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Colorectal CancerPhase 2PICCNCT03926338

Neoadjuvant Toripalimab With or Without Celecoxib in dMMR/MSI-H Colorectal Cancer

A Phase 2 study testing Neoadjuvant toripalimab plus celecoxib for 6 cycles, Neoadjuvant toripalimab monotherapy for 6 cycles and Neoadjuvant toripalimab plus celecoxib for 12 cycles in people with Colorectal Cancer and Mismatch Repair-deficient (dMMR), run by Sun Yat-sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher proportion in right colon cancer. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Neoadjuvant toripalimab plus celecoxib for 6 cycles, Neoadjuvant toripalimab monotherapy for 6 cycles and Neoadjuvant toripalimab plus celecoxib for 12 cycles
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
1 siteChina
Study dates
10 May 2019to 1 Apr 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide written informed consent.
  • Histological or cytological documentation of adenocarcinoma of the colon or rectum.
  • Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
  • Male or female subjects aged 18 to 75 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Determined CT or MRI scans (done within 14 days of registration) of the chest, abdomen and pelvis: locally advanced (cT3-4 or cN1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]).
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  • Non complicated primary tumor (obstruction, perforation, bleeding).
  • No previous any systemic anticancer therapy for colorectal cancer disease.
  • Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.

Who cannot join

  • Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
  • Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
  • Heart failure grade III/IV (NYHA-classification).
  • Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
  • Subjects with known allergy to the study drugs or to any of its excipients.
  • Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
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  • Breast- feeding or pregnant women
  • Lack of effective contraception.
  • Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
  • With any distant metastasis.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yanhong Deng, M.D. contact

86-13925106525

dengyanh@mail.sysu.edu.cn

China1 site, 1 recruiting

  • The Sixth Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510655

    Yanhong Deng, M.D., 86-13925106525, dengyanh@mail.sysu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Neoadjuvant PD-1 Blockade by Toripalimab With or Without Celecoxib in Mismatch-repair Deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC)

Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher proportion in right colon cancer. Previous studies have found that colon cancer patients with dMMR/MSI-H cannot benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and the prognosis is significantly worse than that of mismatch repair-proficient (pMMR)/microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in 《N Engl J Med》 showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy.

Anti-PD-1 neoadjuvant therapy has proven to be safe and feasible in lung cancer, bladder cancer and malignant melanoma, and can achieve more than 40% of major pathological response. However, there are no reports of anti-PD-1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to find the best multidisciplinary treatment for resectable colorectal cancer patient with the dMMR/MSI-H phenotype and to explore whether cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could further improve efficacy.

Read the detailed description

The PICC trial is an investigator-initiated, multi-cohort platform trial designed to evaluate the efficacy and safety of neoadjuvant toripalimab, with or without celecoxib, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer. Each cohort within the PICC platform was independently conducted and analyzed according to prespecified objectives.

The initial exploratory cohort, PICC-1, was originally planned to enroll 20 eligible patients to receive neoadjuvant toripalimab plus celecoxib or toripalimab alone, with the primary objective of assessing feasibility and safety. The study was amended in August 2020 to change the primary objective to evaluating whether 6 cycles of neoadjuvant toripalimab with or without celecoxib improves the pathological complete response (pCR) rate compared with historical controls, with an updated planned enrollment of 34 eligible patients, who were to be randomized 1:1 between the two treatment groups. In May 2021, an additional 16 eligible patients were included in this exploratory cohort for translational research purposes.

The study was amended in April 2022 to add a new cohort, PICC-2, which was designed to formally compare the efficacy and safety of 12 cycles of neoadjuvant toripalimab plus celecoxib versus toripalimab monotherapy in patients with dMMR or MSI-H locally advanced colorectal cancer. A total of 110 eligible patients are planned to be randomized 1:1 between the two treatment groups.

The study was amended in June 2025 to add a new cohort, PICC-3, which was designed to evaluate the 3-year event-free survival (EFS) of 12 cycles of toripalimab plus celecoxib administered as neoadjuvant or definitive therapy in patients with dMMR or MSI-H locally advanced colorectal cancer. Approximately 108 eligible patients are expected to be enrolled.

Being tested
Neoadjuvant toripalimab plus celecoxib for 6 cycles, Neoadjuvant toripalimab monotherapy for 6 cycles, Neoadjuvant toripalimab plus celecoxib for 12 cycles, Neoadjuvant toripalimab monotherapy for 12 cycles, Toripalimab plus celecoxib as neoadjuvant or definitive therapy
Medical subject headings
Colorectal Neoplasms, Turcot syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Neoadjuvant toripalimab plus celecoxib for 6 cyclesDrug

    Also called Toripalimab, Celecoxib

    Toripalimab was administered intravenously over 30 minutes at a dose of 3 mg per kilogram on day 1 of each 14-day cycle, every 2 weeks for a total of 6 cycles, and celecoxib was given orally at 200 mg twice daily from day 1 to day 14 of each cycle, followed by surgery.

  • Neoadjuvant toripalimab monotherapy for 6 cyclesDrug

    Also called Toripalimab

    Toripalimab was administered intravenously over 30 minutes at a dose of 3 mg per kilogram on day 1 of each 14-day cycle, every 2 weeks for a total of 6 cycles, followed by surgery.

  • Neoadjuvant toripalimab plus celecoxib for 12 cyclesDrug

    Also called Toripalimab, Celecoxib

    Toripalimab was administered intravenously over 30 minutes at a dose of 3 mg per kilogram on day 1 of each 14-day cycle, every 2 weeks for a total of 12 cycles, and celecoxib was given orally at 200 mg twice daily from day 1 to day 14 of each cycle, followed by surgery.

  • Neoadjuvant toripalimab monotherapy for 12 cyclesDrug

    Also called Toripalimab

    Toripalimab was administered intravenously over 30 minutes at a dose of 3 mg per kilogram on day 1 of each 14-day cycle, every 2 weeks for a total of 12 cycles, followed by surgery.

  • Toripalimab plus celecoxib as neoadjuvant or definitive therapyDrug

    Also called Toripalimab, Celecoxib

    Toripalimab was administered intravenously over 30 minutes at a dose of 3 mg per kilogram on day 1 of each 14-day cycle, every 2 weeks for a total of 12 cycles, and celecoxib was given orally at 200 mg twice daily from day 1 to day 14 of each cycle, followed by surgery or non-operative management based on restaging (non-operative management was recommended for patients with a complete clinical response).

Study groups in NCT03926338
Study groupRoleWhat they receive
PICC-1 exploratory cohortExperimentalNeoadjuvant toripalimab with or without celecoxib for 6 cycles
Receives: Drug: Neoadjuvant toripalimab plus celecoxib for 6 cycles; Drug: Neoadjuvant toripalimab monotherapy for 6 cycles
PICC-2 cohortExperimentalNeoadjuvant toripalimab with or without celecoxib for 12 cycles
Receives: Drug: Neoadjuvant toripalimab plus celecoxib for 12 cycles; Drug: Neoadjuvant toripalimab monotherapy for 12 cycles
PICC-3 cohortExperimentalToripalimab plus celecoxib as neoadjuvant or definitive therapy
Receives: Drug: Toripalimab plus celecoxib as neoadjuvant or definitive therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological complete response (pCR) rates (PICC-1 and PICC-2 cohorts)

    The proportion of patients who achieved a pCR, which was defined as the absence of residual viable tumor cells in the primary tumor and all sampled lymph nodes at surgery.

    Measured: 1 year

  2. Event-free survival (EFS) (PICC-3 cohort)

    Defined as the time from randomization until the date of one of the following events (whichever occurred first): disease progression that precluded surgery, local R2 resection, local recurrence after an R0/1 resection, distant metastases, a new primary colorectal cancer, or death from any cause.

    Measured: 3 years

Secondary outcomes (4)

  1. Overall survival (OS)

    Defined as the time from randomization to death from any cause.

    Measured: 5 years

  2. R0 resection rates

    The proportion of patients achieved a complete resection with negative margin.

    Measured: 1 years

  3. Surgical and perioperative treatment safety

    Assessed by evaluation of treatment-related adverse events

    Measured: 1 years

  4. Surgery feasibility

    Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose

    Measured: 30 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2019
  2. Study start10 May 2019
  3. Primary completion1 Apr 2027 (estimated)
  4. Study completion1 Apr 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
The PICC trial is an investigator-initiated, multi-cohort platform trial designed to evaluate the efficacy and safety of neoadjuvant toripalimab, with or without celecoxib, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer. Each cohort within the PICC platform was independently conducted and analyzed according to prespecified objectives.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
270 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03926338
Sponsor's protocol ID
GIHSYSU-14
Acronym
PICC
Status last verified
Nov 2025
First submitted
20 Apr 2019
Last updated
20 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Hu H, Shen X, Li Y, Zhou J, Liu P, Zhang J, Hou Y, Wang X, Deng J, Zheng Z, Li J, Lan P, Wu X, Kang L, Huang M, He Z, He X, Yang Z, Huang L, Wang H, Wang H, Luo S, Chen D, Xie X, Zhang Y, Zhai X, Li S, Li W, Hu J, Yang T, Wang C, Deng W, Huang Y, Cao W, Li F, Shi L, Ling L, Deng Y. Neoadjuvant toripalimab plus celecoxib versus toripalimab monotherapy for mismatch repair-deficient or microsatellite instability-high, locally advanced colorectal cancer (PICC-2): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2026 Aug;27(8):1020-1030. doi: 10.1016/S1470-2045(26)00220-2. Epub 2026 Jul 1.

    PubMed 42385761

  • Cao W, Hu H, Li J, Wu Q, Shi L, Li B, Zhou J, Wang X, Chen J, Wang C, Wang H, Deng W, Huang Y, Deng Y. China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial. Int J Cancer. 2023 Dec 1;153(11):1894-1903. doi: 10.1002/ijc.34647. Epub 2023 Jul 6.

    PubMed 37409565

  • Hu H, Kang L, Zhang J, Wu Z, Wang H, Huang M, Lan P, Wu X, Wang C, Cao W, Hu J, Huang Y, Huang L, Wang H, Shi L, Cai Y, Shen C, Ling J, Xie X, Cai Y, He X, Dou R, Zhou J, Ma T, Zhang X, Luo S, Deng W, Ling L, Liu H, Deng Y. Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):38-48. doi: 10.1016/S2468-1253(21)00348-4. Epub 2021 Oct 22.

    PubMed 34688374

  • Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer. Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.

    PubMed 34606846

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neoadjuvant toripalimab plus celecoxib for 6 cycles, Neoadjuvant toripalimab monotherapy for 6 cycles and Neoadjuvant toripalimab plus celecoxib for 12 cycles in people with Colorectal Cancer and Mismatch Repair-deficient (dMMR), run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yanhong Deng, M.D. (86-13925106525, dengyanh@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response (pCR) rates (PICC-1 and PICC-2 cohorts) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03926338, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.

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