Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Folinic Acid

SHORT-COURSE RT

FOLFOXIRI

* IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
* OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
* LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
* 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.

Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy

Lederfolin

5-Fluorouracil

Short-course radiotherapy

Roberto Moretto, MD

The aim of the ShorTrip trail is to evaluate the activity and the safety of total neoadjuvant strategy with FOLFOXIRI as consolidation therapy preceded by short-course radiotherapy and followed by surgery in LARC patients.

This is a prospective, open-label, multicentre, phase II single arm trial. Eligible patients with middle-high LARC will receive short-course radiotherapy followed by consolidation chemotherapy with FOLFOXIRI and surgery.

The primary objective of this trial is to evaluate the rate of complete pathologic response (pCR)

Short-course Radiotherapy Followed by Consolidation Chemotherapy. 2021-001206-29

Phase II Study of Short-course Radiotherapy Followed by Consolidation Chemotherapy With the Triplet FOLFOXIRI as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: the ShorTrip Study

Correlation of FFS and pCR with ctDNA status, assessed at prespecified timepoints during the study treatment

Pathological complete response rate, defined as the percentage of patients, relative to the total of enrolled subjects, with the absence of residual tumour cells in the resected specimens. pCR will be assessed by tumour regression grade according to Dworak et al, at the histopathological exam

Overall toxicity rate, defined as the percentage of patients, relative to the total of enrolled subjects, who receive radiotherapy and at least one cycle of chemotherapy, experiencing any adverse event, according the RTOGTC during SCRT, and according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the consolidation chemotherapy

G3/4 toxicity rate, is defined as the percentage of patients, relative to the total of enrolled subjects, who receive radiotherapy and at least one cycle of chemotherapy, experiencing a specific adverse event of grade 3/4, according the RTOGTC during SCRT, and according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the consolidation chemotherapy.

R0 Resection Rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing R0 resection of primary tumour. R0 surgery is defined as microscopically margin-negative resection at the histopatological exam

Failure-free survival (FFS) is defined as the time from enrollment to one of the following events: non-radical surgery (non R0/R1) of the primary tumour, intrapelvic recurrence after R0/1 resection of the primary tumour, distant relapse, second primary tumour or death from any cause, whichever occurred first. The determination of disease progression will be based on investigator-reported measurements. Patients who are alive without having one of the above events at the end of the study will be censored at their last radiological assessment

Overall Survival (OS) is defined as the time from enrolment to death from any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive

Time to distant metastases, is defined as the time from enrolment to the radiological evidence of distant metastases. The determination of the evidence of distant metastases will be based on investigator-reported measurements. Patients who are died or alive without having distant metastases at the end of the study will be censored at the date of death or their last radiological assessment, respectively

Time to locoregional failure is defined as the time from the enrolment to non-radical surgery of the primary tumour (non R0/R1 resection) or intrapelvic recurrence after R0/1 resection of the primary tumour. The determination of the intrapelvic recurrence will be based on investigator-reported assessment. Patients who are died or alive without having non-radical surgery or intrapelvic recurrence at the end of the study will be censored at the date of death or at their last radiological assessment

Clinical complete response (cCR) rate, defined as the percentage of patients, relative to the total of enrolled subjects, with the absence of residual tumour (cT0cN0) at the radiological and endoscopic staging after neoadjuvant treatment.

Major pathological response (MPR) rate, defined as the percentage of patients, relative to the total enrolled subjects, achieving TRG1-2 sec Mandard or TRG3-4 sec Dworak at the histopathological exam

Surgical mortality, defined as the percentage of patients, relative to the total of enrolled subjects, experiencing death within 30 days after the surgery

Surgical morbidities, defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any post-operative complications within 30 days after the surgery

Quality of Life, (QoL) assessed using the EORTC QLQ-C30, will be evaluate at specific time-points (baseline, after radiotherapy, and chemotherapy, after surgery and during follow-up) and will be assessed through descriptive summary statistics

Quality of Life, (QoL) assessed using the EORTC QLQ-CR29, will be evaluate at specific time-points (baseline, after radiotherapy, and chemotherapy, after surgery and during follow-up) and will be assessed through descriptive summary statistics

Quality of Life, (QoL) assessed using the EuroQol EQ-5D questionnaires, will be evaluate at specific time-points (baseline, after radiotherapy, and chemotherapy, after surgery and during follow-up) and will be assessed through descriptive summary statistics

Rectal Continence, assessed using LARS scores, will be evaluate at specific time-points (baseline, after radiotherapy, and chemotherapy, after surgery and during follow-up) and will be assessed through descriptive summary statistics

Rectal Continence, assessed using St. Mark Continence scores, will be evaluate at specific time-points (baseline, after radiotherapy, and chemotherapy, after surgery and during follow-up) and will be assessed through descriptive summary statistics

Gruppo Oncologico del Nord-Ovest

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Esophageal Neoplasms

Pancreatic Neoplasms

Stomach Neoplasms

Urinary Bladder Neoplasms

Liver Neoplasms

Biliary Tract Neoplasms

Gallbladder Neoplasms

Biliary Tract Diseases

Gallbladder Diseases

Esophageal Cancer

Pancreatic Cancer

Stomach Cancer

Biliary Tract Cancer

Gallbladder Cancer

Hematinics

Anti-Infective Agents

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Cisplatin

Epirubicin

Camptothecin

Liver Extracts

Taxane

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Patients operated for colorectal cancer with or without liver metastasis undergoing a chemotherapy treatment after surgery

Patients operated for esophagus/gastric cancer undergoing a chemotherapy treatment after surgery

Patients operated for biliary duct cancer undergoing a chemotherapy treatment after surgery

Patients operated for pancreatic cancer undergoing a chemotherapy treatment after surgery

The enrolled patients after the surgical operation will undergo to the adjuvant chemotherapy treatment

Nab paclitaxel

Luca Morelli, Prof

Vittoria Raffa, Prof

Enrico Vasile, Dr

Gregorio Di Franco, MD

Alice Usai, MSc

The study consists in a co-clinical trial by using zebrafish embryos. Specifically, an observational prospective clinical trial on patients operated of epato-biliar-pancreatic cancers and gastro-intestinal cancers undergoing a chemotherapy treatment will be run concurrently to an animal trial on zebrafish embryos xenotransplanted with patient cancer cells in order to demonstrate that zebrafish model is able to predict the therapeutic regimen with the best efficacy for each patient.

In the last years, a new concept of personalised medicine called 'Mouse Avatars' or 'co-clinical trials' has emerged. Development of mouse avatars implicates implantation of patient tumour samples in mice for use in drug efficacy studies. This model allows conducting preclinical trials in parallel with ongoing human phase I/II clinical trials. Murine and patient trials are conducted concurrently, and information obtained from the murine system is used for clinical management of the patient's tumour. The advantage of this approach is that each patient has his/her own tumour growing in an in vivo system, thereby allowing the identification of a personalised therapeutic approach. Such approach eliminates the cost and toxicity associated with non-targeted chemotherapy. Unfortunately, nowadays, it is clear that co-clinical trials using mouse avatars are not affordable because mice are expensive and time-consuming. The study challenge is to make Avatars available for every patient and the approach sustainable for the National Healthcare Systems. To implement this concept, the investigators propose to replace mouse Avatars with zebrafish Avatars. Indeed, the investigators propose to run co-clinical trials by using zebrafish embryos. Zebrafish embryos as model for human cancer cell xenografts offer several advantages:

1. Rejection-free model. In zebrafish thymus is not working until 9 days post-fertilization (dpf), allowing rejection-free xenografts during this period. Indeed, the use of expensive immune-permissive strains is not required, in sharp contrast to the mouse model.
2. Very low cost of husbanding.
3. Reduced amount of testing material. Zebrafish experiments require much less material to assess drug efficacy.
4. Short time for the analysis of xenotransplants. The time required for a drug efficacy study is 5 days, as opposite to several weeks or months in the mouse model.
5. Low experimental cost and simple procedures. The zebrafish produces large number of embryos with each fecundation (hundreds). This provides statistical power to the analysis and facilitates the collection of a large number of data.
6. Low ethical impact. Zebrafish is classified as insentient from fecundation to the time at which embryos become capable of independent feeding (120 hours post fertilization, hpf); therefore, during this time it does not require a license according to the Directive 2010/63/EU.
7. Data collected in zebrafish are relevant to humans. Zebrafish genome is closely related to that of humans. For instance, remarkable similarity in molecular signalling processes, cellular structure, anatomy, and physiology has been observed between zebrafish and other high-order vertebrates, including humans. This accounts for the exponential increase in the use of zebrafish in drug discovery during the last two decades.

Collectively, these points outline the remarkable advantages of the zebrafish Avatar over the mouse Avatar, paving the way for a realistic and cost-sustainable implementation of the co-clinical trials.

Specifically, the aim of the study is to perform an observational prospective clinical trial on patients operated of epato-biliar-pancreatic cancers and gastro-intestinal cancers undergoing a chemotherapy treatment in order to demonstrate that zebrafish Avatar is able to predict the therapeutic regimen with the best efficacy for each patient. To this effect, 120 patients meeting the trial inclusion criteria will be enrolled over a 18 months period. In this study, a fragment of tumor will be taken from the surgical specimen by the pathologist, fragmented and transplanted in the yolk of 48 hpf zebrafish embryos. The effect of different anticancer drugs and/or their combinations on the survival, proliferation and migration of the xenotransplanted cancer cells will be evaluated by exposing the xenotransplanted embryos to fish water modified with the drugs. The chemotherapy regimens to be tested in the xenografted embryos are selected in agreement to the common clinical practice, i.e.:

* fluoropyrimidines, platinum compounds, irinotecan, taxans (docetaxel) in stomach \& esophageal cancers
* fluoropyrimidines, platinum compounds, irinotecan, gemcitabine, nab paclitaxel in pancreatic/biliary cancers
* fluoropyrimidines, platinum compounds, irinotecan in colorectal cancers.

Embryos will be analysed 4, 24 and 48 hours post injection (hpi). Primary measures will include:

* cell proliferation
* cell migration
* formation of secondary masses
* induction of neo-angiogenesis

The enrolled patients after the surgical operation will undergo to the adjuvant chemotherapy treatment.

The comparative evaluation undertaken after closure of intake will be based on prospectively collected data on (i) clinical outcome and (ii) chemo-sensitivity data collected in zebrafish model.

Xenotransplantation of Primary Cancer Samples in Zebrafish Embryos

Comparative evaluation between prospectively collected data on clinical outcome and chemo-sensitivity data collected in zebrafish model

* Complete response (CR) - complete disappearance of clinical evidence of a tumour. Radiographically equivocal lesions must remain stable or regress.
* Partial response (PR) - 50% or greater decrease in the sum of products of the longest perpendicular diameters of measured lesion compared to baseline.
* Stable disease (SD) - no significant change in disease status. Lesion may show a \<50% decrease in sum of products of longest perpendicular diameters or an increase of \<25%.
* Progressive disease (PD) - a 25% increase in area of a lesion. Appearance of new lesions constitutes progressive disease.

The length of time from the start of treatment for the cancer that patients diagnosed with the disease are still alive

The length of time from the date of start of treatment for the disease until the disease starts to get worse or spread to other parts of the body

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Short-course Radiotherapy Followed by Consolidation Chemotherapy. 2021-001206-29	NCT05253846	Locally Advance...	Irinotecan Oxaliplatin Lederfolin 5-Fluorouracil Short-course ra... TME	18 Years - 70 Years	Gruppo Oncologico del Nord-Ovest
Short-course Radiotherapy Followed by Consolidation Chemotherapy. 2021-001206-29	NCT05253846	Locally Advance...	Irinotecan Oxaliplatin Lederfolin 5-Fluorouracil Short-course ra... TME	18 Years - 70 Years	Gruppo Oncologico del Nord-Ovest
Xenotransplantation of Primary Cancer Samples in Zebrafish Embryos	NCT03668418	Liver Cancer Pancreatic Canc... Gastric Cancer Esophageal Canc... Colo-rectal Can... Gall Bladder Ca... Biliary Tract C...	Fluorouracil Lederfolin Oxaliplatin Irinotecan Docetaxel Cisplatin Epirubicin Gemcitabine Nab paclitaxel	18 Years -	University of Pisa
Short-course Radiotherapy Followed by Consolidation Chemotherapy. 2021-001206-29	NCT05253846	Locally Advance...	Irinotecan Oxaliplatin Lederfolin 5-Fluorouracil Short-course ra... TME	18 Years - 70 Years	Gruppo Oncologico del Nord-Ovest

Spots Global Cancer Trial Database for lederfolin

Every month we try and update this database with for lederfolin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lederfolin

Every month we try and update this database with for lederfolin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lederfolin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.