Pucotenlimab Plus Radiotherapy and Chemotherapy for Neoadjuvant Treatment of Locally Advanced Rectal Cance(PUCRT)

NCT06770270 | Recruiting Phase 2

• 1 other identifier: 2024-0270
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer is a common gastrointestinal tumor, with rising incidence in China. Rectal cancer accounts for nearly half of new cases, and many patients are diagnosed at a locally advanced stage. Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment, but only 20-30% achieve a complete response, with many experiencing recurrence or metastasis. Immunotherapy, particularly PD-1/PD-L1 inhibitors, has shown promise in improving outcomes, especially in dMMR/MSI-H patients. However, most rectal cancer patients have MSS, where combining immunotherapy with nCRT has shown moderate success in clinical trials. This project aims to explore the safety and efficacy of PD-1 inhibitor (pucotenlimab) combined with nCRT for locally advanced rectal cancer, potentially offering new treatment options.

Conditions

Rectal Cancer

Keywords

rectal cancer; neoadjuvant therapy; immunotherapy; radiotherapy

Outcome Measures

Primary Outcomes (2)

• The rate of cCR

  The cCR assessment is defined by the fulfillment of the following three criteria: 1. Digital rectal examination of the original tumor area shows normal findings, with no palpable tumor masses. 2. Endoscopy reveals white, flat mucosal scars accompanied by surrounding capillary ectasia, without evidence of tumor ulcers or nodules; mucosal biopsy results are negative for cancer cells. 3. Contrast-enhanced MRI of the rectum shows: On T2-weighted images, only low signal intensity (dark on T2) is present without intermediate T2 signal intensity, and there are no signs of enlarged lymph nodes. there is no visible signal on diffusion-weighted (DW) images.

  From enrollment to the end of treatment at 12 weeks

• The rate of pCR

  The definition of pCR is that after surgery, in the pathological evaluation of the resected rectal cancer lesion, mesorectum, and regional lymph node samples, there are no visible tumor cells under the microscope. Tumor cells refer to viable tumor cells, excluding degenerated or necrotic cells. Pools of acellular mucin should not be assessed as residual tumor.

  From enrollment to the end of treatment at 16 weeks

Secondary Outcomes (6)

• The rate of TRG0

  From enrollment to the end of treatment at 16 weeks

• The rate of R0 resection

  From enrollment to the end of treatment at 16 weeks

• Adverse events

  From enrollment to the end of treatment at 3 years

• Surgical safety

  From enrollment to the end of treatment at 3 years

• Event-Free Survival

  From enrollment to the end of treatment at 3 years

Study Arms (1)

A

EXPERIMENTAL

Pucotenlimab Plus Radiotherapy and Chemotherapy for Neoadjuvant Treatment

Drug: Pucotenlimab

Interventions

Pucotenlimab DRUG

Pucotenlimab combined with long-course concurrent chemoradiotherapy, followed by two cycles of pucotenlimab combined with chemotherapy, and then based on tumor response, TME surgery or a "watch and wait" strategy will be adopted.

A

Eligibility Criteria

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

You may qualify if:

• The patient voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up;
• Age 18-75 years, inclusive of 18 and 75 years, both males and females are eligible;
• Histologically confirmed and evaluated as locally advanced rectal adenocarcinoma (confirmed by MRI): cT3 or higher; or cN+;
• MRI confirms that the lower edge of the tumor is ≤10 cm from the anal verge;
• No prior anti-tumor treatment for rectal cancer (except for traditional Chinese medicine treatments);
• ECOG score of 0-1;
• Major organs or functions meet the following criteria (within 2 weeks before the test, no use of any blood components or growth factors for correction is allowed):
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelets ≥100×10\^9/L; Hemoglobin ≥10 g/dL; Serum albumin ≥3.0 g/dL; Total bilirubin ≤ ULN, ALT, AST, and/or AKP ≤2.5 × ULN; Serum creatinine ≤ ULN or creatinine clearance rate ≥60 mL/min; International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ ULN;
• Women of childbearing potential must agree to abstain from heterosexual intercourse or use reliable and effective contraception from the time of signing the informed consent form until at least 6 months after the last dose of study drug. A serum HCG test must be negative within 7 days before starting treatment, and the woman must not be breastfeeding. A woman is considered of childbearing potential if she has had menstruation, has not reached postmenopausal status (absence of menstruation for ≥12 consecutive months without any other cause), and has not undergone sterilization surgery (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy);
• Male patients with female partners of childbearing potential must agree to abstain from intercourse or use reliable and effective contraception from the time of signing the informed consent form until at least 6 months after the last dose of study drug. Male patients must also agree not to donate sperm during this period. Male patients with pregnant partners should use a condom, without the need for additional contraceptive methods.

You may not qualify if:

• Patients who meet any of the following criteria will not be eligible for this study:
• Patients with locally recurrent rectal cancer after previous treatment;
• Patients assessed by the investigator as having initially unresectable rectal cancer or those deemed unable to tolerate surgery;
• Clinical or imaging evidence suggests distant metastasis or positive lateral lymph nodes;
• Patients with multiple colorectal cancer lesions;
• Clinical or imaging evidence suggests bowel obstruction or perforation, or the investigator evaluates a high risk of perforation or bleeding;
• Factors deemed by the investigator to make the patient unsuitable for long-course radiotherapy;
• Severe cardiovascular or cerebrovascular diseases, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, or significant vascular disease (such as an aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to enrollment; poorly controlled cardiac symptoms or diseases, such as unstable angina, NYHA class II or higher heart failure, left ventricular ejection fraction \<50% by echocardiography, or severe arrhythmias not controlled by medication;
• History of active pulmonary tuberculosis detected by medical history or CT, active pulmonary tuberculosis within 1 year before enrollment, or a history of active tuberculosis more than 1 year ago that was not properly treated;
• Major surgery within 3 months before starting study treatment (major surgery is defined as surgery performed under general anesthesia); presence of non-healing wounds (severe, non-healing or dehiscent), active peptic ulcers, or untreated fractures;
• Difficulty swallowing or other factors affecting oral medication use;
• Contraindications to MRI;
• Active autoimmune disease or history of autoimmune diseases (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism \[patients controlled by thyroid hormone replacement therapy can be included\]); patients with skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia), controlled type 1 diabetes treated with insulin, and childhood asthma that has fully resolved and requires no intervention in adulthood may be included (patients requiring bronchial dilation for asthma cannot be included);
• History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation;
• Severe infections within 4 weeks before the first use of the study drug (CTCAE \> Grade 2), such as severe pneumonia, bacteremia, or infections requiring hospitalization; active lung inflammation on baseline chest imaging, signs and symptoms of infection requiring oral or intravenous antibiotics within 2 weeks before the first use of the study drug, except for prophylactic antibiotics;

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital Of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Li Shen, M.D.

  2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haiyan Chen, Ph.D. and M.D.

CONTACT

86 0571 87783759; chenhaiyan@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: January 13, 2025
• Study Start: August 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2030
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

CN (1)