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
5472 - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Presenter: Camilla Qvortrup
Session: Poster Display session 2
Resources:
Abstract
2037 - Updated survival analysis of the randomized phase III trial comparing S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (SALTO) by the Dutch Colorectal Cancer Group.
Presenter: Johannes Kwakman
Session: Poster Display session 2
Resources:
Abstract
3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.
Presenter: Keisuke Kazama
Session: Poster Display session 2
Resources:
Abstract
3183 - Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase 2 study
Presenter: Akitaka Makiyama
Session: Poster Display session 2
Resources:
Abstract
3233 - Biweekly TAS-102 and Bevacizumab as a Third-Line Chemotherapy for metastatic colorectal cancer: A Phase II Multicenter Clinical Trial (TAS-CC4 study)
Presenter: Yoichiro Yoshida
Session: Poster Display session 2
Resources:
Abstract
5907 - Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer
Presenter: Pashtoon Kasi
Session: Poster Display session 2
Resources:
Abstract
1866 - Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer
Presenter: Emilie Moati
Session: Poster Display session 2
Resources:
Abstract
2312 - High Circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab
Presenter: Jakob Schou
Session: Poster Display session 2
Resources:
Abstract
5602 - Clinical relevance of circulating tumor (ct)DNA genotyping for first line cetuximab-based treatment monitoring in metastatic colorectal cancer (mCRC): a prospective multicentric study
Presenter: JOANA Vidal Barrull
Session: Poster Display session 2
Resources:
Abstract
3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Presenter: Beili Wang
Session: Poster Display session 2
Resources:
Abstract