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)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Locally Advanced Rectal Cancer
- Sponsor
- Beijing Friendship Hospital
- Enrollment
- 186
- Locations
- 8
- Primary Endpoint
- pCR rate
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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).
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.
Investigators
Zhongtao Zhang
Director
Beijing Friendship Hospital
Eligibility Criteria
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.)
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
Outcomes
Primary Outcomes
pCR rate
Time Frame: within 10 days after surgery
pathological complete response rate
Secondary Outcomes
- 5-y DFS rate(5 year)
- 3-y OS rate(3 year)
- NAR score(within 10 days after surgery)
- median OS time(0~60 months)
- R0 resection rate(within 10 days after surgery)
- sphincter preserving rate(instantly after surgery)
- 2-y OS rate(2 year)
- 2-y DFS rate(2 year)
- 3-y DFS rate(3 year)
- 5-y OS rate(5 year)
- median DFS time(0~60 months)
- immune-related adverse event rate(from commencing of PD-1 inhibition to the 30th day after surgery)
- Grade 3+ immune-related adverse event rate(from commencing of PD-1 inhibition to the 30th day after surgery)
- treatment-related adverse event rate(from commencing of treatment to the 30th day after surgery)
- nearly pCR rate(within 10 days after surgery)
- ORR(before surgery)
- Grade 3+ treatment-related adverse event rate(from commencing of treatment to the 30th day after surgery)
- incidence rate of surgical complications(within 30 days after surgery)
- quality of life score(during the 5 years after surgery)
- cCR rate(before surgery)
- incidence rate of Grade 3+ surgical complications(within 30 days after surgery)