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
Condition: Colon Cancer; Pancreatic Cancer; Cholangiocarcinoma; Metastatic Colon Carcinoma; Liver Metastasis
MeSH terms: Pancreatic Neoplasms; Cholangiocarcinoma
Intervention: MVT-5873; pancreatectomy or hepatectomy
Intervention description: 1 mg/kg or 3 mg/kg for pre-operative dose, 1 mg/kg during post-operative period; Pancreatectomy or hepatectomy
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Well Tolerated Agent; Pancreas and Liver Resections; Recurrence-Free Survival

Summary:

      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.
    

Eligibility criteria:

        -  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 institutional upper limit of normal

                    -  Liver abnormalities in this range are consistent with pancreas cancer
                       destruction from the tumor.

          -  The effects of MVT-5873 (HuMab-5B1) on the developing human fetus are unknown. For
             this reason, women of child-bearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation and for 3 months after completion of
             study treatment. Should a woman become pregnant or suspect she is pregnant while she
             or her partner is participating in this study, she should inform her treating
             physician immediately.

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

          -  Subjects must agree to co-enrollment on the tissue collection protocol 13C0176, Tumor,
             Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection
             of Solid Tumors.

        EXCLUSION CRITERIA:

          -  Presence of disease outside the confines of a standard operation for subjects with
             periampullary cancers (pancreatic and cholangiocarcinoma).

          -  Presence of disease outside the liver for subjects with intrahepatic/hilar
             cholangiocarcinoma or metastatic colorectal cancer, other than a primary tumor for
             subjects with metastatic colorectal cancer.

          -  Subjects who are receiving any other investigational agents.

          -  Fewer than 28 days (or 5 half-lives for systemic agents, whichever is shorter) from
             the last day of prior anticancer therapy, including chemotherapy, hormonal,
             investigational, and or biological therapies and irradiation.

          -  Uncontrolled inter-current 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.

        -Active concurrent malignancies within the last five years other than the primary tumor

        in subjects with metastatic colorectal cancer, basal or squamous cell skin carcinoma or
        non- medullary thyroid carcinoma.

          -  Pregnant women are excluded from this study because of the potential for teratogenic
             or abortifacient effects of the MVT-5873. Because there is an unknown but potential

          -  Subjects with active, Hepatitis B or C infection because of the potential for
             increased liver toxicity given the damaging effects of the virus.

          -  Allergic to chimeric, humanized or human antibodies.

          -  Received live vaccine within 4 weeks prior to first date of study intervention.

          -  Infection requiring hospitalization or herpes zoster treatment within 2 weeks prior to
             the first date of study intervention.

          -  Long-term infectious diseases (tuberculosis, fungal infections) active within 2 years
             prior to the first date of study intervention.