NAIO: Single Arm Study of Neoadjuvant Dostarlimab in Stage II and III Deficient Mismatch Repair Colon Cancers
Study Details
Study Description
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 |
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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 Names:
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Outcome Measures
Primary Outcome Measures
- Percentage change in viable tumor cells (VTC) [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
- Determine metastatic disease rate (MDR) [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.
- Determine disease free survival (DFS) [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.
- Determine overall response rate (ORR) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Capable of understanding and complying with the protocol requirements and have signed the informed consent document.
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18 years or older in age
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Biopsy proven Stage II or III dMMR (by IHC) Colon Cancer patients amendable to en block surgical resection as determined by colorectal surgeon.
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Biopsy specimen should be adequate for CD3+ and CD8+ immunostaining by HalioDx (See lab manual for specimen requirements).
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Potentially surgically resectable Stage II or III patients who are willing to try short duration of immunotherapy prior to surgery
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ECOG performance status < 1
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Absence of metastatic disease on CT CAP with Contrast within 28 days from treatment start
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Absolute neutrophil count ≥ 1,500/μL
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Platelets ≥ 100,000/μL
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Hemoglobin ≥ 9 g/dL
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Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation
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Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
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Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN
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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
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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.
- 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:
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Known hypersensitivity to Dostarlimab components or excipients.
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Major surgery ≤ 3 weeks prior to initiating protocol therapy
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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.
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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.
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Heavy bleeding from the colon cancer tumors requiring PRBC transfusions that would require palliative surgical resection
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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
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Symptomatic, partially obstructing tumors (patients with diverting ostomies are allowed)
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Concurrent, clinically significant, active malignancies within two years of study enrollment.
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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.
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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.
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Diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
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History of ≥ Grade 3 immune-related AE with prior immunotherapy, except for non-clinically significant lab abnormalities.
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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.
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Organ transplant recipients on immunosuppressive medications
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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).
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Prior history of interstitial lung disease.
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Received a live vaccine within 14 days of initiating protocol therapy.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Iowa
Investigators
- Principal Investigator: Saima M Sharif, MD, University of Iowa Holden Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 202105539