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

August 21, 2025 updated by: Zhao Ren, Ruijin Hospital

Efficacy and Safety of Short-course Radiotherapy Sequential Penpulimab in Combination With CAPEOX in the Neoadjuvant Treatment of Microsatellite Stable Locally Advanced Rectal Cancer: a Single-centre, Single-arm, Phase 2 Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Today there has been an outbreak progress in immunotherapy for tumors, where immune checkpoint inhibitors targeting PD-1/PD-L1 have been approved for the treatment of a variety of tumors, bringing long-term benefits to some patients, especially colorectal cancer and other solid tumors with dMMR/MSI-H have been identified as the best indication population for immunotherapy. However, the majority of patients presented with microsatellite stable (MSS) or pMMR status had a low response rate to immunotherapy. How to improve the response to immunotherapy in these patients has been a challenge in the field of colorectal cancer immunotherapy. A number of preclinical and small clinical studies have identified immunotherapy in combination with other treatments such as chemotherapy, radiotherapy, anti-angiogenic drugs and targeted therapies as potentially viable options to overcome immune resistance and improve the outcome of MSS colorectal cancer. Preclinical and small clinical studies have demonstrated that radiotherapy may induce antigen release from tumors with low neoantigen load and activate dendritic cells, thereby activating CD8+ T lymphocyte-mediated anti-cancer immune responses. In patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy can increase PD-L1 expression in tumor cells, suggesting that the combination of radiotherapy and PD-1/PD-L1 inhibitors may have a synergistic effect. To further improve the treatment outcomes of locally advanced rectal cancer, we designed an exploratory observational study to observe the efficacy and safety of a regimen of short-course radiotherapy combined with chemotherapy and the addition of the PD-1 monoclonal antibody in locally advanced rectal cancer, and to initially explore the feasibility a watch-and-wait strategy for patients with rectal cancer who have reached pCR.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • None Selected
      • Shanghai, None Selected, China, 200025
        • Recruiting
        • Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Informed consent
  • 18 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

Exclusion Criteria:

  • 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
  • Other acute or chronic diseases, mental disorders, or laboratory test abnormalities that may result in: increasing the risk associated with research participation or drug administration, or interfering with the interpretation of the results of the study, and the patient was classified as not eligible to participate in this study according to the judgment of the researchers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SCRT sequential Penpulimab in combination with CAPEOX
  • 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
5×5Gy in Week 1
Drug: Penpulimab
Apply once in the first week, then every 3 weeks from the third week for four cycles
Other Names:
  • PD-1 monoclonal antibody
Drug: CAPEOX
Apply every 3 weeks from week 3 for 4 cycles
Other Names:
  • Capecitabine and oxaliplatin
Procedure: TME surgery
Patient will receive radical rectal cancer surgery

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological complete remission rate (pCR)
Time Frame: One month after surgery
The proportion of complete remissions detected by postoperative pathological examination (%)
One month after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clinical complete remission rate (cCR)
Time Frame: Three weeks after neoadjuvant therapy
The proportion of complete remissions detected by imaging, endoscopy and digital rectal examination (%)
Three weeks after neoadjuvant therapy
Objective response rate (ORR)
Time Frame: One month after surgery
Sum of proportion in complete and partial remission (%)
One month after surgery
3-year disease free survival rate (3y-DFS)
Time Frame: 36 months after surgery
3-year disease free survival rate estimated based on Kaplan-Meier method
36 months after surgery
R0 resection rate
Time Frame: One month after surgery
Histologically complete resection rate (%)
One month after surgery
Sphincter preservation rate
Time Frame: One month after surgery
The proportion of low rectal cancer patients retaining the sphincter in radical surgery (%)
One month after surgery
Early morbidity rate
Time Frame: 30 days after surgery
Morbidity rate 30 days after surgery (%)
30 days after surgery
Number and severity of adverse events
Time Frame: 36 months after surgery
Number and severity of adverse events using CTCAE V5.0
36 months after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ruijin Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ren Zhao, MD, PHD, Ruijin Hospitlal , Shanghai Jiaotong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 6, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 8, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SPARC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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