Patient case: 73-year-old female with Pancreatic ductal adenocarcinoma. Genetic variant: ERBB3. Other conditions: Whipple, FNA.

Clinical trial: Peptide Vaccine in Advanced Pancreatic Ductal Adenocarcinoma or Colorectal Adenocarcinoma

Summary: The goal of this clinical research study is to learn if it is possible to make a vaccine for advanced pancreatic or colorectal cancer. The safety of this vaccine will also be studied.
  This study will use your tumor cells (either from a fresh biopsy or from leftover tissue samples) and blood to help create a vaccine designed specifically for you based on what the study doctor and research staff can learn about the type of mutated proteins (a type of genetic change) in the tumor.

Detailed description: Tissue Collection:
  Within 4 weeks after signing this informed consent document, as part of the screening tests:
  -  You will have leftover frozen tissue collected to create your vaccine, if available. If there is not enough frozen tissue available, then leftover tissue from a recent procedure performed as part of your standard of care will be collected. The study study staff may ask you to take part in another MD Anderson clinical research study (PA15-0176) for collection of leftover tissue. The study doctor will discuss this with you and, if you decide to take part, you will sign a separate informed consent document.
  After the tissue cells have been collected, your vaccine will be made.
  The vaccine can also be made from blood cells. If you agree, you will be consented and enrolled under a separate protocol, PA14-0138, to have the leukapheresis procedure performed. Leukapheresis is a special type of blood draw procedure that separates the red blood cells, white blood cells, and other parts of your blood from each other. The consent form for this protocol will explain how the leukapheresis procedure is performed and its risks. The white blood cells collected from leukapheresis will be used in this study.
  Baseline Tests:
  You must receive at least 1 type of chemotherapy after you are enrolled in this study but before your first dose of vaccine. There is no limit to the number of types of chemotherapy you may receive. Your study doctor will decide when you will enter the treatment part of this study.
  Within 28 days after your last dose of chemotherapy:
  -  You will have a physical exam.
  -  Blood (about 2 tablespoons) will be drawn for routine tests. The routine blood draw will include a pregnancy test if you can become pregnant.
  Within 14 days before your first dose of vaccine, you will have an MRI or CT scan of the chest, abdomen, and pelvis.
  Study Vaccine Administration:
  About 28 days after your last dose of chemotherapy, you will receive the vaccine as an injection under the skin on Day 1 of Weeks 0, 3, 6, and 9.
  Imiquimod cream will be applied over the injection site about 30 minutes after you receive the vaccine. This will be done each time you receive the vaccine.
  Study Visits:
  On Day 1 of Weeks 0, 3, 6, 9:
  -  You will have a physical exam.
  -  Blood (about 6 tablespoons) will be drawn for routine tests and to test for genetic mutations.
  -  During Week 6 only, you will have an MRI or CT scan of the chest, abdomen, and pelvis.
  On Day 1 of Weeks 12 and 20, blood (about 4 tablespoons) will be drawn to test for genetic mutations.
  On Day 1 of Week 16:
  -  You will have a physical exam.
  -  Blood (about 2 tablespoons) will be drawn for routine tests.
  Length of Study:
  You may receive the vaccine for up to 9 weeks. You may be able to continue receiving the vaccine after Week 9, if the disease is stable or appears to be getting better. The study doctor will discuss this with you.
  You will no longer be able to receive the study vaccine if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
  Your participation on the study will be over after follow-up.
  End-of-Study Visit:
  About 8 weeks after your last study visit:
  -  You will have a physical exam.
  -  Blood (about 2 tablespoons) will be drawn for routine tests.
  Follow-Up:
  You will be called 2 times by the study staff in the 6 months after your last dose of vaccine and asked about any side effects you may have experienced since the end-of-study visit. Each call should last about 10 minutes.
  If you left the study because you had side effects, you will be called by the study staff until that side effect has gone away or has become stable.
  This is an investigational study. The study vaccine is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the vaccine is designed to work.
  Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.

Eligibility: Inclusion Criteria:
  1. Patients must have metastatic Pancreatic Ductal Adenocarcinoma (PDA) or metastatic colorectal cancer (CRC) to be eligible. (PDA patients with an elevated tumor marker following a primary pancreatic surgery would be eligible).
  2. Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest. Vaccination will not take place until after patients have been offered and failed all curative therapies for either PDA or CRC. Vaccination will not take place until at least one line of standard chemotherapy is given.
  3. Patients must have adequate fresh or frozen tissue available. If tissue is needed, then subjects may have it collected under protocol PA15-0176.
  4. Age =/>18 years.
  5. ECOG performance status <1 (Karnofsky >70%)
  6. Life expectancy of greater than 6 months.
  7. Patients must have normal organ and marrow function as defined below:: a) leukocytes =/>3,000/mcL; b) absolute neutrophil count =/>1,000/mcL; c) platelets =/>75,000/mcL; d)total bilirubin =/< 2.0 X institutional upper limit of normal; e) AST(SGOT)/ALT(SGPT) =/<2.5 X institutional upper limit of normal (except in gilberts disease where direct bilirubin will be used); f) creatinine clearance =/>50 mL/min/1.73 m^2
  8. Patients must demonstrate an ability to understand and the willingness to sign a written informed consent document.
  9. The effects of a peptide based vaccine on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception at study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Birth control specifications: unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), sexually active participants must use birth control during and for 1 month after the study. Acceptable forms of birth control include condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is also an acceptable form of birth control.
  10. Inclusion criteria just prior to first vaccination (within 21 days) in addition to above inclusion criteria unless specified differently below : ECOG performance status =/<2 (Karnofsky =/>60%)
  11. Inclusion criteria just prior to first vaccination (within 21 days): Life expectancy of greater than 4 months
  12. Inclusion criteria just prior to first vaccination (within 21 days): Patients must have measurable or evaluable disease per RECIST v1.1.
  Exclusion Criteria:
  1. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for lack of efficacy of therapeutic cancer vaccine.
  2. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  3. Known history of chronic hepatitis B or hepatitis C virus chronic infection.
  4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  6. Uncontrolled concurrent 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.
  7. Women of child bearing potential who are pregnant or breastfeeding. Women with a positive pregnancy test at enrollment or prior to administration of vaccine.
  8. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to above exclusion criteria unless specified differently below: Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered to baseline from adverse events due to agents administered more than 2 weeks earlier (washout period).
  9. Exclusion criteria just prior to first vaccination- (within 21 days) - in addition to above exclusion criteria unless specified differently below: Women of child bearing potential who are pregnant or breastfeeding. Women with a positive pregnancy test prior to administration of vaccine.
  10. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to above exclusion criteria unless specified differently below: Uncontrolled concurrent 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.
  11. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to above exclusion criteria unless specified differently below: Patients may not be receiving any other investigational agents.

Relevance to patient case: not relevant