NCT05245474

Brief Summary

This is a phase II/III, multi-center, open-label, 3-arm, randomized controlled trial assessing the efficacy and safety of neoadjuvant long-course chemoradiation combined with Tislelizumab (PD-1 inhibitor) and subsequent TME surgery, by comparing assorted endpoints between two experiment groups (Experiment group 1: chemoradiation+concurrent PD-1 inhibitor; Experiment group 2: chemoradiation+sequential PD-1 inhibitor) with a control group (chemoradiation only).

Trial Health

77
On Track

Trial Health Score

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

Enrollment
186

participants targeted

Target at P75+ for phase_2

Timeline
40mo left

Started Apr 2022

Longer than P75 for phase_2

Geographic Reach
1 country

8 active sites

Status
recruiting

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 Progress56%
Apr 2022Sep 2029

First Submitted

Initial submission to the registry

February 6, 2022

Completed
12 days until next milestone

First Posted

Study publicly available on registry

February 18, 2022

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2022

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2024

Completed
5.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2029

Expected
Last Updated

January 10, 2024

Status Verified

January 1, 2024

Enrollment Period

1.9 years

First QC Date

February 6, 2022

Last Update Submit

January 9, 2024

Conditions

Locally Advanced Rectal Cancer

Keywords

LARCradiationchemoradiationPD-1Tislelizumabneoadjuvantrandomizedcontrolled

Outcome Measures

Primary Outcomes (1)

  • pCR rate

    pathological complete response rate

    within 10 days after surgery

Secondary Outcomes (21)

  • NAR score

    within 10 days after surgery

  • 2-y OS rate

    2 year

  • 2-y DFS rate

    2 year

  • 3-y OS rate

    3 year

  • 3-y DFS rate

    3 year

  • +16 more secondary outcomes

Study Arms (3)

CRT+concurrent PD-1 inhibition (Experiment Arm 1)

EXPERIMENTAL

Long-course chemoradiation plus PD-1 inhibition (Tislelizumab 200mg, 3 times, 3-week interval) starting on Day 8 of radiation therapy. TME surgery is scheduled in 8\~12 weeks after completion of radiation.

Combination Product: Long-course chemoradiation, with or without Tislelizumab (PD-1 inhibitor)

CRT+sequential PD-1 inhibition (Experiment Arm 2)

EXPERIMENTAL

Long-course chemoradiation plus PD-1 inhibition (Tislelizumab 200mg, 3 times, 3-week interval) starting on Day 15 after completion of radiation therapy. TME surgery is scheduled in 8\~12 weeks after completion of radiation.

Combination Product: Long-course chemoradiation, with or without Tislelizumab (PD-1 inhibitor)

CRT without PD-1 inhibition (Control Arm)

ACTIVE COMPARATOR

Long-course chemoradiation plus PD-1 inhibition with no PD-1 inhibition. TME surgery is scheduled in 6\~12 weeks after completion of radiation.

Combination Product: Long-course chemoradiation, with or without Tislelizumab (PD-1 inhibitor)

Interventions

Long-course chemoradiation, with or without Tislelizumab (PD-1 inhibitor)COMBINATION_PRODUCT

Tislelizumab is added to long-course chemoradiation (CRT) of LARC patients, with CRT+concurrent Tislelizumab for Arm 1, CRT+sequential Tislelizumab for Arm 2, and CRT only for Arm 3

CRT without PD-1 inhibition (Control Arm)CRT+concurrent PD-1 inhibition (Experiment Arm 1)CRT+sequential PD-1 inhibition (Experiment Arm 2)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • aged 18\~75
  • ECOG score 0\~2
  • biopsy diagnosed rectal adenocarcinoma, distal margin within 10cm to anal verge
  • no distant metastasis, staged II/III (T4b excluded) by MRI
  • maximum diameter of rectal cancer lesion≥10mm according to baseline CT or MRI (i.e. a "measurable lesion" as per RECIST 1.1 criteria)
  • willing and able to comply with study protocol
  • consent to the use of blood and tissue specimens for study
  • no history of previous anti-tumor treatment (e.g. radiation, chemo, immuno, bio, herbal, etc.)
  • no disorders/diseases of immune system (e.g. systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, autoimmune hemolytic anemia, hyperthyroidism/hypothyroidism, ulcerative colitis, autoimmune hemolytic anemia, HIV infection, etc.)
  • no significant dysfunction of major viscera (e.g. heart, lung, liver, kidney, etc.)
  • no jaundice or gastrointestinal obstruction
  • no acute/ongoing infection
  • no significant irregularities in blood routine test and biochemical test results, particular requirements include: neutrophils≥1.5×109/L, HGB≥80g/L, platelet≥100×109/L, serum creatinine≤1.5×ULN, total bilirubin≤1.5×ULN, ALT、AST≤2.5×ULN
  • no social or mental disorder

You may not qualify if:

  • multiple cancers, or with concomitant malignant tumors besides rectal cancer
  • having received any anti-cancer treatment (surgery, drugs, etc.) in the past 5 years
  • history of recent major surgery
  • with condition that affects the absorption of capecitabine via gastrointestinal tract (e.g. inability to swallow, nausea, vomiting, chronic diarrhea, etc.)
  • with uncontrolled, severe, concomitant diseases of any sort
  • allergic to any of the ingredients under study
  • estimated survival ≤ 5 years due to any reason
  • preparing for or having previously received organ or bone marrow transplant
  • for patients with history of disorder of central nervous system, investigator discretion is required as to whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance
  • with other conditions/issues that may affect the study results or cause the study treatment to be terminated halfway (e.g. alcoholism, drug abuse, etc.)
  • pregnant or lactating women, or women intending on conception during treatment period

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

COMPLETED

Beijing Chaoyang Hospital, Capital Medical University

Beijing, Beijing Municipality, China

COMPLETED

Beijing Hospital

Beijing, Beijing Municipality, China

COMPLETED

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, China

RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, China

RECRUITING

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

COMPLETED

Related Publications (4)

  • Pang K, Yang Y, Zhao P, Wu G, Li J, Gao J, Yao H, Yang Y, Zhang Z. Adding immune checkpoint blockade to neoadjuvant chemoradiation in locally advanced rectal cancer. Br J Surg. 2022 Oct 14;109(11):1178-1179. doi: 10.1093/bjs/znac298. No abstract available.

    PMID: 36001602BACKGROUND

  • Pang K, Sun P, Liu X, Yang D, Zhao P, Huang Y, Cao S, Gao Y, Chen G, Yu H, Duan L, Yang Y, Zhang Z. Development of the rationale of a personalized cancer vaccine based on the in situ vaccine effect of radiotherapy: a mechanistic study of the POLARSTAR trial. Cancer Immunol Immunother. 2025 Nov 12;74(12):369. doi: 10.1007/s00262-025-04229-3.

    PMID: 41222702DERIVED

  • Yang Y, Pang K, Lin G, Liu X, Gao J, Zhou J, Xu L, Gao Z, Wu Y, Li A, Han J, Wu G, Wang X, Li F, Ye Y, Zhang J, Chen G, Wang H, Kong Y, Wu A, Xiao Y, Yao H, Zhang Z. Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial. Nat Med. 2025 Feb;31(2):449-456. doi: 10.1038/s41591-024-03360-5. Epub 2025 Jan 6.

    PMID: 39762418DERIVED

  • Pang K, Yang Y, Tian D, Zeng N, Cao S, Ling S, Gao J, Zhao P, Wang H, Kong Y, Zhang J, Chen G, Deng W, Bai Z, Jin L, Wu G, Zhu D, Wang Y, Zhou J, Wu B, Lin G, Xiao Y, Gao Z, Ye Y, Wang X, Li A, Han J, Yao H, Yang Y, Zhang Z. Long-course chemoradiation plus concurrent/sequential PD-1 blockade as neoadjuvant treatment for MMR-status-unscreened locally advanced rectal cancer: protocol of a multicentre, phase 2, randomised controlled trial (the POLAR-STAR trial). BMJ Open. 2023 Sep 12;13(9):e069499. doi: 10.1136/bmjopen-2022-069499.

    PMID: 37699634DERIVED

Related Links

MeSH Terms

Interventions

Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesAntineoplastic Agents, ImmunologicalAntineoplastic AgentsTherapeutic Uses

Study Officials

  • Zhongtao Zhang

    Beijing Friendship Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhongtao Zhang, M.D.

CONTACT

+8613801060364zhangzht@ccmu.edu.cn

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Masking Details
Masking is not practically possible
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director

Study Record Dates

First Submitted

February 6, 2022

First Posted

February 18, 2022

Study Start

April 1, 2022

Primary Completion

March 1, 2024

Study Completion (Estimated)

September 1, 2029

Last Updated

January 10, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Export of individual patient data is a sensitive issue according to current Chinese laws

Locations

CN(8)