Combining chemoradiation with PD-1 blockade for advanced rectal cancer treatment

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 study is testing if combining a new immune therapy with standard treatment helps people with advanced rectal cancer do better than just using the standard treatment alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 186 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing Friendship Hospital (Academic / other)
• Drugs / interventions: radiation, Tislelizumab, immunotherapy
• Locations: 8 sites (Beijing, Beijing Municipality and 7 other locations)
• Trial ID: NCT05245474 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness and safety of neoadjuvant long-course chemoradiation combined with Tislelizumab, a PD-1 inhibitor, in patients with mid-low locally advanced rectal cancer. Participants aged 18-75 will be randomly assigned to one of three groups: chemoradiation with concurrent PD-1 inhibitor, chemoradiation with sequential PD-1 inhibitor, or chemoradiation alone. The study aims to assess various endpoints, including the rate of pathological complete response (pCR) and long-term outcomes such as disease-free survival (DFS) and overall survival (OS). The trial will involve multiple centers and a total of 186 participants, with data analyzed using intention-to-treat methods.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed rectal adenocarcinoma, staged II/III, and no distant metastasis.

Not a fit: Patients with a history of immune diseases or prior anti-tumor treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with locally advanced rectal cancer.

How similar studies have performed: While similar approaches have been explored, this specific combination of chemoradiation and PD-1 blockade is relatively novel and has not been extensively tested.

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.)
* 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

Where this trial is running

Beijing, Beijing Municipality and 7 other locations

• Beijing Friendship Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (Completed)
• Beijing Chaoyang Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Completed)
• Beijing Hospital — Beijing, Beijing Municipality, China (Completed)
• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Peking University First Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Peking University People's Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Xuanwu Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Completed)

Study contacts

• Principal investigator: Zhongtao Zhang — Beijing Friendship Hospital
• Study coordinator: Zhongtao Zhang, M.D.

Conditions Locally Advanced Rectal Cancer; LARC; radiation; chemoradiation; PD-1; Tislelizumab; neoadjuvant; randomized