Patient case: 45-year-old female with colon cancer; genetic feature: ERBB2 amplification

Clinical trial: Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer

Summary: This pilot phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Personalized peptide vaccine is a vaccine developed from patient's own tumor cells and blood in order to use as a biological therapy. Biological therapies, such as personalized peptide vaccine may attack tumor cells and stop them from growing or kill them.

Detailed description: PRIMARY OBJECTIVES:
  I. Demonstrate that developing a custom vaccine for metastatic pancreatic ductal adenocarcinoma (PDA) and colorectal cancer (CRC) patients is feasible.
  II. Show that a custom peptide-based vaccine in combination with pembrolizumab is safe.
  SECONDARY OBJECTIVES:
  I. Determine preliminary clinical efficacy. II. Demonstrate the antigenicity of each vaccine.
  OUTLINE:
  Patients receive personalized synthetic tumor-associated peptide vaccine therapy subcutaneously (SC) on day 1 of weeks 0, 1, 3, 4 and 6, then every 3 weeks until week 30, then at weeks 39 and 51. Beginning 30 minutes after each vaccine is administered, patients then receive imiquimod cream topically after 30 minutes. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses with pembrolizumab repeat every 3 weeks until week 51 in the absence of disease progression or unacceptable toxicity.
  After completion of study treatment, patients are followed up 2 times in 6 months.

Eligibility: Inclusion Criteria:
  -  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)
  -  Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest; vaccination will not take place until at least one line of standard chemotherapy is given
  -  Patients must have adequate fresh or frozen tissue available; if tissue is needed, then subjects may have had it collected previously under protocol PA15-0176
  -  Eastern Cooperative Oncology Group (ECOG) performance status < 1 (Karnofsky > 70%)
  -  Life expectancy of greater than 6 months
  -  Leukocytes >= 3,000/mcL
  -  Absolute neutrophil count (ANC) >= 1,000/mcL
  -  Platelets >= 75,000/mcL
  -  Total bilirubin =< 2.0 x institutional upper limit of normal
  -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (except in Gilbert's disease where direct bilirubin will be used)
  -  Calculated creatinine clearance >= 50 mL/min/1.73 m^2
  -  Patients must demonstrate an ability to understand and the willingness to sign a written informed consent document
  -  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 > 120 days after the study; abstinence is also an acceptable form of birth control
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): ECOG performance status =< 2 (Karnofsky >= 60%)
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): life expectancy of greater than 4 months
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): patients must have either measurable disease per Response Criteria in Solid Tumors (RECIST) version (v)1.1 or evaluable disease defined as an elevated tumor biomarker (CA19-9, carcinoembryonic antigen [CEA] or circulating free deoxyribonucleic acid [cfDNA] mutation); pancreatic cancer patients with an elevated tumor marker following a primary pancreatic surgery would be eligible
  Exclusion Criteria:
  -  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
  -  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
  -  Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (ribonucleic acid or hepatitis C virus [HCV] antibody) indicating acute or chronic infection
  -  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
  -  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
  -  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
  -  Women of child bearing potential who are pregnant or breastfeeding; women with a positive pregnancy test at enrollment or prior to administration of vaccine
  -  Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
  -  Known history of active TB (Bacillus tuberculosis)
  -  Hypersensitivity to pembrolizumab or any of its excipients
  -  Has a known additional malignancy that is progressing or requires active treatment
  -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): patients who have had chemotherapy or radiotherapy within 2 weeks prior to first treatment or those who have not recovered to baseline from adverse events due to agents administered more than 2 weeks earlier (washout period)
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS):
  -  Women of child bearing potential who are pregnant or breastfeeding
  -  Women with a positive pregnancy test prior to administration of vaccine
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): 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
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): patients may not be receiving any other investigational agents within 2 weeks prior to first treatment
  -  JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): in addition to above exclusion criteria unless specified differently below: has received a live vaccine within 30 days of planned start of study therapy; NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Relevance to patient case: not relevant