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Active, not recruitingNCT04304209Updated Feb 1, 2023

Pd1 Antibody Sintilimab ± Chemoradiotherapy for Locally Advanced Rectal Cancer

A Phase 2 interventional study of Oxaliplatin and Capecitabine in Colorectal Cancer Stage II and Colorectal Cancer Stage III, sponsored by Sun Yat-sen University. Active, not recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-02-01.

Sponsored by Sun Yat-sen University · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Registered 4 months after the study started (first participant enrolled Oct 2019, registered Mar 2020).
Phase
Phase 2
Study type
Interventional
Enrollment
195
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

In this study, participants with locally advanced rectal cancer patients will be treated according to MMR/MSI status. There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, dMMR or MSI-H patients will receive 4 cycles of neoadjuvant Pd1 antibody Sintilimab,followed by one of the following treatments: (1) surgery and adjuvant treatment, (2）another 4 cycles of sintilimab, followed by radical surgery or observation (only for cCR) . For Cohort B, pMMR/MSS/MSI-L patients will be randomized to receive neoadjuvant chemoradiotherapy ± four cycles of Pd1 antibody Sintilimab，followed by one of the following treatments: (1) curative surgery and four cycles of adjuvant chemotherapy;(2)four cycles of chemotherapy then observation (only cCR after neoadjuvant therapy)

02

Conditions studied

  • Colorectal Cancer Stage II
  • Colorectal Cancer Stage III
03

In context

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's planned enrollment of 195 is above the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Browse Colorectal Neoplasms studies →

Lead sponsor

Sun Yat-sen University is the lead sponsor of 1,644 studies on the registry; 602 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Histologically proven colorectal adenocarcinoma;
  2. Cohort 1: Biopsy tissues with IHC indicates deficient mismatch repair(dMMR),that is,the loss of at least one of the four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSI-H; Cohort 2: Biopsy tissues with IHC indicates proficient mismatch repair(pMMR),that is positivity of all four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSS/MSI-L
  3. Clinical stage for rectal cancer patients is cT3-4N0M0 or cTxN+M0;
  4. Preoperative staging methods: all patients need to accept digital rectal examination(DRE).Patients with rectal cancer undergo high-resolution MRI±ultrasound colonoscopy/transrectal ultrasound for preoperative staging. Perienteric lymph nodes with short diameter ≥10mm or the shape of lymph nodes and its MRI characteristics are consistent with typical lymph node metastasis. If endoscopic ultrasonography is used in combination, and there is a contradiction between staging methods, the data should be submitted to the evaluation team of our center for the accurate staging;
  5. No symptoms of ileus; or ileus is alleviated after proximal colostomy.
  6. No rectal surgery except preventative stoma;
  7. No chemotherapy or radiotherapy;
  8. No biotherapy (e.g.monoclonal antibodies), immunotherapy (e.g.anti-PD-1 antibody,anti-PD-L1 antibody,anti-PD-L2 antibody or CTLA-4 antibody),or other clinical trials agents;
  9. No limit to previous endocrine therapy.
  10. Age between 18 and 75 years;
  11. ECOG performance status of 0 or 1;
  12. Life expectancy: more than 2 years;
  13. Hematopoietic: WBC>3×109/L;PLT>80×109/L; Hb>90g/L;
  14. Hepatic: ALT and AST\<2 times upper limit of normal (ULN); bilirubin\<1.5 times ULN;
  15. Renal: creatinine \<1.5 times ULN or creatinine clearance ≥ 60 mL/min.

Exclusion criteria

Exclusion Criteria:

  1. Arrhythmias require antiarrhythmic therapy (with the exception of β-blockers or digoxin), symptomatic coronary artery disease or local myocardial ischemia (myocardial infarction within the past 6 months) or congestive heart failure exceeding NYHA II;
  2. Severe hypertension with poor control after medication;
  3. A known history of testing positive for HIV or chronic hepatitis B or C (high copy virus DNA) at active stage;
  4. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;
  5. Other active severe clinical infections (NCI-CTC5.0);
  6. Apparent distant metastasis away from the pelvic before surgery;
  7. Cachexia, organ function decompensation;
  8. Previous pelvic or abdominal radiotherapy;
  9. Multiple primary colorectal cancers;
  10. Epilepsy require medical treatment (such as steroid or antiepileptic therapy);
  11. Other malignancy within the past 5 years with the exception of effectively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;
  12. Drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study;
  13. Patients have any active autoimmune diseases or a history of autoimmune diseases(including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included.
  14. Received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;
  15. Complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(>10mg/day prednisone or other therapeutic hormones);
  16. Known or suspected allergy to the study drugs or to any drugs related to this trial;
  17. Any unstable condition or which endangers the patients' safety and compliance;
  18. Pregnant or breast-feeding women who are fertile without effective contraception;
  19. Refuse to sign the informed consent.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
195 participants (estimated)

Study arms

  • Experimental
    Cohort A

    After 4 cycles of neoadjuvant sintilimab treatment, the patients and doctors could choose one of the following treatments: (1) surgery, followed by 4 cycles of adjuvant sintilimab with or without Capeox chemotherapy; (2) another 4 cycles of sintilimab, followed by radical surgery or observation (only for patients with clinical complete response).

    Drug: Oxaliplatin · Drug: Capecitabine · Drug: Sintilimab · Procedure: total mesorectal excision · Other: Watch and wait

  • Experimental
    Cohort B-arm 1

    After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)

    Drug: Oxaliplatin · Drug: Capecitabine · Drug: Sintilimab · Radiation: radiotherapy · Procedure: total mesorectal excision · Other: Watch and wait

  • Active comparator
    Cohort B-arm 2

    After four cycles of neoadjuvant Capeox chemotherapy and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)

    Drug: Oxaliplatin · Drug: Capecitabine · Radiation: radiotherapy · Procedure: total mesorectal excision · Other: Watch and wait

Interventions

  • DrugOxaliplatin

    130mg/m2, d1 q3w, in Capeox regimen (100mg/m2 when used cocurrently with radiotherapy), intravenous infusion

  • DrugCapecitabine

    1000mg/m2, bid, qd1-14, q3w, in Capeox regimen, oral administration

  • DrugSintilimab

    200mg, d1 q3w, intravenous infusion

  • Radiationradiotherapy

    neoadjuvant radiotherapy with 50Gy to GTV, 45Gy to CTV in 25 fractions.

  • Proceduretotal mesorectal excision

    total mesorectal excision after neoadjuvant treatment

  • OtherWatch and wait

    Watch and wait for cCR patients after neoadjuvant treatment

06

What researchers measure

Primary outcomes

  1. complete response rate

    the proportion of CR cases (pCR for those who underwent surgery and cCR for those who didn't receive surgery)

    Time frame: 6 weeks after curative surgery for pCR; 6 weeks after the completion of neoadjuvant therapy for cCR

Secondary outcomes

  1. Acute toxiticy according CTCAE5.0

    Acute toxiticy according CTCAE5.0

    Time frame: From start of treatment to 3 months after the adjuvant therapy or last dose of treatment

  2. Tumor regresssion grade according to AJCC TRG grading system

    Tumor regresssion grade according to AJCC TRG grading system

    Time frame: 6 weeks after curative surgery

  3. R0 resection rate

    R0 resection rate

    Time frame: 6 weeks after curative surgery

  4. Local recurrence

    Local recurrence

    Time frame: 5 years after curative surgery

  5. Distant metastasis

    Distant metastasis

    Time frame: 5 years after curative surgery

  6. Tumor response

    tumor volume reduction rate (TVRR) reaching 20% or above

    Time frame: 6 weeks after first study treatment

07

Study locations

1 site
  • Medical Oncology,Sun Yat-sen University Cancer Center
    Guangzhou, Guangdong 510060, China
08

References and documents

Publications

  • Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial. J Natl Cancer Inst. 2015 Sep 14;107(11):djv248. doi: 10.1093/jnci/djv248. Print 2015 Nov. Erratum In: J Natl Cancer Inst. 2016 Mar 08;108(4):djw057. doi: 10.1093/jnci/djw057. J Natl Cancer Inst. 2018 Jul 1;110(7):794. doi: 10.1093/jnci/djy096. PubMed 26374429 ↗
  • Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30. PubMed 26028255 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 1, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04304209
Lead sponsor
Sun Yat-sen University
Responsible party
Ruihua Xu (Professor, Sun Yat-sen University) — Principal investigator
First posted
Mar 11, 2020
Start date
Oct 28, 2019
Primary completion
Oct 18, 2026 (estimated)
Completion
Oct 18, 2026 (estimated)
Last update
Feb 1, 2023

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jan 2023. You cannot join it, but the record below documents what was studied.

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