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

January 9, 2024 updated by: Zhongtao Zhang, Beijing Friendship Hospital

Efficacy and Safety of Neoadjuvant Long-course Chemoradiation Plus Tislelizumab in Mid-low Locally Advanced Rectal Cancer: a Phase II, Multi-center, Open-label, Randomized Controlled Trial (POLARSTAR Trial)

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).

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.

Detailed Description

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.

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.
186

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 2

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 Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • Peking University People's Hospital
        • Contact:
        • Principal Investigator:
          • Yingjiang Ye, M.D.
        • Sub-Investigator:
          • Zhidong Gao, M.D.
        • Sub-Investigator:
          • Shuang Cao, M.D.
      • Beijing, Beijing, China, 100050
        • Recruiting
        • Beijing Friendship hospital, Capital Medical University
        • Contact:
        • Principal Investigator:
          • Zhongtao Zhang, M.D.
        • Sub-Investigator:
          • Yingchi Yang, M.D.
        • Sub-Investigator:
          • Hongwei Yao, M.D.
        • Sub-Investigator:
          • Kai Pang, M.D.
      • Beijing, Beijing, China
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:
        • Principal Investigator:
          • Yi Xiao, M.D.
        • Principal Investigator:
          • Guole Lin, M.D.
        • Sub-Investigator:
          • Jiaolin Zhou, M.D.
        • Sub-Investigator:
          • Danyang Zhu, M.D.
      • Beijing, Beijing, China
        • Recruiting
        • Peking University First Hospital
        • Contact:
        • Principal Investigator:
          • Xin Wang, M.D.
        • Sub-Investigator:
          • Yingchao Wu, M.D.
      • Beijing, Beijing, China
        • Completed
        • Beijing Cancer Hospital
      • Beijing, Beijing, China
        • Completed
        • Beijing Chaoyang Hospital, Capital Medical University
      • Beijing, Beijing, China
        • Completed
        • Beijing Hospital
      • Beijing, Beijing, China
        • Completed
        • Xuanwu Hospital, Capital Medical University

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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: Randomized
  • Interventional Model: Parallel 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: 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.
Combination product: 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
Experimental: 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.
Combination product: 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
Active Comparator: 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.
Combination product: 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

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
pCR rate
Time Frame: within 10 days after surgery
pathological complete response rate
within 10 days after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
NAR score
Time Frame: within 10 days after surgery
neoadjuvant rectal score
within 10 days after surgery
2-y OS rate
Time Frame: 2 year
2-year overall survival rate
2 year
2-y DFS rate
Time Frame: 2 year
2-year disease free survival rate
2 year
3-y OS rate
Time Frame: 3 year
3-year overall survival rate
3 year
3-y DFS rate
Time Frame: 3 year
3-year disease free survival rate
3 year
5-y OS rate
Time Frame: 5 year
5-year overall survival rate
5 year
5-y DFS rate
Time Frame: 5 year
5-year disease free survival rate
5 year
median OS time
Time Frame: 0~60 months
median length (in months) of overall survival period
0~60 months
median DFS time
Time Frame: 0~60 months
median length (in months) of disease free survival period
0~60 months
R0 resection rate
Time Frame: within 10 days after surgery
rate of R0 resection
within 10 days after surgery
sphincter preserving rate
Time Frame: instantly after surgery
proportion of patients with preserved anal sphincter
instantly after surgery
nearly pCR rate
Time Frame: within 10 days after surgery
nearly pathological complete response rate
within 10 days after surgery
immune-related adverse event rate
Time Frame: from commencing of PD-1 inhibition to the 30th day after surgery
adverse event rate that is deemed to be associated with PD-1 inhibition
from commencing of PD-1 inhibition to the 30th day after surgery
Grade 3+ immune-related adverse event rate
Time Frame: from commencing of PD-1 inhibition to the 30th day after surgery
adverse event (above Grade 3) rate that is deemed to be associated with PD-1 inhibition
from commencing of PD-1 inhibition to the 30th day after surgery
treatment-related adverse event rate
Time Frame: from commencing of treatment to the 30th day after surgery
adverse event rate that is deemed to be associated with all treatments
from commencing of treatment to the 30th day after surgery
Grade 3+ treatment-related adverse event rate
Time Frame: from commencing of treatment to the 30th day after surgery
adverse event (above Grade 3) rate that is deemed to be associated with all treatments
from commencing of treatment to the 30th day after surgery
cCR rate
Time Frame: before surgery
clinical complete response rate
before surgery
ORR
Time Frame: before surgery
objective response rate
before surgery
incidence rate of surgical complications
Time Frame: within 30 days after surgery
incidence rate of surgical complications within 30 days after surgery
within 30 days after surgery
incidence rate of Grade 3+ surgical complications
Time Frame: within 30 days after surgery
incidence rate of Grade 3+ surgical complications within 30 days after surgery
within 30 days after surgery
quality of life score
Time Frame: during the 5 years after surgery
quality of life score during the 5 years after surgery, multiple timepoint assessment
during the 5 years after surgery

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.
Beijing Friendship Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Peking University First Hospital
Peking University People's Hospital
Peking Union Medical College Hospital
Peking University Cancer Hospital & Institute
Xuanwu Hospital, Beijing
Beijing Chao Yang Hospital
Beijing Hospital
BeiGene

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zhongtao Zhang, Beijing Friendship Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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 (Actual)

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.
April 1, 2022

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.
March 1, 2024

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.
September 1, 2029

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).
February 6, 2022

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.
February 6, 2022

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.
February 18, 2022

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.
January 10, 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.
January 9, 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.
January 1, 2024

More Information

Terms related to this study

Keywords

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.
  • BFH-POLARSTAR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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

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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