POLAR-STAR: Phase II, Multi-center, Open-label, Randomized Trial on Efficacy and Safety of Neoadjuvant Long-course Chemoradiation Plus Tislelizumab in Mid-low Locally Advanced Rectal Cancer

Sponsor

Beijing Friendship Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05245474

Collaborator

Beijing Chao Yang Hospital (Other), Xuanwu Hospital, Beijing (Other), Beijing Hospital (Other), Peking Union Medical College Hospital (Other), Peking University First Hospital (Other), Peking University People's Hospital (Other)

120

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 two different experiment groups (combination therapy) with a control group (traditional treatment without Tislelizumab).

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Combination Product: Radiation therapy, chemotherapy and immune checkpoint inhibitor	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

Masking is not practically possible

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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: Radiation therapy, chemotherapy and immune checkpoint inhibitor Long-course chemoradiation (50.4Gy) plus Tislelizumab (concurrent and sequential)
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: Radiation therapy, chemotherapy and immune checkpoint inhibitor Long-course chemoradiation (50.4Gy) plus Tislelizumab (concurrent and sequential)
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 8~12 weeks after completion of radiation.	Combination Product: Radiation therapy, chemotherapy and immune checkpoint inhibitor Long-course chemoradiation (50.4Gy) plus Tislelizumab (concurrent and sequential)

Arm

Intervention/Treatment

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: Radiation therapy, chemotherapy and immune checkpoint inhibitor

Long-course chemoradiation (50.4Gy) plus Tislelizumab (concurrent and sequential)

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: Radiation therapy, chemotherapy and immune checkpoint inhibitor

Long-course chemoradiation (50.4Gy) plus Tislelizumab (concurrent and sequential)

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 8~12 weeks after completion of radiation.

Combination Product: Radiation therapy, chemotherapy and immune checkpoint inhibitor

Long-course chemoradiation (50.4Gy) plus Tislelizumab (concurrent and sequential)

Outcome Measures

Primary Outcome Measures

pCR rate [within 10 days after surgery]
pathological complete response rate

Secondary Outcome Measures

NAR score [within 10 days after surgery]
neoadjuvant rectal score
2-y OS rate [2 year]
2-year overall survival rate
2-y DFS rate [2 year]
2-year disease free survival rate
3-y OS rate [3 year]
3-year overall survival rate
3-y DFS rate [3 year]
3-year disease free survival rate
5-y OS rate [5 year]
5-year overall survival rate
5-y DFS rate [5 year]
5-year disease free survival rate
median OS time [0~60 months]
median length (in months) of overall survival period
median DFS time [0~60 months]
median length (in months) of disease free survival period
R0 resection rate [within 10 days after surgery]
rate of R0 resection
sphincter preserving rate [instantly after surgery]
proportion of patients with preserved anal sphincter
nearly pCR rate [within 10 days after surgery]
nearly pathological complete response rate
immune-related adverse event rate [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
Grade 3+ immune-related adverse event rate [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
treatment-related adverse event rate [from commencing of treatment to the 30th day after surgery]
adverse event rate that is deemed to be associated with all treatments
Grade 3+ treatment-related adverse event rate [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

aged 18~75
ECOG score 0~2
biopsy diagnosed rectal cancer, distal margin within 10cm to anal verge
no distant metastasis, staged II/III (T4b excluded) by MRI
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, 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 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 through 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 to be terminated halfway (e.g. alcoholism, drug abuse, etc.)
pregnant or lactating women, or women intending on conception during treatment period