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DMMR Colorectal CancerPhase 2NCT04301557

PD1 Antibody Toripalimab and Chemoradiotherapy for dMMR/MSI-H Locally Advanced Colorectal Cancer

A Phase 2 study testing PD-1 Antibody, Oxaliplatin and Capecitabine in people with DMMR Colorectal Cancer and MSI-H Colorectal Cancer, 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 The sponsor has not verified this record for over two years, so it may be out of date.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

PD1 antibody is now recommended for dMMR/MSI-H metastatic colorectal cancer patients as second line. Chemoradiotherapy is standand treatment for locally advanced rectal cancer and is also recommended as an alternative choice for unresectable locally advanced colon cancer. Read more about this study

Who is it for?
Ages 18 to 72 years
What is being tested?
PD-1 Antibody, Oxaliplatin and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteChina
Study dates
31 Jul 2020to 30 Dec 2024
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 72 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven diagnosis of colorectal adenocarcinoma;
  • 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;
  • Clinical stage for rectal cancer patients is cT3-4N0M0 or cTxN+M0;clinical stage of colon cancer should meet the following criteria (any one is sufficient): a)Tumor penetrates the whole wall and adherents to other organs or structures around(T4b).Tumor cannot reach R0 resection by imaging assessment; b)The intestinal lymph nodes involved are closely adjacent to large abdominal vessels. Lymph nodes dissection is not feasible by imaging assessment; c)Surgeons assess it is hard to achieve R0 resection after surgical exploration; d)Surgeons assess tumor is extensive multiviseral resection is needed, which is expected to damage the organs and seriously affect the quality of life after operation;
  • 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.
  • Previous treatment:
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  • No surgery except preventative stoma;
  • 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.
  • Patient characteristics:
  • Age between 18 and 72 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

  • All patients enrolled cannot have any of the following situation:
  • 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 drug control;
  • 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);
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  • Apparent distant metastasis away from the pelvic before surgery;
  • 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.
  • Exit Criteria:
  • Patients withdraw the informed consent and ask for quit;
  • Poor compliance;
  • Disease progression during treatment;
  • Serious adverse events or serious adverse reactions (SAE) occurred during the study;
  • Any delay of treatment for more than two weeks (including two weeks) (referring to the delay of all drugs in the medication plan) shall be discussed by the researchers whether to quit.
  • Cessation Criteria:
  • Study suspension refers to the cessation of the whole study before the end of the program. The main purpose of this action is to protect the rights and interests of the subjects, ensure the quality of the study, and avoid unnecessary economic losses. The whole study will be stopped for the following reasons:
  • Researchers find serious safety issues;
  • Efficacy is poor that there is no need to continue the study;
  • Severe mistakes in the scheme design or important deviations in the implementation process;
  • Funds or management problems;
  • The administrative department decide to cancel the study. A complete suspension of research is either temporary or permanent. When discontinued, all study records shall be retained for future reference.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

PD1 antibody is now recommended for dMMR/MSI-H metastatic colorectal cancer patients as second line. Chemoradiotherapy is standand treatment for locally advanced rectal cancer and is also recommended as an alternative choice for unresectable locally advanced colon cancer. Thus, this study will investigate the efficacy and toxicity of combination strategy using PD1 antibody and chemoradiotherapy for dMMR/MSI-H locally advnaced colorectal cancer patients.

Read the detailed description

PD1 antibody is recommended for dMMR/MSI-H metastatic colorectal cancer patients as second line. Chemoradiotherapy is standand treatment for locally advanced rectal cancer and is also recommended as an alternative choice for unresectable locally advanced colon cancer. Thus, this phase II, single arm study will investigate the efficacy and toxicity of combination strategy using PD1 antibody and chemoradiotherapy for dMMR/MSI-H locally advnaced colorectal cancer patients, which is expected to yield higher tumor regressiona with tolerable toxicity.

Being tested
PD-1 Antibody, Oxaliplatin, Capecitabine, External beam radiotherapy, Total mesorectal excision
Keywords
DMMR Colorectal Cancer, MSI-H Colorectal Cancer, Locally Advanced Colorectal Cancer

What participants receive

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

  • PD-1 AntibodyDrug

    Also called Toripalimab

    PD-1 antibody 240mg,I.V,D1,repeat every 3 weeks, Four cycles in the neoadjuvant treatment, and four cycles in the adjuvant treatment,

  • OxaliplatinDrug

    Oxiliplatin 130mg/m^2 (100mg/m^2 during radiotherapy),I.V,D1,repeat every 3 weeks, Four cycles in the neoadjuvant treatment in Capeox regimen, and two cycles in the adjuvant treatment in Capeox regimen

  • CapecitabineDrug

    Capecitabine 1000mg/m^2,Bid,P.O,D1-D14,repeat every 3 weeks, Four cycles in the neoadjuvant treatment in Capeox regimen, and two cycles in the adjuvant treatment in Capeox regimen, and two cycles in adjuvant treatment in Capecitabine regimen

  • External beam radiotherapyRadiation

    Neoadjuvant radiotherapy, 50Gy/25Fractions to the GTV, 45Gy/25Fractions to the CTV

  • Total mesorectal excisionProcedure or surgery

    Total mesorectal excision

Study groups in NCT04301557
Study groupRoleWhat they receive
PD1 Antibody and Chemoradiotherapy for dMMR/MSI-H LACRCExperimentalInduction regimen: Capeox+PD1 antibody for 1 cycle, Concurrent chemoradiotherapy regimen: Capeox+PD1 antibody for 2 cycles and concurrent , Interval regimen: Capeox+PD1 antibody for 1 cycle, TME surgery or watch and wait for cCR patients Adjuvant regimen: Capeox+PD1 antibody for 2 cycles, Capecitabine+PD1 antibody for 2 cycles
Receives: Drug: PD-1 Antibody; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: External beam radiotherapy; Procedure: Total mesorectal excision

What is being measured

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

  1. Pathological Complete Response(pCR)

    According to pathological response to assess the efficiency of treatment

    Measured: 1 week after surgery

Secondary outcomes (7)

  1. Acute toxicities

    Acute toxicities according to CTCAE5.0

    Measured: Up to 3 months after adjuvant treatment

  2. Tumor regression grade

    Tumor regression grade

    Measured: 1 week after surgery

  3. R0 resection rate

    R0 resection rate

    Measured: 1 week after surgery

  4. Surgical Complication

    Surgical Complication

    Measured: Surgery scheduled 6-8 weeks after the end of neoadjuvant treatment

  5. Local recurrence

    Local recurrence

    Measured: From date of randomization until the date of local recurrence, assessed up to 10 years

  6. Distant metastasis

    Distant metastasis

    Measured: From date of randomization until the date of death of distant metastasis, assessed up to 10 years

  7. 3 year disease free survival

    3 year disease free survival

    Measured: From date of randomization until the date of disease recurrence, assessed up to 3 years

Timeline

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

  1. First posted10 Mar 2020
  2. Study start31 Jul 2020
  3. Primary completion22 Apr 2024 (estimated)
  4. Study completion30 Dec 2024 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04301557
Sponsor's protocol ID
B2019-177-01
Status last verified
Apr 2024
First submitted
23 Feb 2020
Last updated
23 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Corrigendum to "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. 2018 Jul 1;110(7):794. doi: 10.1093/jnci/djy096. No abstract available.

    PubMed 29800481

  • Croner RS, Merkel S, Papadopoulos T, Schellerer V, Hohenberger W, Goehl J. Multivisceral resection for colon carcinoma. Dis Colon Rectum. 2009 Aug;52(8):1381-6. doi: 10.1007/DCR.0b013e3181ab580b.

    PubMed 19617748

  • Lehnert T, Methner M, Pollok A, Schaible A, Hinz U, Herfarth C. Multivisceral resection for locally advanced primary colon and rectal cancer: an analysis of prognostic factors in 201 patients. Ann Surg. 2002 Feb;235(2):217-25. doi: 10.1097/00000658-200202000-00009.

    PubMed 11807361

  • Eldar S, Kemeny MM, Terz JJ. Extended resections for carcinoma of the colon and rectum. Surg Gynecol Obstet. 1985 Oct;161(4):319-22.

    PubMed 4049200

  • Chang H, Yu X, Xiao WW, Wang QX, Zhou WH, Zeng ZF, Ding PR, Li LR, Gao YH. Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study. Onco Targets Ther. 2018 Jan 17;11:409-418. doi: 10.2147/OTT.S150367. eCollection 2018.

    PubMed 29398921

  • Curley SA, Carlson GW, Shumate CR, Wishnow KI, Ames FC. Extended resection for locally advanced colorectal carcinoma. Am J Surg. 1992 Jun;163(6):553-9. doi: 10.1016/0002-9610(92)90554-5.

    PubMed 1595834

  • Xin Yu, WeiWei Xiao, Rong Zhang, LuNing Zhang, Bo Qiu, ZhiFan Zeng, Pei-Rong Ding, Zhi-zhong Pan, Li-ren LI, Yuan-Hong Gao. A pilot study of neoadjuvant chemoradiotherapy for unresectable locally advanced adherent colon cancer: Assessing local tumor response. JCO. 2016; 34（4S）: 727.

  • Qiu B, Ding PR, Cai L, Xiao WW, Zeng ZF, Chen G, Lu ZH, Li LR, Wu XJ, Mirimanoff RO, Pan ZZ, Xu RH, Gao YH. Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer. Chin J Cancer. 2016 Jul 7;35(1):65. doi: 10.1186/s40880-016-0126-y.

    PubMed 27389519

  • Cukier M, Smith AJ, Milot L, Chu W, Chung H, Fenech D, Herschorn S, Ko Y, Rowsell C, Soliman H, Ung YC, Wong CS. Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer: a single institution experience. Eur J Surg Oncol. 2012 Aug;38(8):677-82. doi: 10.1016/j.ejso.2012.05.001. Epub 2012 May 24.

    PubMed 22632848

  • Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829.

    PubMed 16971718

  • Lemery S, Keegan P, Pazdur R. First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the Indication. N Engl J Med. 2017 Oct 12;377(15):1409-1412. doi: 10.1056/NEJMp1709968. No abstract available.

    PubMed 29020592

  • 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

  • Diaz LA Jr, Le DT. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Nov 12;373(20):1979. doi: 10.1056/NEJMc1510353. No abstract available.

    PubMed 26559582

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PD-1 Antibody, Oxaliplatin and Capecitabine in people with DMMR Colorectal Cancer and MSI-H Colorectal Cancer, 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 17 inclusion and 33 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 23 Apr 2024. 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?

Pathological Complete Response(pCR) (time frame: 1 week after surgery). 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 NCT04301557, which also lists 13 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 23 Apr 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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