Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for pMMR/MSS Locally Advanced Mid-low Rectal Cancer

NCT06056804 | Active Not Recruiting Phase 2

• 1 other identifier: ZDX+PD-1-LARC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open, prospective, multi-center, single-arm phase II clinical study assessing the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin in patients with pMMR/MSS locally advanced middle and low rectal cancer.

Conditions

Locally Advanced Rectal Cancer

Keywords

pMMR/MSS; locally Advanced Rectal Cancer; PD-1; neoadjuvant; chemoradiation; Thymalfasin

Outcome Measures

Primary Outcomes (1)

• CR rate

  complete response rate, If patients achieved cCR after neoadjuvant therapy or were confirmed pCR after TME, they were considered as complete response (CR). pCR was defined as no residual tumor cells on the histologic examination of surgical specimens according to AJCC 8th edition. cCR was defined according to the Memorial Sloan Kettering Cancer Center (MSKCC) standard.

  from preoperative to 10 days postoperative

Secondary Outcomes (7)

• TRAE

  from commencing of treatment to the 30th day after surgery

• 30-day incidence of postoperative complications

  within 30 days after surgery

• ORR

  before surgery

• 3-y DFS rate

  3 years

• NAR score

  within 10 days after surgery

Other Outcomes (5)

• The expression of CD68

  up to 3 months after surgery

• The expression of CD86

  up to 3 months after surgery

• The expression of CD163

  up to 3 months after surgery

Study Arms (1)

cCRT+tislelizumab+thymalfasin

EXPERIMENTAL

A total of 20 pMMR/MSS locally advanced middle and low rectal cancer patients will receive long-course concurrent chemoradiotherapy combined with 3 cycles of tislelizumab and 11 weeks of thymalfasin therapy.

Drug: capecitabine; Drug: tislelizumab; Drug: thymalfasin; Radiation: long-term radiotherapy

Interventions

capecitabine DRUG

825-1000mg/m2,po,bid

cCRT+tislelizumab+thymalfasin

tislelizumab DRUG

200mg,iv.gtt,q3w

cCRT+tislelizumab+thymalfasin

thymalfasin DRUG

4.8mg,sc,biw

cCRT+tislelizumab+thymalfasin

long-term radiotherapy RADIATION

50 Gy/25 f, 2 Gy/day

cCRT+tislelizumab+thymalfasin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who were fully informed of the study and voluntarily signed the informed consent form;
• Patients with rectal cancers must satisfied all the following conditions:
• \) Stage II/III LARC (cT3-4aN0M0 and cT1-4aN1-2M0); 2) Tumor distal located ≤ 10 cm from anal verge (MRI diagnosed); 3) pMMR or MSS confirmed by immunohistochemistry or genetic test. 3.Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1; 4. Physical and viscera function of patients can withstand major abdominal surgery; 5.Patients are willing and able to follow the study protocol during the study 6.Patients give consent to the use of pathological specimens for study 7.Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose.

You may not qualify if:

• Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time;
• Patients underwent major surgery within 4 weeks prior to study treatment;
• Patients have any condition affects the absorption of capecitabine through gastrointestinal tract;
• Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
• Patients who are allergic to any of the ingredients under study;
• Patients with severe concomitant diseases with estimated survival ≤ 5 years;
• Patients with present or previous moderate or severe liver and kidney damage presently or previously;
• Patients have received other study medications or any immunotherapy currently or in the past;
• Patients preparing for or previously received organ or bone marrow transplant;
• Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy;
• Patients with congenital or acquired immune deficiency (such as HIV infection);
• If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance;
• Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities.
• Pregnant or lactating women
• Criteria for Withdrawal:

Sponsors & Collaborators

• Beijing Friendship Hospital: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (2)

Beijing Friendship Hospital,Capital Medical University

Beijing, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Related Publications (5)

• Amin, M. B. et al. AJCC cancer staging manual. (New York: Springer. 252-274 2017)

  BACKGROUND

• Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699.

  PMID: 33264544 BACKGROUND

• King RS, Tuthill C. Evaluation of thymosin alpha 1 in nonclinical models of the immune-suppressing indications melanoma and sepsis. Expert Opin Biol Ther. 2015;15 Suppl 1:S41-9. doi: 10.1517/14712598.2015.1008446. Epub 2015 Feb 2.

  PMID: 25643200 BACKGROUND

• Danielli R, Cisternino F, Giannarelli D, Calabro L, Camerini R, Savelli V, Bova G, Dragonetti R, Di Giacomo AM, Altomonte M, Maio M. Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy. Expert Opin Biol Ther. 2018 Jul;18(sup1):77-83. doi: 10.1080/14712598.2018.1494717.

  PMID: 30063847 BACKGROUND

• Renga G, Bellet MM, Pariano M, Gargaro M, Stincardini C, D'Onofrio F, Mosci P, Brancorsini S, Bartoli A, Goldstein AL, Garaci E, Romani L, Costantini C. Thymosin alpha1 protects from CTLA-4 intestinal immunopathology. Life Sci Alliance. 2020 Aug 14;3(10):e202000662. doi: 10.26508/lsa.202000662. Print 2020 Oct.

  PMID: 32817121 BACKGROUND

MeSH Terms

Interventions

Capecitabine; tislelizumab; Thymalfasin

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thymosin; Thymus Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: neoadjuvant chemoradiotherapy combined with PD-1 monoclonal antibody and thymalfasin

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: September 28, 2023
• Study Start: January 3, 2024
• Primary Completion: December 1, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 2, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)