Clinical Trials /

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

NCT04301557

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PD1 Antibody Toripalimab and Chemoradiotherapy for dMMR/MSI-H Locally Advanced Colorectal Cancer
  • Official Title: PD1 Antibody Toripalimab and Chemoradiotherapy for dMMR/MSI-H Locally Advanced Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: B2019-177-01
  • NCT ID: NCT04301557

Conditions

  • DMMR Colorectal Cancer
  • MSI-H Colorectal Cancer
  • Locally Advanced Colorectal Cancer

Interventions

DrugSynonymsArms
PD-1 AntibodyToripalimabPD1 Antibody and Chemoradiotherapy for dMMR/MSI-H LACRC
OxaliplatinPD1 Antibody and Chemoradiotherapy for dMMR/MSI-H LACRC
CapecitabinePD1 Antibody and Chemoradiotherapy for dMMR/MSI-H LACRC

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
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
  • PD-1 Antibody
  • Oxaliplatin
  • Capecitabine

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically proven diagnosis of colorectal adenocarcinoma;

          2. 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;

          3. 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;

          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.

        Previous treatment:

          1. No surgery except preventative stoma;

          2. No chemotherapy or radiotherapy;

          3. 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;

          4. No limit to previous endocrine therapy.

        Patient characteristics:

          1. Age between 18 and 72 years;

          2. ECOG performance status of 0 or 1;

          3. Life expectancy: more than 2 years;

          4. Hematopoietic: WBC>3×109/L;PLT>80×109/L; Hb>90g/L;

          5. Hepatic: ALT and AST<2 times upper limit of normal (ULN); bilirubin<1.5 times ULN;

          6. Renal: creatinine <1.5 times ULN or creatinine clearance ≥ 60 mL/min.

        Exclusion Criteria:

        All patients enrolled cannot have any of the following situation:

          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 drug control;

          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.

        Exit Criteria:

          1. Patients withdraw the informed consent and ask for quit;

          2. Poor compliance;

          3. Disease progression during treatment;

          4. Serious adverse events or serious adverse reactions (SAE) occurred during the study;

          5. 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:

          1. Researchers find serious safety issues;

          2. Efficacy is poor that there is no need to continue the study;

          3. Severe mistakes in the scheme design or important deviations in the implementation
             process;

          4. Funds or management problems;

          5. 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.
      
Maximum Eligible Age:72 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological Complete Response(pCR)
Time Frame:1 week after surgery
Safety Issue:
Description:According to pathological response to assess the efficiency of treatment

Secondary Outcome Measures

Measure:Acute toxicities
Time Frame:Up to 3 months after adjuvant treatment
Safety Issue:
Description:Acute toxicities according to CTCAE5.0
Measure:Tumor regression grade
Time Frame:1 week after surgery
Safety Issue:
Description:Tumor regression grade
Measure:R0 resection rate
Time Frame:1 week after surgery
Safety Issue:
Description:R0 resection rate
Measure:Surgical Complication
Time Frame:Surgery scheduled 6-8 weeks after the end of neoadjuvant treatment
Safety Issue:
Description:Surgical Complication
Measure:Local recurrence
Time Frame:From date of randomization until the date of local recurrence, assessed up to 10 years
Safety Issue:
Description:Local recurrence
Measure:Distant metastasis
Time Frame:From date of randomization until the date of death of distant metastasis, assessed up to 10 years
Safety Issue:
Description:Distant metastasis
Measure:3 year disease free survival
Time Frame:From date of randomization until the date of disease recurrence, assessed up to 3 years
Safety Issue:
Description:3 year disease free survival

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sun Yat-sen University

Trial Keywords

  • DMMR Colorectal Cancer
  • MSI-H Colorectal Cancer
  • Locally Advanced Colorectal Cancer

Last Updated

March 9, 2020