Clinical trial NCT06056804: Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for pMMR/MSS Locally Advanced Mid-low Rectal Cancer
Official title: Efficacy and Safety of Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin in pMMR/MSS Locally Advanced Middle and Low Rectal Cancer: An Open, Multi-center, Prospective, Single-arm Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: pMMR/MSS
locally Advanced Rectal Cancer
PD-1
neoadjuvant
chemoradiation
Thymalfasin
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
First posted: 2023-09-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: neoadjuvant chemoradiotherapy combined with PD-1 monoclonal antibody and thymalfasin
Primary purpose: TREATMENT

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.

Detailed description: This study is an open, prospective, multi-center, single-arm phase II clinical study. In this study, patients with pMMR/MSS locally advanced middle and low rectal cancer were selected as the subjects and treated with neoadjuvant treatment protocol of long-course concurrent chemoradiotherapy combined with PD-1 monoclonal antibody and thymalfasin. The primary endpoint of the study was complete response (CR) rate. The secondary end points included treatment-related adverse events (TRAEs) rate, 30-day incidence of postoperative complications, objective response rate (ORR), 3-year disease-free survival (DFS) rate, Neoadjuvant rectal cancer (NAR) score, R0 resection rate, and anal preservation rate.

Eligibility criteria: Inclusion Criteria:

1. Patients who were fully informed of the study and voluntarily signed the informed consent form;
2. Patients with rectal cancers must satisfied all the following conditions:

1) 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.

Exclusion Criteria:

1. Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time;
2. Patients underwent major surgery within 4 weeks prior to study treatment;
3. Patients have any condition affects the absorption of capecitabine through gastrointestinal tract;
4. Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
5. Patients who are allergic to any of the ingredients under study;
6. Patients with severe concomitant diseases with estimated survival ≤ 5 years;
7. Patients with present or previous moderate or severe liver and kidney damage presently or previously;
8. Patients have received other study medications or any immunotherapy currently or in the past;
9. Patients preparing for or previously received organ or bone marrow transplant;
10. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy;
11. Patients with congenital or acquired immune deficiency (such as HIV infection);
12. 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;
13. 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.
14. Pregnant or lactating women

Criteria for Withdrawal:

1. The subject withdraws informed consent;
2. The subject requests to withdraw from the study, or loses follow-up;
3. The subject demonstrates poor compliance and is unable to participate in the treatment and visits as required by the study protocol;
4. The subject experiences intolerable adverse events, and the investigator determines that continuing the study may be detrimental to the subject;
5. Other reasons, where the investigator determines it is not suitable for the subject to continue in the study.

Criteria for Study Termination:

1. There are major errors in the study protocol;
2. The study involves significant risks and is terminated following review by the ethics committee;
3. Termination requested by the sponsor or regulatory authorities.

Primary outcomes:
measure: CR rate
timeFrame: from preoperative to 10 days postoperative
Secondary outcomes:
measure: TRAE
timeFrame: from commencing of treatment to the 30th day after surgery
measure: 30-day incidence of postoperative complications
timeFrame: within 30 days after surgery
measure: ORR
timeFrame: before surgery
measure: 3-y DFS rate
timeFrame: 3 years
measure: NAR score
timeFrame: within 10 days after surgery
measure: R0 resection rate
timeFrame: within 10 days after surgery
measure: anal preservation rate
timeFrame: instantly after surgery
Other outcomes:
measure: The expression of CD68
timeFrame: up to 3 months after surgery
measure: The expression of CD86
timeFrame: up to 3 months after surgery
measure: The expression of CD163
timeFrame: up to 3 months after surgery
measure: The expression of CD4
timeFrame: up to 3 months after surgery
measure: The expression of CD8
timeFrame: up to 3 months after surgery
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital,Capital Medical University
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
References:
citation: Amin, M. B. et al. AJCC cancer staging manual. (New York: Springer. 252-274 2017)
citation: 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.
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