Colon Cancer, dMMR Colorectal Cancer
Conditions
Keywords
Colon cancer, dMMR, Deficient mismatch repair colon cancer, MSI-High, MSI-H, Non-operative management, No surgery
Brief summary
This is a Phase II, single arm study looking at the rate of major clinical response and non-operative management in Stage II and III colon cancer after 18 weeks (up to 6 cycles) of neoadjuvant dostarlimab.
Detailed description
The purpose of this research study is to look at the effects of the immunotherapy drug dostarlimab on dMMR colon cancer tumors and to see if these patients can avoid surgical resection, with the option to go to surgery only if the tumor does not respond.
Interventions
DRUGDostarlimab
Participants will receive Dostarlimab 500 mg IV every 3 weeks for 6 cycles followed by 1000 mg every 6 weeks for 8 cycles until 1.5 years
Sponsors
University of Iowa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Capable of understanding and complying with the protocol requirements and have signed the informed consent document. Patients with mild cognitive impairment may be considered for enrollment in the study if their legally authorized representative provides written informed consent for the patient. * 18 years or older in age * Biopsy proven dMMR (by IHC), Stage II or III colon cancer per CT imaging correlation with AJCC 8th edition, 2017, amendable to en block surgical resection as determined by colorectal surgeon. * Biopsy specimen for diagnosis of dMMR Colon cancer should have enough tissue for minimum 4 and max 6 adjacent unstained FFPE slides (4µm each) as determined by Protocol Pathologist Dr. Anthony Snow for CD3+ and CD8+ analysis. If there is not enough tissue present in original sample, a repeat colonoscopy and biopsy may be performed; otherwise patient is not eligible. * Potentially surgically resectable Stage II or III patients who are willing to forgo surgical resection if study endpoints are met. Patient with easily manageable bowel changes amenable to laxatives or stool softeners as outpatient per assessment by colorectal surgery are allowed. (See
Exclusion criteria
#2) * ECOG performance status less than or equal to 1 * Absence of metastatic disease on CT CAP with Contrast within 28 days from treatment start * Absolute neutrophil count greater than or equal to 1,500/µL * Platelets greater than or equal to 100,000/µL * Hemoglobin greater than or equal to 9 g/dL * Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation * Total bilirubin less than or equal to 1.5 x ULN (less than or equal to 2.0 in patients with known Gilberts syndrome) OR direct bilirubin less than or equal to 1 x ULN * Aspartate aminotransferase and alanine aminotransferase less than or equal to 3.0 x ULN * International normalized ratio (INR) or prothrombin time (PT) less than or equal to 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) less than or equal to 1.5× ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants * Participants of childbearing potential must have a negative serum pregnancy test within 72 hours 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Clinical Response (MCR) Rate | From Dostarlimab initiation to 18 weeks. | MCR rate is defined as the proportion of patients meeting the following criteria at 18 weeks: 1) ctDNA is stable or declining, 2) a clinically asymptomatic primary tumor, and 3) no metastatic disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metastasis-Free Survival (MFS) Prior to Surgery | From Dostarlimab initiation until surgery or Dostarlimab completion, up to 2 years. | MFS is defined as the time from treatment initiation to the date of metastasis or death due to any cause, if occurring prior to surgery. Otherwise, patients will be censored at the date of surgery or last radiographic assessment, whichever occurs first. |
| Progression-Free Survival (PFS) | From treatment Dostarlimab until study completion, up to 5 years. | PFS is defined as the time from treatment initiation to the date of first documentation of disease progression (defined as increasing ctDNA, symptomatic primary tumor or metastasis), or death due to any cause. Otherwise, patients will be censored at last radiographic assessment. |
| Overall Response Rate (ORR) | From Dostarlimab initiation until surgery or Dostarlimab completion, up to 2 years. | 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. |
Countries
United States
Contacts
CONTACTSaima Sharif, MD, MS
CONTACTAlisha Demsky
PRINCIPAL_INVESTIGATORSaima M Sharif, MD, MS
University of Iowa Holden Comprehensive Cancer Center
Outcome results
None listed