Combining DCSZ11 With Radiation and Chemotherapy as Neoadjuvant Treatment for pMMR Locally Advanced Rectal Cancer

Official title

Combining CD93 Inhibition (DCSZ11) With Short Course Radiation and Chemotherapy as Part of Total Neoadjuvant Treatment (TNT) for High-risk Mismatch Repair Proficient (pMMR) Locally Advanced Rectal Cancer (LARC)

Overview

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

• Drug DCSZ11
  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.
• Radiation Radiation
  Patients will receive a short course of radiation (5 Gy for 5 days) two weeks after they receive their lead-in dose of DCSZ11.
• Drug Capecitabine
  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.
• Drug Oxaliplatin
  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.

Primary outcome measures

• Composite Complete Response (compCR) Rate [Time frame: 24 months]
• Number of participants experiencing a drug-related toxicity requiring treatment discontinuation [Time frame: 12 months]

Secondary outcome measures (2)

• Pathologic Response Rate [Time frame: 8 months]
• Event-Free Survival (EFS) [Time frame: 24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Johns Hopkins SKCCC — Baltimore

Identifiers

NCT: NCT07580339 · J2652 · IRB00536619

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗