Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Capecitabine

Immunomodulating Agents

Oxaliplatin

Antimetabolites

Nelmastobart intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered on Day 1 of each cycle.

Capecitabine is administered orally for two weeks followed by a one-week rest period

Nelmastobart and Capecitabine

Soohyeon LEE, M.D., Ph.D.

JIWON LEE, M.D.

This is an open-label clinical trial aimed at evaluating the safety and efficacy of the combination treatment of nelmastobart with capecitabine in patients diagnosed with metastatic or recurrent colorectal cancer.

Colorectal cancer is the third most commonly diagnosed cancer in men and the second most common cancer in women worldwide, with an estimated 1.9 million new cases and 935,000 deaths in 2020, according to the World Health Organization. Patients with metastatic colorectal cancer typically undergo first-line treatment consisting of fluorouracil-based chemotherapy (oxaliplatin and irinotecan) with or without vascular endothelial growth factor (VEGF)-based therapy (primarily bevacizumab), and epidermal growth factor receptor (EGFR)-targeted therapies (in patients with RAS wild-type tumors). Second-line treatment options may include alternative chemotherapy regimens. Third-line treatment options are often limited for patients with metastatic colorectal cancer, as they tend to exhibit poor objective response rates and short progression-free survival. However, despite their good performance status, patients often encounter limited options for third-line treatment, resulting in a daunting and frustrating situation.

This study will enroll patients aged ≥18 years who are resistant or intolerant to oxaliplatin and irinotecan-based chemotherapy. The study will evaluate the safety of the Nelmastobart and capecitabine combination therapy in Phase 1b. After identifying the Recommended Phase 2 Dose (RP2D), the study will assess the efficacy of the Nelmastobart and capecitabine combination therapy in Phase 2.

Combination of Nelmastobart and Capecitabine Therapy in Metastatic Colorectal Cancer

Combination of Nelmastobart and Capecitabine Therapy in Metastatic Colorectal Cancer With Resistance or Intolerance to Oxaliplatin and Irinotecan-based Chemotherapy - A Single Arm, Phase 1b/2, Multicenter Study

The MTD was defined as the highest dose at which no dose limiting toxicity (DLT) was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.

PFS events is defined as the interval from the first dose of investigational treatment to the earlier of the first documentation of objective progressive disease (PD) or death from any cause,whichever comes first.

ORR is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.

Progression free survival (PFS) will be calculated from the first dose of investigational treatment until date of progression or death without progression, using the Kaplan-Meier method accompanied by determination of the median and its 95% confidence interval.

Korea University Anam Hospital

Professor

Disease Attributes

Micronutrients

Hematinics

Vitamins

Leucovorin

Fluorouracil

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

5-Fluorouracil, Leucovorin

Kun-Huei Yeh, M.D., Ph.D.

To determine the maximum tolerated dose and dose limiting toxicity of 5-FU and leucovorin with novel 48-hour infusion schedule, and to collect toxicity profile at different dose level of 5-FU/LV 48-hour infusion.

Colorectal cancer is one of the major in Taiwan.It caused 3128 deaths in 1999, and represented the No.3 cancer killer in both male and female population of Taiwan.

Recently, evidence has accumulated that weekly, 24-hour infusion of high-dose 5-FU may improve the response rate and survival time compared with 5-FU bolus regiment. In a randomized multicenter trial of metastatic colorectal cancer, Kohne et al reported an overall response rate of 44%and a median survival time of 16 months using a weekly-times-six schedule of infusional 5-FU (2600mg/m2 24-hours infusion). In another randomized study for advanced colorectal cancer, de Gramont et al reported a significantly better outcome in patients treated by a similar schedule which combined "bolus plus infusional" 5-FU compared to "bolus" 5-FU. These results suggest that 24-or 48-hour infusion of high-dose 5-FU is more effective than the conventional bolus schedules.

A Phase I Trial of HDFL48 in Recurrent or Metastatic Colorectal Cancers

A Phase I Trial of HDFL48(Weekly 48-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin) in Recurrent or Metastatic Colorectal Cancers

National Taiwan University Hospital

Levoleucovorin

Aflibercept

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Day 1. Aflibercept + FOLFIRI

* aflibercept(Zaltrap): 4 mg/kg IV infusion for over 1hr (Do not administer as an IV push or bolus)
* Folinic acid: 400 mg/m2 IV infusion for over 2 hours
* Irinotecan: 150 mg/m2 IV infusion for over 1 hours
* 5-FU: 400 mg/m2 IV bolus injection for over 5 minute
* 5-FU: 2400 mg/m2 IV continuous infusion for 46 hours every 2 weeks until progression disease or death or unacceptable toxicity

Aflibercept + FOLFIRI

Joong Bae Ahn, MD, PhD

Based on the pervious data, aflibercept in combination with FOLFIRI is one of the effective 2nd line treatment option in advanced colorectal cancer. In this study, we prospectively assess the efficacy of 2nd line aflibercept in combination with FOLFIRI in advanced colorectal cancer in terms of progression-free survival. We further assess the efficacy according to the type of 1st line treatment. plasma biomarker study (HGF, VEGF-A, VEGF-D, IFN-γ, Angiopoietin-2, sICAM-1, sVCAM-1, TIMP-1, PIGF (HS), IL-6 (HS), IL-8 (HS), sNeuropilin-1, Thrombospondin-2 , Osteopontin , sVEGFR1, sVEGFR2, sVEGFR3) , overall survival (OS)OS, objective response rate (ORR), and safety are also assessed as the 2ndary objectives.

This is a prospective, multicenter, open-label, single arm study. Patients will be considered "on study" upon signing the written informed consent form (ICF). The study consists of a baseline period, followed by a treatment period, consisting of 14-day treatment cycles, which will end by a 30-day Follow-up visit, which in turn, will be followed by a post-treatment follow-up period.

Patients will be evaluated for PFS then be followed on study until death or until cut-off date for final analysis of OS has been reached, whichever comes first.

During the 21-day baseline period, all baseline procedures will have to be performed within defined timelines, including review of eligibility criteria During the treatment period, the study treatment, aflibercept combined with FOLFIRI will be administered every 2 weeks unless a definitive treatment discontinuation criterion is met. Cycle lengths may be extended in case of unresolved toxicity.

Imaging to document tumor response and progressive disease will take place every 6 weeks and will continue to be done during the follow-up period in case of early study treatment discontinuation (i.e. prior to documented progression). Once disease progression is documented, patients will be followed every 2 months for survival status and collection of data regarding further anticancer therapy, until death or until the study cutoff date, whichever comes first.

The patients will be followed for safety for a minimum of 30 days following the last administration of the study treatment (30-day Follow-up visit). Beyond this date, all study drug related AEs and all SAEs should be followed until resolution/stabilization. Study drug-related AEs brought to the attention of the investigator at any time after the 30-day Follow-up visit should be recorded in the case report form (CRF).

Plasma Biomarker for Aflibercept in Advanced Colorectal Cancer

Efficacy and Biomarker Exploration of 2nd Line Aflibercept in Combination With FOLFIRI in Advanced Colorectal Cancer

progressive disease (PD) or death, whichever occurs first. Results will be summarized by arm

* Kaplan-Meier method for survival function estimate
* Stratified Cox proportional hazard regression for hazard ratio (HR) estimate

Yonsei University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination of Nelmastobart and Capecitabine Therapy in Metastatic Colorectal Cancer	NCT05990543	Recurrent or Me...	Nelmastobart an...	18 Years -	Korea University Anam Hospital
A Phase I Trial of HDFL48 in Recurrent or Metastatic Colorectal Cancers	NCT00155558	Recurrent or Me...	5-Fluorouracil,...	18 Years -	National Taiwan University Hospital
A Phase I Trial of HDFL48 in Recurrent or Metastatic Colorectal Cancers	NCT00155558	Recurrent or Me...	5-Fluorouracil,...	18 Years -	National Taiwan University Hospital
Plasma Biomarker for Aflibercept in Advanced Colorectal Cancer	NCT04810585	Recurrent or Me...	Aflibercept + F...	19 Years -	Yonsei University
Combination of Nelmastobart and Capecitabine Therapy in Metastatic Colorectal Cancer	NCT05990543	Recurrent or Me...	Nelmastobart an...	18 Years -	Korea University Anam Hospital

Spots Global Cancer Trial Database for recurrent or metastatic colorectal cancer