NCT04227886

Brief Summary

Backgrounds: A multicenter randomized phase III trial (NCT02605265) proved that adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable. Purposes: This study aims to identify the predictive biomarkers (from patients' tumor biopsy samples and peripheral blood samples before neoadjuvant therapy) for predicting the response and toxicities to neoadjuvant therapy to stratify patients and optimize treatment strategy.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Dec 2019

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2019

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

December 30, 2019

Completed
15 days until next milestone

First Posted

Study publicly available on registry

January 14, 2020

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2021

Completed
Last Updated

January 14, 2020

Status Verified

January 1, 2020

Enrollment Period

1.1 years

First QC Date

December 30, 2019

Last Update Submit

January 11, 2020

Conditions

Rectal Neoplasm Malignant CarcinomaChemoradiotherapyNeoadjuvant TherapyPredictive BiomarkersAdenocarcinoma

Keywords

Neoadjuvant ChemoradiationPrediction ModelTreatment ResponseToxicitiesIrinotecanTissue RNAPlasma exosome

Outcome Measures

Primary Outcomes (2)

  • TRG

    Tumor regression grade

    Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy

  • Toxicities

    Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0

    Up to 2 years

Secondary Outcomes (4)

  • Overall Survival

    3 years

  • Progression-free Survival

    3 years

  • Local Control rate

    3 years

  • pCR

    Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy

Study Arms (4)

Good response

TRG of 0-1 is defined as good response.

Radiation: RadiationDrug: Capecitabine-Irinotecan Combination

Poor response

TRG of 2-3 is defined as poor response.

Radiation: RadiationDrug: Capecitabine-Irinotecan Combination

Light toxicity

No grade 3-4 toxicities occur during neoadjuvant therapy.

Radiation: RadiationDrug: Capecitabine-Irinotecan Combination

Heavy toxicity

Grade 3-4 toxicities occur during neoadjuvant therapy.

Radiation: RadiationDrug: Capecitabine-Irinotecan Combination

Interventions

RadiationRADIATION

Neoadjuvant radiotherapy consisted of 50 Gy in 25 fractions using intensity-modulated radiotherapy to the primary tumor and to mesorectal, presacral, and internal iliac lymph nodes.

Good responseHeavy toxicityLight toxicityPoor response
Capecitabine-Irinotecan CombinationDRUG

The concurrent chemotherapy consists of capecitabine 625 mg/m2 twice daily 5 days per week and combined with weekly irinotecan. The irinotecan dose was used based on UGT1A1 genotype of 80mg/m2 for UGT1A1\*1\*1 or 65mg/m2 for UGT1A1\*1\*28 weekly, followed by a cycle of XELIRI.

Good responseHeavy toxicityLight toxicityPoor response

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Stage T3 or T4 and/or N+ rectal adenocarcinoma cancer eligible for neoadjuvant chemoradiation

You may qualify if:

  • Pathological confirmed adenocarcinoma
  • Clinical stage T3-4 andor N+
  • The distance from anal verge less than 12 cm
  • No suspicious metastatic disease (M1)
  • ECOG PS 0-1
  • UGT1A1\*28 6/6 or 6/7
  • No previous anti-cancer therapy

You may not qualify if:

  • Pregnancy or breast-feeding women
  • Serious medical illness
  • Baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10\^9/L, Hb≥90g/L, PLT≥100×10\^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
  • DPD deficiency
  • UGT1A1\*28 7/7

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor biopsy samples and peripheral blood samples are collected before neoadjuvant therapy.

MeSH Terms

Conditions

Rectal NeoplasmsAdenocarcinoma

Interventions

Radiationcapecitabine-irinotecan combination

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

  • Ji Zhu, MD

    Fudan University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ji Zhu, MD

CONTACT

+86-2164175590leo.zhu@126.com

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Professor

Study Record Dates

First Submitted

December 30, 2019

First Posted

January 14, 2020

Study Start

December 1, 2019

Primary Completion

December 31, 2020

Study Completion

December 31, 2021

Last Updated

January 14, 2020

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)