Neoadjuvant Long-course Chemoradiation Plus PD-1 Blockade for Mid-low Locally Advanced Rectal Cancer

NCT ID: NCT05245474

Last Updated: 2024-01-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

186 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-01

Study Completion Date

2029-09-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This phase II, multi-center, open-label, 3-arm, randomized trial aims to recruit patients aged 18-75 years, diagnosed histologically as rectal adenocarcinoma, without metastasis (by CT), staged II/III (by MRI, T4b excluded), with distal margin within 10cm to anal verge. All patients should have no history of immune diseases, nor history of immunotherapy or radiotherapy. Sample size was thoroughly calculated to be 186. Eligible participants will be randomly assigned to Experiment Arm 1 (50.4Gy radiation, capecitabine, and anti-PD1 starting at Day 8 of radiation), Experiment Arm 2 (50.4Gy radiation, capecitabine, and anti-PD1 starting 2 weeks after completion of radiation), and Control Arm (50.4Gy radiation, capecitabine) in a 1:1:1 ratio. Randomization is stratified by different centers, with a block size of 6. For both experiment arms, Tislelizumab (anti-PD1) is scheduled to be administered at 200mg each time for 3 times, with 3-week intervals. The primary endpoint is pCR rate, and secondary endpoints include sphincter-preserving rate, adverse event rates, and DFS and OS rate at 2, 3 and 5 years post-operation. Data will be analyzed with an intention-to-treat or modified intention-to-treat approach.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Locally Advanced Rectal Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Masking is not practically possible

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

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.

Group Type EXPERIMENTAL

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

Intervention Type 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+sequential PD-1 inhibition (Experiment Arm 2)

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.

Group Type EXPERIMENTAL

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

Intervention Type 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)

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

Group Type ACTIVE_COMPARATOR

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

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

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

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* for women of child-bearing age, a negative result of serological pregnancy test is required, and effective contraception measures from inclusion till 60 days after the last dose of study drug is required

Exclusion Criteria

* 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
* having received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to inclusion
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Beijing Chao Yang Hospital

OTHER

Sponsor Role collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role collaborator

Beijing Hospital

OTHER_GOV

Sponsor Role collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role collaborator

Peking University First Hospital

OTHER

Sponsor Role collaborator

Peking University People's Hospital

OTHER

Sponsor Role collaborator

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role collaborator

BeiGene

INDUSTRY

Sponsor Role collaborator

Beijing Friendship Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Zhongtao Zhang

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Zhongtao Zhang

Role: PRINCIPAL_INVESTIGATOR

Beijing Friendship Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status COMPLETED

Beijing Chaoyang Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status COMPLETED

Beijing Hospital

Beijing, Beijing Municipality, China

Site Status COMPLETED

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status COMPLETED

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Zhongtao Zhang, M.D.

Role: CONTACT

+8613801060364

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Kai Pang, M.D.

Role: primary

86 18811792819

Danyang Zhu, M.D.

Role: primary

86 13466711222

Yingchao Wu, M.D.

Role: primary

86 13693214551

Shuang Cao, M.D.

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 36001602 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39762418 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37699634 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://doi.org/10.1016/j.annonc.2022.07.1868

Study protocol was published as an abstract on 2022 ESMO Congress

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

BFH-POLARSTAR

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.