Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing

• INCLUSION PART I
• Adults greater than or equal to 18 with recurrent or progressive, metastatic solid tumors characterized by some HER2/neu expression that have failed standard therapies with known benefit but for whom trastuzumab is not clinically indicated:
• Patients with ovarian, colon, non-small cell lung, renal cell, bladder and prostate cancer that are known to be HER2 1+, 2+ or 3+ by IHC OR have a Vysis FISH result greater than 1.8.
• Patients with breast cancer that is known to be HER2 1+ or 2+ by IHC or with a Vysis FISH result of 1.8 - less than 2.2.
• Adults greater than or equal to 18 with HER2+ bladder cancer in the adjuvant setting (adjuvant bladder cancer patients):
• Tumor stage T3a, T3b, T4a, T4b and any node positive disease regardless of tumor stage.
• Tumors that are HER2 1+, 2+ or 3+ by IHC or have a Vysis FISH result greater than 1.8.
• Status-post primary cystectomy with curative intent.
• May or may not have received neoadjuvant cisplatin-based combination chemotherapy per NCCN guidelines.
• May or may not have received adjuvant radiotherapy or chemotherapy based on pathologic risk per NCCN guidelines.
• Greater than or equal to 6 weeks s/p primary surgery with curative intent.

2.1.1.3 Life expectancy of greater than or equal to 6 months,

• Performance Status: ECOG 0-1.
• Naive to trastuzumab, pertuzumab and lapatnib or other investigational HER2-directed therapies (e.g. T-DM1).
• Recurrent or progressive disease on prior standard therapies with known clinical benefit (except adjuvant bladder cancer population).
• For adults with recurrent, metastatic solid tumors: presence of measurable disease, defined as at least one lesion that can be accurately measured by CT scan in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques and/or measurable, clinically visible skin lesions, with the exception of metastatic bladder cancer patients that have completed first line chemotherapy and may not have measurable disease.
• Baseline LVEF by 2D Echocardiogram greater than or equal to 55%.
• Greater than or equal to 2 weeks since standard or investigational treatment for metastatic disease.
• Stable, concurrent use of tamoxifen or aromatase inhibitors for ER+ status allowed.
• Hematologic parameters: ANC greater than or equal to 1000 cells/mm(3), ALC greater than or equal to 500 cells/mm(3), Hemoglobin greater than or equal to 9.0 gm/dL, WBC greater than or equal to 2,500 cells/mm(3), platelet count greater than or equal to 75,000/mm3, PT/PTT less than or equal to 1.5 times the upper limits of normal.
• Chemistry parameters: SGOT and SGPT less than or equal to 3 times the upper limits of normal and total bilirubin less than or equal to1.5 mg/dl, Alk PO4 less than or equal to 2 times the upper limits of normal (except for patients with documented metastatic disease to bone).
• Negative serum HCG if female and of childbearing potential.
• Negative serology for HIV-1.
• Negative serology for hepatitis B and C unless the result is consistent with prior vaccination or prior infection with full recovery.
• Willingness of female and male subjects to use effective contraception e.g. oral contraceptives, barrier device, intrauterine device, or condoms, during the study and for three months following the last dose of study vaccine. We suggest that subjects do not become pregnant or father a child during the study, and for 3 months following receipt of the investigational AdHER2 DC vaccine. (FDA requested language)
• Able to understand and provide Informed Consent.

INCLUSION PART II:

• Age greater than or equal to 18 years
• Breast cancer patients with 3+ HER2/neu expression by IHC or a Vysis FISH result greater than 2.2.
• Recurrent or progressive metastatic disease after at least 1-2 courses of standard therapies with known clinical benefit i.e. trastuzumab or lapatinib, ado-trastuzumab emtansine (TDM1) or other investigational HER2-directed therapies (e.g. MGAH22).
• Life expectancy of greater than or equal to 6 months.
• Performance Status: ECOG 0-1.
• Presence of measurable disease, defined as at least one lesion that can be accurately measured by CT scan in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques and/or measurable clinical visible skin lesions.
• Baseline LVEF by 2D Echocardiogram greater than or equal to 55%.
• Greater than or equal to 2 weeks since receipt of standard or investigational HER2- directed therapy for metastatic or recurrent disease.
• Stable, concurrent use of tamoxifen or aromatase inhibitors for ER+ status allowed.
• Hematologic parameters: ANC greater than or equal to 1000 cells/mm(3), ALC greater than or equal to 500 cells/mm(3), absolute Hemoglobin greater than or equal to 9.0 gm/dL, WBC greater than or equal to 2,500 cells/mm(3), platelet count greater than or equal to 75,000/mm(3), PT/PTT less than or equal to 1.5 times the upper limits of normal.
• Chemistry parameters: SGOT and SGPT less than or equal to 3 times ULN, total bilirubin less than or equal to 1.5 times ULN and Alk PO4 less than or equal to 2 times ULN (except for patients with documented metastatic disease to bone).
• Negative serum HCG if of childbearing potential.
• Negative serology for HIV-1.
• Negative serology for hepatitis B and C unless the result is consistent with prior vaccination or prior infection with full recovery.
• Willingness of female subjects to use effective contraception e.g. oral contraceptives, barrier device, intrauterine device, or condoms, during the study and for three months following the last dose of study vaccine. We suggest that subjects do not become pregnant during the study, and for 3 months following receipt of the investigational AdHER2 DC vaccine. (FDA requested language)
• Able to understand and provide Informed Consent.

EXCLUSION CRITERIA:

• Females who are pregnant or breastfeeding.
• Patients with active or previously treated CNS metastases or leptomeningeal involvement by tumor.
• Patients with rapidly progressing disease in the opinion of the Principal Investigator.
• Patients requiring scheduled opiod narcotics for cancer-related pain. (requested by FDA)
• Patients with inadequate bilateral peripheral venous access for the required apheresis to allow generation of the autologous AdHER2 DC vaccine product.
• Clinically significant cardiac dysfunction defined as a history of greater than or equal to NYHA Class II symptoms, angina, myocardial infarction or cardiac arrhythmias requiring treatment or discontinuation of chemotherapy.
• History of changes in baseline LVEF that occurred during prior treatment with trastuzumab.
• Cumulative doxorubicin dose greater than or equal to 400mg/m(2) or cumulative epirubicin dose greater than or equal to 800mg/m(2).
• Use of any standard chemotherapy or other investigational agent(s) within 2 weeks of study enrollment.
• Use of systemic corticosteroid therapy within 2 weeks of study enrollment, including patients receiving replacement corticosteroid therapy. Note: only topical, inhaled and intranasal steroid therapy is permitted.
• Active systemic viral, bacterial or fungal infection requiring treatment.