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Single Arm Study of Neoadjuvant Dostarlimab in Stage II and III Deficient Mismatch Repair Colon Cancers (NAIO)

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ClinicalTrials.gov Identifier: NCT05239546
Recruitment Status : Not yet recruiting
First Posted : February 15, 2022
Last Update Posted : February 15, 2022
Information provided by (Responsible Party):
Saima Sharif, University of Iowa

Brief Summary:
This is a Phase II, single arm study looking at the rate of major pathological response in Stage II and III colon cancer after 3 cycles of neoadjuvant Dostarlimab.

Condition or disease Intervention/treatment Phase
Colon Cancer DMMR Colorectal Cancer Drug: Dostarlimab Phase 2

Detailed Description:
This study aims to provide proof of principal that combined neoadjuvant immunotherapy (NAIO) with Dostarlimab alone has significant anti-tumor effect in deficient mismatch repair colon cancer (dMMR CC) with intact primary tumor.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II, Single Arm Study of Neoadjuvant Dostarlimab (TSR-042) in Stage II and III Deficient Mismatch Repair Colon Cancers
Estimated Study Start Date : June 2023
Estimated Primary Completion Date : June 2028
Estimated Study Completion Date : June 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Dostarlimab

Arm Intervention/treatment
Experimental: Neoadjuvant Dostarlimab
Participants will receive Dostarlimab 500 mg IV every 3 weeks for 3 doses pre-operatively
Drug: Dostarlimab
Neoadjuvant Dostarlimab (500mg IV every 3 weeks x 3 doses prior to surgical resection) in patients with Stage II and III dMMR CC.
Other Name: TSR-042

Primary Outcome Measures :
  1. Percentage change in viable tumor cells (VTC) [ Time Frame: After 3 cycles (up to 9 weeks) ]
    To determine rate of Major Pathological Response (MPR) of <10% viable tumor cells (VTC) in Stage II and III Colon resected tumor after 3 cycles of neoadjuvant Dostarlimab, as measured by percent change pre- and post-treatment

Secondary Outcome Measures :
  1. Determine metastatic disease rate (MDR) [ Time Frame: Up to 13 weeks ]
    To determine rate of development of metastatic colon cancer on neoadjuvant Dostarlimab. MDR is defined as the proportion of patients who develop metastatic disease prior to surgery.

  2. Determine disease free survival (DFS) [ Time Frame: Up to 3 years ]
    DFS is defined as the time from treatment initiation to the date of first documentation of disease recurrence or death due to any cause.

  3. Determine overall response rate (ORR) [ Time Frame: Up to 5 years ]
    To estimate ORR on neoadjuvant Dostarlimab. ORR is defined as the proportion of patients with RECIST disease response (CR, PR). All patients that do not meet the criteria for an objective response by the analysis cutoff date will be considered non-responders.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Capable of understanding and complying with the protocol requirements and have signed the informed consent document.
  2. 18 years or older in age
  3. Biopsy proven Stage II or III dMMR (by IHC) Colon Cancer patients amendable to en block surgical resection as determined by colorectal surgeon.
  4. Biopsy specimen should be adequate for CD3+ and CD8+ immunostaining by HalioDx (See lab manual for specimen requirements).
  5. Potentially surgically resectable Stage II or III patients who are willing to try short duration of immunotherapy prior to surgery
  6. ECOG performance status < 1
  7. Absence of metastatic disease on CT CAP with Contrast within 28 days from treatment start
  8. Absolute neutrophil count ≥ 1,500/μL
  9. Platelets ≥ 100,000/μL
  10. Hemoglobin ≥ 9 g/dL
  11. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation
  12. Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
  13. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN
  14. International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy if PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
  15. Participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to taking study treatment and agree to use an adequate method of contraception from screening through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  16. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner starting with first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient

Exclusion Criteria:

  1. Known hypersensitivity to Dostarlimab components or excipients.
  2. Major surgery ≤ 3 weeks prior to initiating protocol therapy
  3. Received investigational therapy ≤ 3 months, or within a time interval less than at least 5 half- lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
  4. History of radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
  5. Heavy bleeding from the colon cancer tumors requiring PRBC transfusions that would require palliative surgical resection
  6. Received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy
  7. Symptomatic, partially obstructing tumors (patients with diverting ostomies are allowed)
  8. Concurrent, clinically significant, active malignancies within two years of study enrollment.
  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  10. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  11. Diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
  12. History of ≥ Grade 3 immune-related AE with prior immunotherapy, except for non-clinically significant lab abnormalities.
  13. Known uncontrolled Human immunodeficiency virus (HIV). Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with documented undetectable viral load and CD 4 count ≥350 within 6 months of the first dose of study treatment are eligible for this trial.
  14. Organ transplant recipients on immunosuppressive medications
  15. Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected).
  16. Prior history of interstitial lung disease.
  17. Received a live vaccine within 14 days of initiating protocol therapy.

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): NCT05239546

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Contact: Saima Sharif, MD 319-356-1616 saima-sharif@uiowa.edu
Contact: Cena Jones-Bitterman 319-353-4596 cena-jones@uiowa.edu

Sponsors and Collaborators
University of Iowa
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Principal Investigator: Saima M Sharif, MD University of Iowa Holden Comprehensive Cancer Center
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Responsible Party: Saima Sharif, Clinical Associate Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT05239546    
Other Study ID Numbers: 202105539
First Posted: February 15, 2022    Key Record Dates
Last Update Posted: February 15, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Saima Sharif, University of Iowa:
Colon cancer
Deficient mismatch repair colon cancer
Additional relevant MeSH terms:
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Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases