NCT02256800

Escalated Dose of Irinotecan in mCRC

Completed NA Last updated 17 November 2021

What this trial tests

NA trial testing UGT1A1 genotyping (6,6) in Metastatic Colorectal Cancer in 213 participants. Completed in 30 November 2017.

Timeline

13 August 2014

Primary endpoint
30 November 2017

30 November 2017

Quick facts

Lead sponsor	Jaw-Yuan Wang, MD, PhD
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	213
Start date	13 August 2014
Primary completion	30 November 2017
Estimated completion	30 November 2017
Sites	1 location across Taiwan

Drugs / interventions tested

• UGT1A1 genotyping (6,6)
• UGTIA1 genotyping (6,7)
• UGTIA1 genotyping (7,7)
• UGT1A1 non-genotyping
• bevacizumab (Avastin)
• irinotecan (irinotecan) — full drug profile →
• Leucovorin (leucovorin) — full drug profile →
• 5-FU (5-fu) — full drug profile →

Conditions studied

• Metastatic Colorectal Cancer — all drugs for Metastatic Colorectal Cancer →

Sponsor

Jaw-Yuan Wang, MD, PhD

Who can join

Adults 20 to 80, any sex, with Metastatic Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Metastatic diseases were found in 20-25% of patients with initial diagnosis of colorectal cancer and developed in up to 50% of patients. Owing to limited post-treatment response of 5-fluorouracil (5-FU) combined with leucovorin (LV) obtained in mCRC (metastatic colorectal cancer) patients, other therapeutic agents with different mechanisms were considered, such as irinotecan, a potent inhibitor of topoisomerase I, which is involved in the unwinding of DNA during replication. Bevacizumab is a humanized monoclonal antibody that inhibits tumor angiogenesis by blocking vascular endothelial growth factor (VEGF) and was the first antiangiogenic agent approved for the treatment of cancer.

Infusional fluorouracil/leucovorin plus irinotecan-based regimen (FOLFIRI) with bevacizumab has been widely used as first-line treatment for patients with metastatic colorectal cancer (mCRC). Recently, the investigators have shown that prospective analysis of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotyping for irinotecan dose escalation (FOLFIRI regimen) with combination of bevacizumab biweekly as the first-line setting in mCRC patients (ASCO Abstract #491 - 2013 Gastrointestinal Cancers Symposium).

In this study, the investigators will enroll approximately 320 mCRC patients (It was considered that an increase of response rate of 15% compared to conventional irinotecan dose of 180 mg/m2, and these were chosen as parameters with which to calculate the study power. Initial power calculation was suggested that a minimum of 140 patients in each group would be required to achieve statistical significance with a power of 80% at the 5% significance level. It is estimated that about 10% of 320 mCRC patients fail to complete the study). For these enrolled patients, the investigators will randomize and divide these patients into two groups: control group and study group. Control group includes mCRC patients who will receive the conventional regimen of FOLFIRI plus bevacizumab. Otherwise, patients in the study group will have genotyping of UGT1A1 before therapy, and dose escalating of irinotecan will depend on results of genotyping.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities.
   Tesfaye AA, Kamgar M, Azmi A, Philip PA. · · 2018 · cited 33× · PMID 29254387 · DOI 10.1080/14737140.2018.1417844
2. Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST).
   Tsai HL, Huang CW, Lin YW, Wang JH, et al · · 2020 · cited 29× · PMID 32829105 · DOI 10.1016/j.ejca.2020.05.031
3. Prospective analysis of UGT1A1 promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab plus FOLFIRI as the first-line setting: study protocol for a randomized controlled trial.
   Yeh YS, Tsai HL, Huang CW, Wang JH, et al · · 2016 · cited 17× · PMID 26811156 · DOI 10.1186/s13063-016-1153-3
4. A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.
   Lingaratnam S, Shah M, Nicolazzo J, Michael M, et al · · 2024 · cited 4× · PMID 38700261 · DOI 10.1111/cts.13781