Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
Condition: Neoplasms; Prostate Cancer; Lung Cancer; Breast Cancer; Colon Cancer
MeSH terms: Colonic Neoplasms
Intervention: ETBX-051; adenoviral brachyury vaccine; ETBX-061; adenoviral Mucin-1 (MUC1) vaccine; ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine
Intervention description: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year; immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year; immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Combination Vaccine; Adenoviral; ETBX-011; ETBX-061; ETBX-051

Summary:

      Background:

      ETBX-011, ETBX-061, and ETBX-051 are cancer vaccines. Their goal is to teach the immune
      system to target and kill cancer cells. The vaccines target 3 proteins found in many types of
      cancer. Researchers think targeting all 3 proteins in unison will have the best results.

      Objective:

      To test the safety of combining ETBX-011, ETBX-061, and ETBX-051 and their effects on the
      immune system.

      Eligibility:

      People ages 18 and older with advanced cancer that has not responded to standard therapies

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood, urine, and heart tests

      Scan: They will lie in a machine that takes pictures of the body.

      Participants will receive the 3 vaccines through 3 shots under the skin every 3 weeks for 3
      doses, then every 8 weeks for up to 1 year. They will have blood and urine tests at each
      vaccine visit. They will have scans and other measurements of their tumor after 9 weeks and
      then at their vaccine visits every 8 weeks.

      Participants will keep a diary of symptoms at the injection site.

      Participants will have a visit 90 days after their final treatment. This will include a
      physical exam and blood and urine tests. If they have any ongoing side effects, they will be
      followed until these end or are not changing.

      After this visit, they will be called every 3 months for the first year, every 6 months for
      the next 2 years, then every 12 months for another 2 years to see how they are doing.

      Participants will have the option to enroll in a long-term follow-up study.

      ...
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Age greater than or equal to 18 years (male and female).

          -  Ability to understand and provide signed informed consent that fulfills Institutional
             Review Board (IRB)'s guidelines.

          -  Subjects with cytologically or histologically confirmed locally advanced or metastatic
             solid tumor malignancy.

          -  Subjects must have completed or had disease progression on at least one prior line of
             disease-appropriate therapy or not be candidates for therapy of proven efficacy for
             their disease.

          -  Subjects may have measurable or non-measurable but evaluable. Subjects with surgically
             resected locally advanced or metastatic disease at high risk of relapse are also
             eligible.

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1.

          -  Subjects who have received prior carcinoembryonic antigen (CEA), mucin-1 (MUC1),
             and/or Brachyury-targeted immunotherapy (vaccine) are eligible for this trial if this
             treatment was discontinued at least 4 weeks prior to enrollment.

          -  Resolution of clinically significant side effects of prior chemotherapy, radiotherapy,
             immunotherapy or surgical procedures to National Cancer Institute (NCI) Common
             Terminology Criteria in Adverse Events (CTCAE) Grade less than or equal to 1 or grade
             less than or equal to 2 for neuropathy.

               -  Adequate hematologic function at screening, as follows:

               -  Absolute neutrophil count (ANC) >= 1 x 10^9/L

               -  Hemoglobin >= 9 g/dL

               -  Platelets >= 75,000/mcL.

          -  Adequate renal and hepatic function at screening, as follows:

               -  Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR
                  creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula
                  below):

                    -  Female CrCl = ((140 - age in years) x weight in kg x 0.85) / (72 x serum
                       creatinine in mg/dL)

                    -  Male CrCl = ((140 - age in years) x weight in kg x 1.00)/ 1.00) / (72 x
                       serum creatinine in mg/dL)

               -  Bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilbert's syndrome,
                  a total bilirubin less than or equal to 3.0 x ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
             to 2.5 x ULN, unless liver metastases are present, then values must be less than or
             equal to 3 x ULN)

          -  The effects of the combination ETBX-011, ETBX-051, ETBX-061 vaccine regimen on the
             developing human fetus are unknown. For this reason, female subjects of childbearing
             potential defined as any female who has experienced menarche and who has not undergone
             surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or
             who is not postmenopausal (menopause being defined clinically as 12 months of
             amenorrhea in a woman over 45 in the absence of other biological or physiological
             causes) and male patients who are not surgically sterile (vasectomy etc.), must agree
             to use acceptable contraceptive methods for the duration of the study and for one
             month after the last vaccination. Acceptable forms of contraception include oral
             contraceptives, intrauterine device, condom or vaginal diaphragm plus spermicidal
             (gel/foam/cream/vaginal suppository), or total abstinence.

          -  Ability to attend required study visits and return for adequate follow up, as required
             by this protocol.

        EXCLUSION CRITERIA:

          -  Pregnant and nursing women. Because there is an unknown but potential risk for adverse
             events in nursing infants secondary to treatment of the mother with combination
             ETBX-011, ETBX-051, ETBX-061, breastfeeding should be discontinued if the mother is
             treated with combination ETBX-011, ETBX-051, ETBX-061. These potential risks may also
             apply to other agents used in this study.

          -  There should be a minimum of 4 weeks from any prior investigational drug,
             chemotherapy, immunotherapy, with the exception of hormonal therapy for prostate and
             breast cancers, human epidermal growth factor receptor 2 (HER2-) directed therapy for
             HER2+ breast or stomach cancer (3+ immunohistochemistry (IHC) or fluorescence in situ
             hybridization (FISH+), drugs targeting epidermal growth factor receptor (EGFR),
             anaplastic large-cell lymphoma kinase (ALK) or ROS1 in EGFR,ALK, ROS1-mutated lung
             cancer, respectively, or standard maintenance therapies for any solid tumor under the
             condition that subjects are on these therapies for at least two months before start of
             trial treatment.

          -  There should also be a minimum of 4 weeks from any prior radiotherapy except for
             palliative bone directed therapy.

          -  Known active brain or central nervous system metastasis (less than 1 month out from
             definitive radiotherapy or surgery), or seizures requiring anticonvulsant treatment,
             or clinically significant cerebrovascular accident or transient ischemic attack (<3
             months).

          -  Subjects with active autoimmune disease requiring systemic immunosuppressive treatment
             within the past 4 weeks such as but not restricted to inflammatory bowel disease,
             systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple
             sclerosis. A history of autoimmune disease which is not active nor has required recent
             systemic immunosuppressive therapy (< 4 weeks prior to enrollment) is not reason for
             exclusion.

          -  Subjects with serious intercurrent chronic or acute illness, such as cardiac or
             pulmonary disease, hepatic disease, or other illness considered by the Investigator as
             high risk for investigational drug treatment.

          -  Subjects with clinically significant heart disease, such as congestive heart failure
             (class II, III, or IV defined by the New York Heart Association functional
             classification), history of unstable or poorly controlled angina, or history (< 1
             year) of ventricular arrhythmia.

          -  Subjects with a medical or psychological impediment that would impair the ability of
             the subject to receive therapy per protocol or impact ability to comply with the
             protocol or protocol-required visits and procedures.

          -  History of second malignancy within 3 years prior to enrollment except for the
             following: adequately treated non-melanoma skin cancer, cervical carcinoma in situ,
             superficial bladder cancer or other localized malignancy after discussion with the
             medical monitor.

          -  Presence of a known active acute or chronic infection, including human
             immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay
             (ELISA) and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV,
             as determined by hepatitis B surface antigen (HBsAg) and hepatitis C serology).

          -  Subjects on systemic intravenous or oral corticosteroid therapy with the exception of
             physiologic doses of corticosteroids (less than or equal to the equivalent of
             prednisone 10 mg/day) or other immunosuppressives such as azathioprine or cyclosporin
             A are excluded on the basis of potential immune suppression. For these subjects these
             excluded treatments must be discontinued at least 2 weeks prior to enrollment for
             recent short course use (less than or equal to 14 days) or discontinued at least 4
             weeks prior to enrollment for long term use (> 14 days). In addition, the use of
             corticosteroids as premedication for contrast-enhanced studies is allowed prior to
             enrollment and on study.

          -  Subjects with known allergy or hypersensitivity to any component of the
             investigational product will be excluded.

          -  Subjects with acute or chronic skin disorders that will interfere with injection into
             the skin of the extremities or subsequent assessment of potential skin reactions will
             be excluded.

          -  Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist(R)) or a killed
             (inactivated)/subunit vaccine (e.g., PNEUMOVAX(R), Fluzone(R)) within 28 days or 14
             days, respectively, of the first planned dose of ETBX vaccine.