Abstract 2012
Background
5-fluorouracil (5-FU) in combination with the folate Leucovorin (LV) has been the cornerstone in the treatment of colorectal cancer (CRC) for decades. All folates currently approved for use in the clinical setting need to be metabolically activated to [6R] 5,10-methylenetetrahydrofolic acid ([6R]-MTHF), which is the active thymidylate synthase co-substrate that potentiates the effect of 5-FU. Arfolitixorin does not need multi step metabolic activation like currently available folates. It is therefore hypothesized that the administration of arfolitixorin will result in higher, and less individual variability, intracellular concentrations of the active thymidylate synthase co-substrate [6R]-MTHF in all patients compared to LV administration.
Trial design
Primary endpoint ORR by Blinded Independent Central Review (BICR) Key secondary endpoints Progression Free Survival (PFS) Duration of Response (DoR) Secondary endpoints Overall Survival (OS) Quality of Life (QoL) Safety and Tolerability Patients undergoing curative metastasis resection Study Design This is a randomized, multicenter, parallel-group, Phase III study to compare the efficacy of arfolitixorin versus LV in patients with mCRC treated with 5-FU, oxaliplatin, and bevacizumab. Patients will be randomized in a 1:1 ratio to either the investigational arm or the comparator arm. The study target is to randomize 440 patients in 18 months. An adaptive study design includes the possibility to increase the sample size to 660 patients as determined by the DSMB during the interim analysis to be conducted after 330 patients have conducted their 16 weeks scan. Key inclusion criteria: Adults > 18 years of age Colorectal adenocarcinoma verified by biopsy Non-resectable mCRC No prior treatment for first line mCRC ECOG performance status 0 or 1 Key exclusion criteria: Malignant tumors other than colorectal adenocarcinomas Less than 6 months since last anti-cancer treatment DPD deficiency Clinically significant cardiovascular disease Central nervous system metastases Study Countries Australia, Austria, Canada, France, Germany, Greece, Spain, Sweden and USA FPI: December 18, 2018.
Clinical trial identification
NCT03750786; 2017-004154-41.
Editorial acknowledgement
Legal entity responsible for the study
Isofol Medical AB.
Funding
Isofol Medical AB.
Disclosure
J. Tabernero: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Chugai; Advisory / Consultancy: Genetech Inc; Advisory / Consultancy: Genemab A/S; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Imugene Limited; Advisory / Consultancy: Inflection Biosciences Limited; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Kura Oncology; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Menarini; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Merus; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: Novartis. G. Prager: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Lilly; Advisory / Consultancy: Servier; Advisory / Consultancy: Taiho; Advisory / Consultancy: Bayer; Advisory / Consultancy: Halozyme; Advisory / Consultancy: BMS; Advisory / Consultancy: Cellgene; Advisory / Consultancy: Shire. S. Stintzing: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda; Advisory / Consultancy: Servier. H.J. Lenz: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Boehringer Ingelheim. H.P. Nygren: Shareholder / Stockholder / Stock options: Oncopeptides; Research grant / Funding (institution), Licensing / Royalties: Respos Pharma. C. Papadimitriou: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Genesis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck.
Resources from the same session
5458 - Baseline characteristics from CLARINET FORTE: Evaluating lanreotide autogel (LAN) 120 mg every 14 days in patients with progressive pancreatic or midgut neuroendocrine tumours during a standard first-line LAN regimen.
Presenter: Philippe Ruszniewski
Session: Poster Display session 2
Resources:
Abstract
1234 - Analysis of PD-1/PD-L1 blockade biomarker and immune infiltrates in Gastroenteropancreatic neuroendocrine carcinoma
Presenter: Jia Zhang Xing
Session: Poster Display session 2
Resources:
Abstract
1517 - Diabetes Is Associated With Pancreatic Neuroendocrine Tumors Growth and Metastasis
Presenter: Zhiyao Fan
Session: Poster Display session 2
Resources:
Abstract
2145 - Investigation of the reclassification of G1/G2 pancreatic neuroendocrine neoplasms by WHO 2017 classification
Presenter: Takahiro Yokose
Session: Poster Display session 2
Resources:
Abstract
3134 - Treatment with somatostatin analogues after radiopeptide therapy
Presenter: Daria Handkiewicz Junak
Session: Poster Display session 2
Resources:
Abstract
2191 - Safety and Tolerability of Surufatinib in Western Patients with Solid Tumors
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3253 - The impact of tumour absorbed dosimetry with survival outcomes after peptide receptor radionuclide therapy in metastatic neuroendocrine tumours.
Presenter: Rahul Ladwa
Session: Poster Display session 2
Resources:
Abstract
3581 - Opportunist and Serious Infections in Patients with Neuroendocrine Tumors Treated With Everolimus: A Multicenter Study of Real World Patients
Presenter: Carine Mauro
Session: Poster Display session 2
Resources:
Abstract
5374 - Establishment of Prognostic Nomogram Based on the Metastatic Lymph Nodes Ratio for Patients with Gastric Neuroendocrine Tumour
Presenter: yaobin lin
Session: Poster Display session 2
Resources:
Abstract
3951 - Neutrophil-lymphocyte ratio as an independent predictive factor in Neuroendocrine Neoplasms
Presenter: Sofia Ferreira
Session: Poster Display session 2
Resources:
Abstract