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Watch and Wait in PD-1 Monoclonal Antibody Treated dMMR/MSI-H Distal Rectal Cancer (BASKET)

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ClinicalTrials.gov Identifier: NCT04643041
Recruitment Status : Recruiting
First Posted : November 24, 2020
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
Sixth Affiliated Hospital, Sun Yat-sen University

Brief Summary:
Immunotherapy has achieved significant therapeutic effect in DNA mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) , more than fifty percent of dMMR/MSI-H CRC patients might get pathological complete response(pCR) after PD-1 monoclonal antibody treatment. For distant rectal cancer(RC), radical resection and neoadjuvant chemotherapy or chemoradiotherapy might cause lots of treatment cost,damage to defecation and sexual function, acute toxicity, chronic dysfunction, even loss of anus and psychological disorder. This study aims to evaluate the effect and safety of watch and wait in patients with dMMR/MSI-H distal RC accessed pCR after PD-1 monoclonal antibody therapy.

Condition or disease Intervention/treatment Phase
Rectal Cancer Behavioral: watch and wait Not Applicable

Detailed Description:
Immunotherapy has achieved significant therapeutic effect in DNA mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). MMR expression and MSS status are the important effective factors of immunotherapy. PD-1monocolnal antibody therapy has accessed excellent treatment effect in advanced dMMR/MSI-H CRC and neoadjuvant therapeutic effect in early colon cancer, more than fifty percent of dMMR/MSI-H CRC patients might get pathological complete response(pCR) after PD-1 monoclonal antibody treatment. The treatments had been proved to be safe and the toxicities were controllable. Rectal cancer(RC) is one of the most common malignant tumors in China. So far, radical resection with or without neoadjuvant chemotherapy of chemoradiotherapy are still standard comprehensive treatments recommended to distal RC by NCCN, ESMO and CSCO. For distant RC, radical resection and neoadjuvant chemotherapy or chemoradiotherapy might cause lots of treatment cost,damage to defecation and sexual function, acute toxicity, chronic dysfunction, even loss of anus and psychological disorder. So far, whether watch and wait could be performed in patients with dMMR/MSI-H distal RC accessed pCR after PD-1 monoclonal antibody therapy or not is still not clear. Thus, this study aims to evaluate the effect and safety of watch and wait in patients with dMMR/MSI-H distal RC accessed pCR after PD-1 monoclonal antibody therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: patients with DNA mismatch repair-deficient or microsatellite instability-high distal rectal cancer
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Watch and Wait in Patients With dMMR/MSI-H Distal Rectal Cancer Accessed Pathological Complete Response After PD-1 Monoclonal Antibody Therapy-an Open Label, Multicenter, Prospective Study (BASKET)
Actual Study Start Date : January 1, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: watch and wait
patients with DNA mismatch repair-deficient or microsatellite instability-high distal rectal cancer accessed pathological complete response after 6 courses of PD-1 monoclonal antibody (200mg/Course/Q3W) therapy and start watch and wait.
Behavioral: watch and wait
patients with DNA mismatch repair-deficient or microsatellite instability-high distal rectal cancer accessed pathological complete response after 6 courses of PD-1 monoclonal antibody (200mg/Course/Q3w) therapy and start watch and wait.




Primary Outcome Measures :
  1. 1 year DFS rate [ Time Frame: 1 year ]
    1 year Disease Free Survival Rate


Secondary Outcome Measures :
  1. Incidence rate of Grade ≥3 PD-1monoclonal antibody-related adverse events [ Time Frame: 1 year ]
    Incidence rate of participants with Grade ≥3 PD-1monoclonal antibody-related adverse events as assessed by CTCAE v4.0

  2. local recurrent rate [ Time Frame: 3 years ]
    local recurrent rate of original rectal cancer

  3. distant metastasis rate [ Time Frame: 3 years ]
    distant metastasis rate

  4. 3 years DFS Rate [ Time Frame: 3 years ]
    3 years Disease Free Survival Rate

  5. 3 years OS rate [ Time Frame: 3 years ]
    3 years Overall Survival Rate



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Preliminary inclusion criteria:

  • Histological identified rectal adenocarcinoma,
  • Tumor biopsy immunohistochemical (IHC) identified dMMR, including one or more deficient of the MSH1,MSH2,MSH6 and PMS2 protein expression and diagnosed as deficient mismatch repair(dMMR), or next generation sequencing identified (MSI-H); MRI identified tumor inferior margin lower than peritoneal reflection,
  • Clinical staging TxNxM0, with or without positive MRF, with or without positive EMVI,
  • Staging method:all patients undergo rectal palpation, high resolution MRI ± transrectal Ultrasound examination,positive perienteric lymph node(LN): short diameter ≥10mm LN or LN with typical metastatic shape and MRI character, clinical data should be re-evaluated and judged by center evaluation group when there are contradictory stagings,distant metastasis were excluded by chest and abdominal enhanced CT and pelvic enhanced MRI,
  • No intestinal obstruction symptom,or obstruction relieved after proximal colostomy,
  • No rectal surgery history,
  • No chemotherapy or radiotherapy history,
  • No biopharmaceutical treatment history(such as monoclonal antibody), immunotherapy(such as anti PD-1antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4), or other research drug treatment,
  • Endocrinotherapy history restriction:No
  • Informed consent assigned, Final inclusion criteria:
  • Clinical complete response (cCR)(Chest,abdominal and pelvic enhanced CT or pelvic enhanced MRI or transrectal ultrasound proved)
  • Transrectal ultrasound biopsy or endoscopic biopsy proved pathologically complete response (pCR)

Exclusion Criteria:

  • Arrhythmia need anti-arrhythmia treatment(except β-blocking agent or Digoxin),symptomatic coronary heart disease or myocardial ischemia(myocardial infarction within 6 months) or congestive heart-failure (CHF) > NYHA grade II,
  • Severe hypertension not well controlled by drugs,
  • HIV infection history or active phase of chronic Hepatitis B or C(high copies of virus DNA),
  • Active tuberculosis(TB),accepting anti-TB treatment or anti-TB treatment within 1 year before trial screen,
  • Other active clinical severe infection(NCI-CTC V5.0),
  • Outside pelvic distant metastasis evidences,
  • Dyscrasia, organ dysfunction,
  • Pelvic or abdominal radiotherapy history,
  • Multiple CRC or Multi-primary tumors;
  • Epilepsy need treatments(Steroid or anti-epilepsy therapy),
  • Other malignant tumor history within 5 years,
  • Over abuse of drugs, medical and psychological or social conditions that might interfere patients or evaluation of the study results,
  • Any active autoimmune disease or autoimmune disease history (including but not restricted:interstitial pneumonia, uveitis,enteritis, hepatitis,hypophysitis, nephritis, hyperthyroidism, hypothyroidism, asthma need bronchodilators),
  • Any anti-infection vaccine injection 4 weeks before inclusion ,
  • Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose>10mg/day prednisolone or equivalent hormone);
  • Known or suspicious allergy to any study related drugs,
  • Any unstable state might cause damage to the safety and compliance of patients,
  • Pregnant or breast feeding women who has ability to have children while without contraception,
  • Refuse to sign informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04643041


Contacts
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Contact: Jun Huang, MD +8613926451242 huangj97@mail.sysu.edu.cn
Contact: Jianping Wang, MD +8613808874808 wangjpgz@126.com

Locations
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China, Guangdong
Sun Yatsen University Recruiting
Guangzhou, Guangdong, China
Contact: Jun Huang, MD    +8613926451242    huangj97@mail.sysu.edu.cn   
Sponsors and Collaborators
Sixth Affiliated Hospital, Sun Yat-sen University
Investigators
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Study Chair: Jianping Wang, MD Sixth Affiliated Hospital, Sun Yat-sen University
Study Chair: Jun Huang, MD Sixth Affiliated Hospital, Sun Yat-sen University
Publications:
Scott E. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Department of Medicine; Department of Biostatistics and Computational Biology; Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Johns Hopkins University, Baltimore; University of Wisconsin Carbone Cancer Center; School of Medicine and Public Health; Madison; Fox Chase Cancer Center, Temple University Health System, Philadelphia; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis; Mayo Clinic, Rochester, MN; University Hospitals Case Medical Center, Seidman Cancer Center; Cleveland Clinic Taussig Cancer Institute; Both in Cleveland; University of Virginia Cancer Center, Charlottesville; Comprehensive Cancer Centers of Nevada, Las Vegas; Siteman Cancer Center, Washington University School of Medicine, St. Louis; NorthShore University Health System, Evanston, IL; University of Michigan Comprehensive Cancer Center, Ann Arbor; Rutgers Cancer Institute of New Jersey, New Brunswick.N Engl J Med. 2015 Aug 20;373(8):737-46. [Epub 2015 Aug 5]. doi: 10.1056/NEJMoa1503747. Urol Oncol. 2017 Mar;35(3):123. doi: 10.1016/j.urolonc.2016.12.021. Epub 2017 Feb 1.

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Responsible Party: Sixth Affiliated Hospital, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04643041    
Other Study ID Numbers: E2020132
First Posted: November 24, 2020    Key Record Dates
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sixth Affiliated Hospital, Sun Yat-sen University:
PD-1 monoclonal antibody
watch and wait
dMMR/MSI-H
distal rectal cancer
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases