OS). 3 years OS will be measured from treatment start until death from any cause.
- Secondary Outcome Measures
Name Time Method Toxic effects. 3 years Toxic effects will be assessed by CTCAE of the National Cancer Institute, version 4.0, June 14, 2010.
Responses' duration. 3 years Time elapsed from date of response to progression occurrence.
Progression-free survival (PFS). 3 years PFS will be determined from the date of treatment start until progression.
Trial Locations
- Locations (1)
SSD-Terapie Innovative Metastasi Addominali, Dipartimento di Oncologia Addominale, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale".
🇮🇹Naples, Italy