Genotype-Guided Irinotecan for Colorectal and Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
Overseen byReema A Patel, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Reema A. Patel
Must not be taking: Irinotecan
Disqualifiers: Pregnancy, Uncontrolled illness, others
No Placebo Group
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a prospective, randomized study designed to compare genotype-guided dosing to usual care in patients with pancreas cancer and colorectal cancer who are UGT1A1 intermediate metabolizers (\*1/\*28) (heterozygotes) and usual UGT metabolizers (\*1/\*1). All patients will be assessed for UGT1A1 genotype at screening and those with intermediate or usual UGT1A1 genotypes (\*1/\*28, \*1/\*1) will be randomized to genotype-guided dosing versus usual care.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Irinotecan for colorectal and pancreatic cancer?
Research shows that Irinotecan, when used with other drugs like 5-fluorouracil, improves survival rates in patients with metastatic colorectal cancer. It has been effective as a second-line treatment, meaning it's used when initial treatments don't work, and studies suggest it could be beneficial in combination therapies.
12345Is irinotecan generally safe for humans?
Irinotecan, also known as CPT-11, can cause severe side effects, especially in people with certain genetic traits. Studies show that it can lead to serious blood-related toxicities and other severe reactions, particularly in patients with specific gene variations.
16789What makes the drug Irinotecan unique for treating colorectal and pancreatic cancer?
Irinotecan is unique because it is used in a genotype-guided approach, meaning treatment is tailored based on a patient's genetic makeup, which can help predict and manage potential side effects like hematologic toxicity (blood-related side effects). This personalized approach aims to improve treatment effectiveness and reduce adverse effects compared to standard treatments.
123510Eligibility Criteria
This trial is for adults over 18 with stage I-IV pancreatic or stage III-IV colorectal cancer who are about to start treatment. They must have a certain UGT1A1 gene type, good organ function, and an ECOG performance status of ≤1. Pregnant women, those not planned for treatment, previous irinotecan users, or patients with uncontrolled illnesses that could affect therapy adherence cannot join.Inclusion Criteria
I am fully active and can carry on all pre-disease activities without restriction.
I have had surgery or radiation, but no treatments with irinotecan.
My cancer can be measured by tests or scans.
+3 more
Exclusion Criteria
I do not have any severe illnesses that my doctor thinks could interfere with the treatment.
Pregnant women are excluded from this study
I am not scheduled for any cancer treatment.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive genotype-guided dosing or usual care for pancreas and colorectal cancer
6 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Participant Groups
The GENOCARE trial is testing whether adjusting the dose of Irinotecan based on the patient's specific genotype (UGT1A1) leads to better outcomes than usual care in treating pancreatic and colorectal cancers. Participants will be randomly assigned to either receive genotype-guided dosing or standard treatment.
2Treatment groups
Experimental Treatment
Active Control
Group I: Genocare GuidedExperimental Treatment1 Intervention
Group II: Usual CareActive Control1 Intervention
Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:
🇺🇸 Approved in United States as Camptosar for:
- Colorectal cancer
🇪🇺 Approved in European Union as Irinotecan for:
- Colorectal cancer
🇯🇵 Approved in Japan as Topotecin for:
- Colorectal cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Irinotecan for:
- Colorectal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of KentuckyLexington, KY
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Who Is Running the Clinical Trial?
Reema A. PatelLead Sponsor
References
UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. [2018]Irinotecan (CPT-11) is approved in metastatic colorectal cancer treatment and can cause severe toxicity. The main purpose of our study was to assess the role of different polymorphisms on the occurrence of hematologic toxicities and disease-free survival in high-risk stage III colon cancer patients receiving 5-fluorouracil (5FU) and CPT-11 adjuvant chemotherapy regimen in a prospective randomized trial.
Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer. [2018]Two randomized phase III trials with irinotecan as second-line treatment of metastatic colorectal cancer have shown that irinotecan (CPT-11, Camptosar) significantly improves survival when compared with best supportive care or continuous infusion of fluorouracil (5-FU) after failure of 5-FU. The combination of irinotecan and 5-FU/leucovorin produced a significantly higher response rate (40.8% vs 23.1%, P
The role of irinotecan in colorectal cancer. [2019]Irinotecan, also known as CPT-11, is a topoisomerase I inhibitor currently approved for use as a second-line agent in the treatment of advanced colorectal cancer. Preliminary reports from randomized studies exploring combinations of CPT-11 plus 5-fluorouracil have shown improved antitumor activity versus 5-fluorouracil-based treatments alone, and suggest a first-line role for these combination regimens. The role of CPT-11/5-fluorouracil regimens in the adjuvant setting is now being actively explored. Studies of single-agent CPT-11 in the first-line treatment of metastatic colorectal cancer have shown activity; however response rates do not appear to be superior to those seen with standard first-line 5-fluorouracil-based regimens. The use of specific molecular markers as prognostic indicators of response or resistance to specific chemotherapies may, however, permit the identification of a selected population of patients with tumor characteristics that would specifically favor consideration of up-front use of single-agent CPT-11.
A phase II study of irinotecan alternated with a weekly schedule of high-dose leucovorin and 48-hour 5-fluorouracil infusion in patients with metastatic colorectal cancer. [2018]To evaluate the activity and safety of an alternating schedule of irinotecan (CPT-11) with high-dose 5-fluorouracil (5-FU) given as a weekly 48-hour infusion in combination with leucovorin (LV) in the first-line treatment of metastatic colorectal cancer (MCRC) patients.
Irinotecan in the first-line treatment of colorectal cancer. [2018]Irinotecan (CPT-11 [Camptosar]) is currently approved for use as a second-line agent in the treatment of metastatic colorectal cancer. Phase II studies have also shown substantial single-agent activity of irinotecan in the first-line treatment of metastatic colorectal cancer. Response rates appear to be similar to those seen with standard first-line regimens, although direct randomized comparisons have not yet been reported. In the absence of definitive data showing irinotecan to be superior, its routine use as a single agent in the first-line treatment of colorectal cancer may be hard to justify, given the significant cost differential between irinotecan and current standard first-line regimens. Studies exploring combinations of irinotecan with fluorouracil may identify a first-line role for these combination regimens. Also, use of specific molecular markers may permit the identification of selected patients with tumor characteristics that would specifically favor consideration of upfront irinotecan monotherapy.
Clinical activity and benefit of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma pre-treated with fluorouracil-based chemotherapy. [2018]The purpose of this prospective study was to assess the efficacy, clinical benefit and safety of irinotecan (CPT-11) in patients with 5-fluorouracil-resistant metastatic colorectal cancer (CRC). Sixteen patients with World Health Organization (WHO) performance status
A phase I study of combination therapy with S-1 and irinotecan in patients with previously untreated metastatic or recurrent colorectal cancer. [2018]To investigate the combination of S-1 and irinotecan (CPT-11) as an alternative to infusional 5-fluorouracil/leucovorin plus CPT-11, we performed a phase I trial to determine the maximum tolerated dose, recommended dose (RD), and dose-limiting toxicities (DLTs) in patients with metastatic or recurrent colorectal cancer.
Clinical pharmacokinetics of irinotecan-based chemotherapy in colorectal cancer patients. [2019]Irinotecan (CPT-11) significantly improves the efficacy of colorectal cancer treatment, demonstrating a superior efficacy with respect to leucovorin-modulated 5-fluorouracil (5-FU), also in fluoropyrimidine-resistant neoplasms. Preclinical studies demonstrated the inhibition of topoisomerase I by CPT-11 active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), and the possible synergistic interaction with other drugs effective against colorectal cancer, including 5-FU and oxaliplatin. Because of the occurrence of toxicities due to the large interpatient variability in drug metabolism, irinotecan is a candidate for therapeutic drug monitoring and pharmacokinetic optimisation. New schedules of drug administration (i.e. prolonged infusion) have led to improved cytotoxic effect of irinotecan, which resulted in improved overall survival and time to relapse together with reduced toxicity in comparison with 5-FU-based regimens. Furthermore, the analysis of the conversion of irinotecan into SN-38 by carboxylesterase, the detoxification of irinotecan and SN-38 by CYP3A4 and UDP-glucuronosyl transferases, and the activity of excretory systems (i.e., cMOAT, P-gp and MRP) seems able to predict the interindividual variability in pharmacokinetics and pharmacodynamics, being possible to predict untolerable toxicities. Finally, pharmacogenetics may elucidate drug interaction and gene expression modulation by irinotecan, while pharmacokinetic/pharmacodynamic models represent a valuable approach to further define the pharmacologic profile ofirinotecan and improve its therapeutic index.
ABCB1, SLCO1B1 and UGT1A1 gene polymorphisms are associated with toxicity in metastatic colorectal cancer patients treated with first-line irinotecan. [2019]We tested specific gene polymorphisms known to be involved in the irinotecan (CPT-11) metabolic pathway. The combination of at least one SLCO1B1 521 T allele, one ABCB1 1236 C allele and one UGT1A1*28 variant 7 repeat demonstrated a statistically significant association with Grade 3/4 toxicities in metastatic colorectal cancer patients.
In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. [2019]Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells.