Rectal Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the safety and clinical activity of combining DCSZ11 with radiation and capecitabine/oxaliplatin (CAPOX) for the neoadjuvant treatment of patients with mismatch repair proficient (pMMR) high risk locally advanced rectal cancer.
Interventions
DRUGDCSZ11
Patients will receive a lead in dose of DCSZ11 (1200 mg administered IV). Three weeks after the lead-in dose, DCSZ11 (1200 mg administered IV) will be administered on Day 1 of each 21 day cycle for a total of 6 cycles of treatment.
RADIATIONRadiation
Patients will receive a short course of radiation (5 Gy for 5 days) two weeks after they receive their lead-in dose of DCSZ11.
DRUGCapecitabine
Patients will receive Capecitabine (1000mg/m\^2 administered by mouth twice a day) will be administered on Days 1 through 14 of each 21 day cycle for a total of 6 cycles of treatment.
DRUGOxaliplatin
Patients will receive Oxaliplatin (130mg/m\^2 administered IV) will be administered on Day 1 of each 21 day cycle for a total of 6 cycles of treatment.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
DynamiCure Biotechnology
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
* Age ≥18 years. * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1. * Rectal cancer (with tumor tissue present at or below the peritoneal reflection) as determined by MRI pelvis or endoscopic ultrasound. * Have histologically proven mismatch repair proficient (pMMR) or microsatellite stable (MSS) rectal adenocarcinoma. * Must not have received any prior systemic treatment or radiation. * Patients have the following clinical staging: * cT4 any node status * Any T stage cN2 node status * Any T or N status, evidence of suspicious lateral lymph nodes \> 10 mm in size in short axis * Evidence of extramural vascular invasion on MRI pelvis * Absence of distant metastases on CT or MRI imaging * Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures. * Left ventricular ejection fraction (LVEF) assessment with documented LVEF ≥ 50% by either TTE or Multigated Acquisition (MUGA) (TTE preferred) within 6 months from first study drug administration. * For both Women and Men, must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug. * Have expected to require any other form of systemic or localized antineoplastic therapy while on study. * Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.). * History of severe hypersensitivity reaction to any monoclonal antibody. * History of encephalitis, meningitis, dementia, Parkinson's or uncontrolled seizures within 1 year prior to the first dose of study drug. * Uncontrolled infection of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or Tuberculosis. * Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements. * Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. * Patient has a pulse oximetry of \<92% on room air. * Patient is on supplemental home oxygen. * Has clinically significant heart disease. * Conditions, including alcohol or drug dependence that would affect the patient's ability to comply with study visits and procedures. * Patient is pregnant or breastfeeding. * Unwilling or unable to follow the study schedule for any reason. * Patient received a live vaccine within 30 days of planned start of study medication. * Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete Response (compCR) Rate | 24 months | compCR is defined as the proportion of subjects with a pathologic complete response at the time of surgical resection or complete clinical response. Pathologic complete response is defined as subjects with no viable tumor cell noted on pathological evaluation of the resection specimen using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0). Complete clinical response is defined as subjects with an absence of tumor on endoscopy and no evidence of metastatic disease or recurrence on imaging for 1 year from the end of treatment. |
| Number of participants experiencing a drug-related toxicity requiring treatment discontinuation | 12 months | Defined using NCI CTCAE v6.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response Rate | 8 months | Pathologic response rate as defined as the proportion of subjects with complete or partial tumor regression at the time of surgery using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0 to 2). |
| Event-Free Survival (EFS) | 24 months | EFS is defined as the number of months from the date of first dose to relapsed disease, development of metastatic disease, or death due to any cause. EFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis. Estimation based on the Kaplan-Meier curve. |
Countries
United States
Contacts
CONTACTColleen Apostal, RN
PRINCIPAL_INVESTIGATOREric Christenson, MD
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medical Institution
Outcome results
None listed