Perioperative MVT-5873, a Fully Human Monoclonal Antibody Against a CA 19-9 Epitope, for Operable CA 19-9 Producing Pancreatic Cancers, Cholangiocarcinomas, and Metastatic Colorectal Cancers

Brief summary public domain (ClinicalTrials.gov)

Background: Gastrointestinal tumors have a molecule called carbohydrate antigen 19-9 (CA19-9) in the tumors and blood. The agent MVT-5873 was designed to block this molecule. Researchers want to test how safe it is to give this agent to people before and after surgery to remove a tumor. They want to learn the highest dose tolerated. They want to see if getting the agent at surgery helps slow down the disease. Objective: To test the safety of giving MVT-5873 at surgery to remove cancer and see if it slows the progression of the disease. Eligibility: Adults at least 18 years old with certain cancers and certain blood CA19-9 levels Design: Participants will be screened with: * Medical history * Physical exam * Blood and heart tests * Scans * Review of normal activities * Review of tumor sample * Pregnancy test A few days before surgery, participants will get a dose of the study agent. They will get it through a small plastic tube in a vein over about 2 hours. Participants will sign a separate consent and have the surgery. A sample of the tumor and normal liver will be removed for research. For 1-2 weeks after surgery, participants will recover in intensive care then regular care at the hospital. They will be monitored and treated throughout the stay. After leaving the hospital, participants will get the study agent every week for 1 month. Then they will get it every other week for 2 months. They will repeat screening tests at study visits and at a follow-up visit. That will be about 5 weeks after the last dose.

Detailed description public domain (ClinicalTrials.gov)

Background: * Resections to remove tumors in the liver, bile ducts and pancreas are rarely curative, and patients frequently succumb to disease recurrence in the ensuing months to year(s) after the operation. * Standard adjuvant therapies, which typically begin 6-12 weeks after surgery, offer little demonstrable decreases in the rates of tumor recurrence. * The concept and implementation of immediate perioperative therapy has not been evaluated given the serious concerns related to healing and recovery with standard cytotoxic chemotherapy and newer targeted agents. * A significant percentage of metastatic colorectal cancers, and primary tumors of the pancreas and bile ducts express Sialyl Lewis, an epitope on the well-established tumor marker, Carbohydrate antigen 19-9 (CA19-9). * MVT-5873, a fully human antibody against Sialyl Lewis, has displayed antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro, potentiated chemotherapeutic efficacy in mouse models and demonstrated efficacy in Phase 1 trials of patients with advanced inoperable Hepato-pancreato-biliary (HPB) cancers. * MVT-5873 is well tolerated as a single agent; moderate elevations in aspartate aminotransferase (AST)/alanine aminotransferase (ALT) appear to be dose-limiting. * Patients with resectable Sialyl Lewis-expressing cancers represent an ideal population to explore the use of perioperative MVT-5873 given moderate level of CA 19-9 elevations, and the potential for extension of recurrence-free survival. Objectives: * Document the safety of perioperative MVT-5873 in patients undergoing pancreas and liver resections. * Determine if perioperative MVT-5873 can decrease 1-year recurrence rates for patients with operable CA 19-9-producing cancers. Eligibility: * Histologically or cytologically confirmed adenocarcinoma of the * Colon (metastatic to liver) * Pancreas * Bile Ducts (Cholangiocarcinoma) * Serum CA19-9 levels greater than the upper limit of normal, but less than 2500. * Disease amenable to complete surgical extirpation. Design: -Pre-operative one-time treatment with MVT-5873, resection to remove all demonstrable disease in the liver, bile ducts and pancreas, and continuing MVT-5873 mono-therapy until off treatment criteria are met.

Intervention public domain (ClinicalTrials.gov)

Drug: MVT-5873. 1 mg/kg or 3 mg/kg for pre-operative dose, 1 mg/kg during post-operative period

Intervention public domain (ClinicalTrials.gov)

Procedure: pancreatectomy or hepatectomy. Pancreatectomy or hepatectomy

Arm public domain (ClinicalTrials.gov)

Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (experimental): Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment

Arm public domain (ClinicalTrials.gov)

Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (experimental): Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment

Primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Disease Recurrence At 1 Year. Disease recurrence is defined as new disease measurable on computed tomography (CT)/magnetic resonance imaging (MRI) that was not present on the baseline CT/MRI. Time frame: 1 year.

Primary outcome public domain (ClinicalTrials.gov)

Number of Grade 3-5 Adverse Events Related and/or Not Related to Drug. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events. Time frame: Date treatment consent signed to date off study, approximately 29 months and 11 days, and 22 months and 21 days for cohort 1 and cohort 2 respectively..

Secondary outcome public domain (ClinicalTrials.gov)

Define Disease Free Survival (DFS) for Participants Treated With Preoperative MVT-5873. Time frame: An average of 15.17 months.

Eligibility public domain (ClinicalTrials.gov)

* INCLUSION CRITERIA: * Subjects must have histologically or cytologically confirmed diagnoses of adenocarcinoma in one of the following scenarios: * Primary tumors of the pancreas * Primary tumors of the bile duct and ampulla * Metastatic colorectal cancers to the liver * Subjects must have disease resectable with a standard pancreatectomy (pancreaticoduodenectomy or distal pancreatectomy) or liver resection. * Subjects may have received prior therapy, including neoadjuvant regimens. * Subjects must have serum Carbohydrate antigen 19-9 (CA 19-9) elevations greater than the upper limit of normal but less than 2500 U/mL. * Age greater than or equal to 18 years. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 * Subjects must have adequate organ and marrow function as defined below: * leukocytes \>3,000/mcL * absolute neutrophil count \>1,500/mcL * platelets \>90,000/mcL * For subjects with Periampullary cancers that require a pancreaticoduodenectomy for complete tumor extirpation: * total bilirubin \<10 upper limit of normal (ULN)\* * Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) \<5 X institutional upper limit of normal * creatinine \<1.5X institutional upper limit of normal * Subjects with periampullary cancers typically present with biliary obstruction resulting in significant abnormalities in liver function tests that do not reflect liver dysfunction. These values normalize after tumor removal. They can be normalized pre-operatively with biliary stenting, but several large studies have demonstrated an increase in infectious complications with drainage. As such, a practice standard has been to avoid stenting until bilirubin level rises above 10 X ULN. * For subjects with liver tumors (cholangiocarcinoma or metastatic colorectal cancer) requiring a hepatectomy for complete tumor extirpation: * total bilirubin \<2.5 X institutional upper limit of normal\* * AST(SGOT)/ALT(SGPT) \<5 X institutional upper limit of normal\* * creatinine \<1.5X institutional upper limit of normal * Liver abnormalities in this range are consistent with parenchymal destruction from the tumor. * For subjects with pancreas tumors that require a distal pancreatectomy for extirpation: * total bilirubin \<1.5 X institutional upper limit of normal\* * AST(SGOT)/ALT(SGPT) \<2 X institutional upper limit of normal\* * creatinine \<1.5X …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 10 participants (actual).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Disease Recurrence At 1 Year [1 year]. Count Of Participants, Participants. Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 2; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Grade 3-5 Adverse Events Related and/or Not Related to Drug [Date treatment consent signed to date off study, approximately 29 months and 11 days, and 22 months and 21 days for cohort 1 and cohort 2 respectively.]. Number, Adverse events. Grade 3 Abdominal pain - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 2; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Abdominal infection - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 1; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 0. Grade 3 Alanine aminotransferase increased - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 2; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Alkaline phosphatase increased - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 0; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Anemia - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 5; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Aspartate aminotransferase increased - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 3; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Back pain - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 2; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 0. Grade 3 Blood bilirubin increased - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 1; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 0. Grade 3 Confusion - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 0; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Dyspnea - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 0; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Hematuria - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 1; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 0. Grade 3 Hepatobiliary disorders- Other, Bile duct perforation - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 0; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 1. Grade 3 Hyperglycemia - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 2; Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 0. Grade 3 Hypermagnesemia - Not Related: Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=8): 1; Cohort 2 - Pre-oper

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Define Disease Free Survival (DFS) for Participants Treated With Preoperative MVT-5873 [An average of 15.17 months]. Median, months (Full Range). Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1) (n=5): 14.5 (1 to 28); Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1) (n=1): 22 (NA to NA) [Full range cannot be calculated because the participant was taken off study due to study closure.].