SCRT Sequential Penpulimab in Combination With CAPEOX in the Neoadjuvant Treatment of MSS Locally Advanced Rectal Cancer

NCT05576480 | Recruiting Phase 2 DMC

• 1 other identifier: SPARC
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this phase 2 study is to learn about the efficacy and safety of short-course radiotherapy (SCRT) sequential Penpulimab in combination with CAPEOX in the neoadjuvant treatment of microsatellite stable (MSS) locally advanced rectal cancer. The main question it aims to answer is the role of immune checkpoint inhibitors in the neoadjuvant treatment of MSS rectal cancer. Participants will receive neoadjuvant treatment of SCRT sequential Penpulimab in combination with CAPEOX. Participants will undergo a clinical re-staging assessment at the end of neoadjuvant therapy to determine whether to adopt a watch-and-wait strategy or undergo radical surgery.

Conditions

Rectal Cancer; Locally Advanced

Keywords

Immunotherapy; Neoadjuvant Treatment; Locally Advanced Rectal Cancer; Microsatellite stable

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission rate (pCR)

  The proportion of complete remissions detected by postoperative pathological examination (%)

  One month after surgery

Secondary Outcomes (7)

• Clinical complete remission rate (cCR)

  Three weeks after neoadjuvant therapy

• Objective response rate (ORR)

  One month after surgery

• 3-year disease free survival rate (3y-DFS)

  36 months after surgery

• R0 resection rate

  One month after surgery

• Sphincter preservation rate

  One month after surgery

Study Arms (1)

SCRT sequential Penpulimab in combination with CAPEOX

EXPERIMENTAL

* Short-course radiotherapy (SCRT) + one dose of immunotherapy in week 1：Radiotherapy once daily at 5Gy, D1-D5 (5×5Gy); Penpulimab, 200mg, intravenous for 60±5min, D6 or D7. * Rest at week 2, 4 cycles of chemotherapy (CAPEOX) + immunotherapy from week 3 in cycles of 3 weeks: Capecitabine, 1000 mg/m2 orally, administered twice daily, D1-D14 per cycle; Oxaliplatin, 135 mg/m2, intravenous \>2h, administered every cycle D1; Penpulimab, 200 mg, administered intravenously for 60 ± 5 min every cycle D1. * Clinical re-staging assessment at the end of neoadjuvant therapy allows for a watch-and-wait strategy if cCR is achieved. If any residual lesions remained, radical rectal cancer surgery would be performed at least 2 weeks after the last dose of capecitabine. Whether post-operative adjuvant treatment is performed and the option of post-operative adjuvant treatment is decided by the investigator.

Radiation: Short-course radiotherapy; Drug: Penpulimab; Drug: CAPEOX; Procedure: TME surgery

Interventions

Short-course radiotherapy RADIATION

5×5Gy in Week 1

SCRT sequential Penpulimab in combination with CAPEOX

Penpulimab DRUG

Apply once in the first week, then every 3 weeks from the third week for four cycles

Also known as: PD-1 monoclonal antibody

SCRT sequential Penpulimab in combination with CAPEOX

CAPEOX DRUG

Apply every 3 weeks from week 3 for 4 cycles

Also known as: Capecitabine and oxaliplatin

SCRT sequential Penpulimab in combination with CAPEOX

TME surgery PROCEDURE

Patient will receive radical rectal cancer surgery

SCRT sequential Penpulimab in combination with CAPEOX

Eligibility Criteria

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

You may qualify if:

• Informed consent
• years \< age ≤ 75 years
• ECOG score is 0-1
• Patients with pathologically confirmed rectal adenocarcinoma, assessed by MRI as mid-low rectal cancer (the lower border of the tumor is less than 10cm from the anal verge), clinical stage II-III (cT1-2N1-2M0 or T3-4N0-2M0) according to the 8th Edition of AJCC Cancer Staging Manual
• Without emergency operation due to complication (bleeding, perforation or obstruction) caused by rectal cancer
• Microsatellite Instability detection using PCR capillary electrophoresis results in MSS
• Without any anti-tumor treatment
• No distant metastasis
• Have an imaging measurable or clinically assessable lesion
• Adequate organ and bone marrow function
• Female participants of childbearing age or male participants whose sexual partners are women of childbearing age are required to use effective contraception for the entire treatment period and for 6 months after the end of the treatment period

You may not qualify if:

• Recurrent rectal cancer
• Previous treatment with pelvic radiotherapy, rectal cancer surgery, chemotherapy, targeted therapy, immune checkpoint inhibitors (including but not limited to PD-1, PD-L1, CTLA-4)
• Proven inability to receive radiotherapy or allergy to the components of Penpulimab, capecitabine, oxaliplatin or their excipients
• Intestinal obstruction due to tumor (except in patients who have received a stoma)
• History of other primary malignancies, except for: malignancies in complete remission for at least 2 years prior to enrolment and not requiring other treatment during the study period; adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease recurrence; adequately treated carcinoma in situ with no evidence of disease recurrence
• Active, known or suspected autoimmune disease or history of this disease within the previous 2 years (patients with vitiligo, psoriasis, alopecia or Graves' disease not requiring systemic treatment within the last 2 years, hypothyroidism requiring only thyroid hormone replacement therapy and type I diabetes requiring only insulin replacement therapy may be enrolled)
• Any of the following within 6 months prior to the start of treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association classification II-IV), cerebrovascular event, transient ischaemic attack, severe arrhythmia requiring drug treatment or symptomatic pulmonary embolism
• History of allogeneic organ transplantation and allogeneic haematopoietic stem cell transplantation
• Uncontrolled comorbidities including but not limited to: HIV infected; Serious infections that are active or poorly controlled clinically
• Pregnant woman or lactating woman
• Patients who have participated in another drug clinical trial within 4 weeks
• Suffering from acute or chronic active hepatitis B (HBsAg-positive and HBV DNA ≥ 200 IU/mL or ≥ 103 copies/mL) or acute or chronic active hepatitis C (HCV-positive and HCV RNA-positive)
• Received live attenuated vaccine within 4 weeks prior to enrolment or planned during the study period
• Major surgical procedure within 4 weeks prior to enrolment
• History of interstitial pneumonia

Sponsors & Collaborators

• Ruijin Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, None Selected, 200025, China

RECRUITING

Related Publications (2)

• Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. doi: 10.1016/S1470-2045(20)30555-6. Epub 2020 Dec 7.

  PMID: 33301740 BACKGROUND

• Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):501-513. doi: 10.1016/S2468-1253(17)30074-2. Epub 2017 May 4.

  PMID: 28479372 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

penpulimab; spartalizumab; Capecitabine; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Ren Zhao, MD, PHD

  Ruijin Hospitlal , Shanghai Jiaotong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ren Zhao, MD, PHD

CONTACT

+8618917762018; zhaorensurgeon@aliyun.com

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: Chief Physicion

Model Details: This is a two staged, single arm phase II trial of short-course radiotherapy sequential Penpulimab in combination with CAPEOX in the neoadjuvant treatment of microsatellite stable locally advanced rectal cancer. Twenty-three patients will be enrolled in the first phase and if the number of pathological complete remission is ≤ 3, the trial will be terminated; if \> 3, the trial will proceed to the second phase and continue to enroll up to 48 patients. Taking into account a 15% abscission rate, the total number of patients enrolled will be 55.

Study Record Dates

• First Submitted: October 8, 2022
• First Posted: October 12, 2022
• Study Start: February 6, 2023
• Primary Completion: October 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)