Brief Title
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
Official Title
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
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants With Disease Recurrence At 1 Year
Secondary Outcome
Define Disease Free Survival (DFS) for Participants Treated With Preoperative MVT-5873
Condition
Colon Cancer
Intervention
MVT-5873
Study Arms / Comparison Groups
Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1)
Description: Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
10
Start Date
November 13, 2019
Completion Date
May 27, 2022
Primary Completion Date
May 27, 2022
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jonathan M Hernandez, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03801915
Organization ID
190039
Secondary IDs
19-C-0039
Responsible Party
Principal Investigator
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Jonathan M Hernandez, M.D., Principal Investigator, National Cancer Institute (NCI)
Verification Date
February 2023