Genotype-driven Weekly Irinotecan Liposomes in Combination With Capecitabine-based Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

March 3, 2024 updated by: Ji Zhu, Zhejiang Cancer Hospital

Genotype-driven Phase I Study of Weekly Irinotecan Liposomes in Combination With Capecitabine-based Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

This study is a multicenter, open, and phase I dose increasing clinical study. Based on the UGT1A1 * 28 and * 6 genotypes of patients with locally advanced rectal cancer, determine the dose limiting toxicity (DLT) and maximum tolerable dose (MTD) of weekly irinotecan liposomes in concurrent chemoradiotherapy with capecitabine, investigate the tolerance of irinotecan liposome combined with capecitabine in concurrent chemoradiotherapy with locally advanced rectal cancer, and recommend the dosage for Phase II clinical study，and explore the pharmacokinetic characteristics of irinotecan liposomes combined with capecitabine.At the same time，Preliminary observe the efficacy and safety of irinotecan liposomes combined with capecitabine in chemoradiotherapy.The study plans to recruit 30 patients with advanced rectal cancer who have not received any therapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhejiang Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosed as rectal adenocarcinoma by histopathology, immunohistochemical pMMR or MSI-L, MSS;
  2. The baseline clinical stage is T2-4 and/or N+, which is not suitable for initial local resection to achieve curative effect;
  3. The distance between the tumor and the anus is<=10cm;
  4. No distant metastasis;
  5. Age range from 18 to 70 years old, regardless of gender;
  6. ECOG PS score 0-1 points;
  7. The UGT1A1 * 6 and UGT1A1 * 28 gene phenotypes are all wild-type (GG+6/6), unit point mutant (GG+6/7 or GA+6/6), and dual site mutant (GG+7/7 or AA+6/6 or GA+6/7);
  8. Not receiving chemotherapy or any other anti-tumor treatment before enrollment;
  9. Able to comply with the protocol during the research period;
  10. Sign written informed consent.

Exclusion Criteria:

  1. Diagnosed as rectal adenocarcinoma by pathological histology, and immunohistochemical dMMR or MSI-H;
  2. UGT1A1 * 6, UGT1A1 * 28 gene phenotype three site mutations (AA+7/7 or AA+6/7 or GA+7/7);
  3. Pregnant or lactating women
  4. Individuals with a history of other malignant diseases in the past 5 years, excluding cured skin cancer and cervical cancer in situ
  5. Individuals with a history of uncontrolled epilepsy, central nervous system disease, or mental disorders, whose clinical severity may be assessed by the researcher as hindering the signing of informed consent forms or affecting the patient's adherence to oral medication
  6. Clinically severe (i.e. active) heart disease, such as symptomatic coronary heart disease, NYHA grade II or more severe congestive heart failure, or severe arrhythmia requiring medication intervention (see Appendix 12), or a history of myocardial infarction within the past 12 months
  7. Organ transplantation requires immunosuppressive therapy
  8. Severe uncontrolled recurrent infections or other serious uncontrolled comorbidities
  9. The baseline blood routine and biochemical indicators of the subjects do not meet the following criteria: hemoglobin ≥ 90g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; ALT and AST ≤ 2.5 times the normal upper limit value; ALP ≤ 2.5 times the normal upper limit value; Serum total bilirubin<1.5 times the upper normal limit value; Serum creatinine<1 times the upper normal limit value; Serum albumin ≥ 30g/L
  10. Known individuals with dihydropyrimidine dehydrogenase (DPD) deficiency
  11. Individuals who are allergic to any research medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: irinotecan liposomes+capecitabine+chemoradiotherapy
There are three dose groups inciuding wild-type (GG+6/6)，unit site mutant (GG+6/7 or GA+6/6) and double sites mutant (GG+7/7 or AA+6/6 or GA+6/7)。Every group will receive irinotecan liposomes injection and capecitabine based chemoradiotherapy.
Drug: irinotecan liposomes+capecitabine
Radiotherapy：IMRT DT 50Gy/25Fx. Capecitabine: 625mg/m2 bid po d1-5 qw. For patients are double sites mutant (GG+7/7 or AA+6/6 or GA+6/7)，the intial dose of Irinotecan liposomes is 25mg/m2 weekly，for four weeks。 This study stratify cases by the "3+3" rule according to UGT1A1 * 6 and UGT1A1 * 28 phenotypes. Three cases were enrolled in each dose group, and if there was no DLT, they were promoted to the next dose group（an increase of 5mg/m2）; If there is 1 case of DLT, 3 cases will be reenrolled in the same dose group. If there is no new occurrence of DLT, it will be promoted to the next dose group. Otherwise, the study will be terminated; If there are 2 cases of DLT, the study will be terminated, and the previous dose group will be the maximum tolerated dose (MTD).
Other Names:
  • chemoradiotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
DLT（dose-limiting toxicity）
Time Frame: up to 6 months
Any adverse event that occurs during a research period and is related to Irinotecan liposomes the and meets a certain level or higher of CTCAE.
up to 6 months
MTD（maximum tolerable dose）
Time Frame: up to 6 months
the highest dose of exposure to a substance without causing serious toxic reactions.
up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhejiang Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 3, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 3, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 8, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CARTOnG-2401

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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