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Colorectal Cancer Stage IIPhase 2NCT04304209

Pd1 Antibody Sintilimab ± Chemoradiotherapy for Locally Advanced Rectal Cancer

A Phase 2 study testing Oxaliplatin, Capecitabine and Sintilimab in people with Colorectal Cancer Stage II and Colorectal Cancer Stage III, run by Sun Yat-sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Oxaliplatin, Capecitabine and Sintilimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
195 participants
Where
1 siteChina
Study dates
28 Oct 2019to 18 Oct 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Histologically proven colorectal adenocarcinoma;
  • 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
  • Clinical stage for rectal cancer patients is cT3-4N0M0 or cTxN+M0;
  • 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;
  • No symptoms of ileus; or ileus is alleviated after proximal colostomy.
  • No rectal surgery except preventative stoma;
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  • No chemotherapy or radiotherapy;
  • 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;
  • No limit to previous endocrine therapy.
  • Age between 18 and 75 years;
  • ECOG performance status of 0 or 1;
  • Life expectancy: more than 2 years;
  • Hematopoietic: WBC>3×109/L;PLT>80×109/L; Hb>90g/L;
  • Hepatic: ALT and AST<2 times upper limit of normal (ULN); bilirubin<1.5 times ULN;
  • Renal: creatinine <1.5 times ULN or creatinine clearance ≥ 60 mL/min.

Who cannot join

  • 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;
  • Severe hypertension with poor control after medication;
  • A known history of testing positive for HIV or chronic hepatitis B or C (high copy virus DNA) at active stage;
  • Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;
  • Other active severe clinical infections (NCI-CTC5.0);
  • Apparent distant metastasis away from the pelvic before surgery;
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  • Cachexia, organ function decompensation;
  • Previous pelvic or abdominal radiotherapy;
  • Multiple primary colorectal cancers;
  • Epilepsy require medical treatment (such as steroid or antiepileptic therapy);
  • 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;
  • Drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study;
  • 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.
  • Received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;
  • Complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(>10mg/day prednisone or other therapeutic hormones);
  • Known or suspected allergy to the study drugs or to any drugs related to this trial;
  • Any unstable condition or which endangers the patients' safety and compliance;
  • Pregnant or breast-feeding women who are fertile without effective contraception;
  • Refuse to sign the informed consent.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Medical Oncology,Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

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)

Being tested
Oxaliplatin, Capecitabine, Sintilimab, radiotherapy, total mesorectal excision
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • OxaliplatinDrug

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

  • CapecitabineDrug

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

  • SintilimabDrug

    200mg, d1 q3w, intravenous infusion

  • radiotherapyRadiation

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

  • total mesorectal excisionProcedure or surgery

    total mesorectal excision after neoadjuvant treatment

  • Watch and waitOther

    Watch and wait for cCR patients after neoadjuvant treatment

Study groups in NCT04304209
Study groupRoleWhat they receive
Cohort AExperimentalAfter 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).
Receives: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Sintilimab; Procedure: total mesorectal excision; Other: Watch and wait
Cohort B-arm 1ExperimentalAfter 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)
Receives: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Sintilimab; Radiation: radiotherapy; Procedure: total mesorectal excision; Other: Watch and wait
Cohort B-arm 2Active comparatorAfter 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)
Receives: Drug: Oxaliplatin; Drug: Capecitabine; Radiation: radiotherapy; Procedure: total mesorectal excision; Other: Watch and wait

What is being measured

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

  1. complete response rate

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

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

Secondary outcomes (6)

  1. Acute toxiticy according CTCAE5.0

    Acute toxiticy according CTCAE5.0

    Measured: 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

    Measured: 6 weeks after curative surgery

  3. R0 resection rate

    R0 resection rate

    Measured: 6 weeks after curative surgery

  4. Local recurrence

    Local recurrence

    Measured: 5 years after curative surgery

  5. Distant metastasis

    Distant metastasis

    Measured: 5 years after curative surgery

  6. Tumor response

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

    Measured: 6 weeks after first study treatment

Timeline

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

  1. First posted11 Mar 2020
  2. Study start28 Oct 2019
  3. Primary completion18 Oct 2026 (estimated)
  4. Study completion18 Oct 2026 (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
Parallel groups
Masking
None (open label)
Enrolment
195 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04304209
Sponsor's protocol ID
B2019-149
Status last verified
Jan 2023
First submitted
9 Mar 2020
Last updated
1 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

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.

    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

  • Chen G, Jin Y, Guan WL, Zhang RX, Xiao WW, Cai PQ, Liu M, Lin JZ, Wang FL, Li C, Quan TT, Xi SY, Zhang HZ, Pan ZZ, Wang F, Xu RH. Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: an open-label, single-centre phase 2 study. Lancet Gastroenterol Hepatol. 2023 May;8(5):422-431. doi: 10.1016/S2468-1253(22)00439-3. Epub 2023 Mar 1.

    PubMed 36870360

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oxaliplatin, Capecitabine and Sintilimab in people with Colorectal Cancer Stage II and Colorectal Cancer Stage III, 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 15 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 1 Feb 2023. 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?

Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

complete response rate (time frame: 6 weeks after curative surgery for pCR; 6 weeks after the completion of neoadjuvant therapy for cCR). 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 NCT04304209, which also lists 3 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 1 Feb 2023.

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Clinical Trial NCT04304209 | AzTrials