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

Locally Advanced Rectal Cancer Clinical Trial

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 (POLARSTAR Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05245474
• Other study ID #: BFH-POLARSTAR
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: September 1, 2029

Study information

• Verified date: January 2024
• Source: Beijing Friendship Hospital
• Contact: Zhongtao Zhang, M.D.
• Phone: +8613801060364
• Email: zhangzht[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: September 1, 2029
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chaoyang Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Xuanwu Hospital, Capital Medical University	Beijing	Beijing

Sponsors (9)

Lead Sponsor	Collaborator
Beijing Friendship Hospital	BeiGene, Beijing Chao Yang Hospital, Beijing Hospital, Peking Union Medical College Hospital, Peking University Cancer Hospital & Institute, Peking University First Hospital, Peking University People's Hospital, Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pCR rate	pathological complete response rate	within 10 days after surgery
Secondary	NAR score	neoadjuvant rectal score	within 10 days after surgery
Secondary	2-y OS rate	2-year overall survival rate	2 year
Secondary	2-y DFS rate	2-year disease free survival rate	2 year
Secondary	3-y OS rate	3-year overall survival rate	3 year
Secondary	3-y DFS rate	3-year disease free survival rate	3 year
Secondary	5-y OS rate	5-year overall survival rate	5 year
Secondary	5-y DFS rate	5-year disease free survival rate	5 year
Secondary	median OS time	median length (in months) of overall survival period	0~60 months
Secondary	median DFS time	median length (in months) of disease free survival period	0~60 months
Secondary	R0 resection rate	rate of R0 resection	within 10 days after surgery
Secondary	sphincter preserving rate	proportion of patients with preserved anal sphincter	instantly after surgery
Secondary	nearly pCR rate	nearly pathological complete response rate	within 10 days after surgery
Secondary	ORR	objective response rate	before surgery
Secondary	immune-related adverse event rate	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
Secondary	Grade 3+ immune-related adverse event rate	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
Secondary	treatment-related adverse event rate	adverse event rate that is deemed to be associated with all treatments	from commencing of treatment to the 30th day after surgery
Secondary	Grade 3+ treatment-related adverse event rate	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
Secondary	cCR rate	clinical complete response rate	before surgery
Secondary	incidence rate of surgical complications	incidence rate of surgical complications within 30 days after surgery	within 30 days after surgery
Secondary	incidence rate of Grade 3+ surgical complications	incidence rate of Grade 3+ surgical complications within 30 days after surgery	within 30 days after surgery
Secondary	quality of life score	quality of life score during the 5 years after surgery, multiple timepoint assessment	during the 5 years after surgery

External Links

•   Study protocol was published as an abstract on 2022 ESMO Congress