Clinical trial NCT02018458: Safety Study Of Chemotherapy Combined With Dendritic Cell Vaccine to Treat Breast Cancer
Official title: Pilot Safety Trial of Preoperative Chemotherapy Combined With Dendritic Cell Vaccine in Patients With Locally Advanced, Triple-Negative Breast Cancer or ER-Positive, Her2-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Dendritic cell vaccine
Breast Cancer
Doxorubicin
Paclitaxel
Cyclophosphamide
Carboplatin
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2013-12-23
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the safety and feasibility of combining cyclin B1/WT-1/CEF (antigen)-loaded DC vaccination with preoperative chemotherapy.

The secondary objectives of this trial are to determine pathologic complete response rates; disease-free survival; to assess immune biomarkers of immunity (antigen-specific CD8+ T cell immunity and TH2 T cells) in breast cancer biopsy specimens and blood samples in patients receiving DC vaccinations; and to assess the feasibility of immunizing LA TNBC and ER+/HER2- BC patients with patient-specific tumor antigens.

Detailed description: Recent studies have shown that human breast cancers can be immunogenic, and that enhancing the immune effector function already present may augment the cytotoxic effects of standard therapies.

vaccination remains the most attractive strategy because of its expected inducement of both therapeutic T cell immunity (effector T cells) and protective T cell immunity (tumor-specific memory T cells that can control tumor relapse). Several clinical studies have now demonstrated that immunity against tumor antigens can be enhanced in cancer patients by vaccination with ex vivo-generated tumor antigen-loaded dendritic cells (DCs). This strategy capitalizes on the unique capacity of DCs to prime lymphocytes and to regulate and maintain immune responses.

Our goals are to boost T cell immunity targeted against breast cancer utilizing a tumor antigen-loaded DC vaccine, to enhance chemotherapy effectiveness and decrease tumor metastagenicity, and to decrease the recurrence rates of LA TNBC and ER+/HER2- BC. Patients will be treated with a combination of antigen-loaded DC vaccinations along with standard preoperative chemotherapy, to improve immunogenicity and to increase the pCR rate achieved with standard therapy. The trial will consist of 2 patient cohorts: TNBC and ER+/HER2- BC.

Eligibility criteria: - Inclusion Criteria:

A patient will be considered for enrollment in this study if all of the following criteria are met:

1. Female patients ≥18 years of age.
2. Have either:

   1. locally advanced TNBC defined as invasive ductal cancer; ER- tumors with \<10% of tumor nuclei immunoreactive; PR- tumors with \<10% of tumor nuclei immunoreactive; T3 or T4 disease, regardless of nodal status (T2 disease is eligible if there are positive lymph nodes present by physical exam or imaging evaluation or histological evaluation, OR
   2. High-risk ER+ breast cancer defined as grade 3 invasive ductal or mixed ductal/lobular cancers, or grade 2 with Ki67 ≥20%; node positive as evidenced by physical exam or imaging evaluation or histological evaluation.
3. HER2- negative breast cancer. If HER2-, it is defined as follows:

   1. FISH-negative (FISH ratio \<2.0), or
   2. IHC 0-1+, or
   3. IHC 2+ AND FISH-negative (FISH ratio\<2.0)
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
5. Adequate hematologic function, defined by:

   1. Absolute neutrophil count (ANC) \>1500/mm3
   2. Platelet count ≥100,000/mm3
   3. Hemoglobin \>9 g/dL (in the absence of red blood cell transfusion)
6. Adequate liver function, defined by:

   1. AST and ALT ≤2.5 x the upper limit of normal (ULN)
   2. Total bilirubin ≤1.5 x ULN
7. Adequate renal function, defined by:

   a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥60 ml/min
8. Patients with previous history of invasive cancers (including breast cancer) are eligible if definitive treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease.
9. Eligible for treatment with paclitaxel, doxorubicin, cyclophosphamide and carboplatine.
10. Patient must be accessible for treatment and follow-up.
11. Patients must be willing to undergo research biopsies to obtain breast cancer tissue for whole exome sequencing and evaluation of tumor immune microenvironment.
12. All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.

    * Exclusion Criteria:

A patient will be ineligible for inclusion in this study any of the following criteria are met:

1. Evidence of metastatic disease on bone scan and CT scan of chest/abdomen (or PET CT scan). Patients with intrathoracic metastatic adenopathy are eligible.
2. Active infection or unexplained fever \>38.5°C during screening.
3. Active infections including viral hepatitis and HIV.
4. Active asthma or other condition requiring steroid therapy.
5. Autoimmune disease including lupus erythematosus or rheumatoid arthritis. Topical or inhaled corticosteroids are allowed.
6. Patients who are currently receiving or who have received previous systemic therapy for breast cancer (eg, chemotherapy, antibody therapy, targeted agents).The use of an LHRH agonist during chemotherapy in premenopausal women who wish to preserve ovarian function is allowed, but is not required.
7. Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
8. Have a NYHA Class III or IV CHF or LVEF \<55%. Patients with significant cardiac disease history within 1 year or ventricular arrhythmias requiring medication are also excluded.
9. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as:

   1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
   2. uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
   3. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
10. History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or that might affect interpretation of the results of this study, or render the patient at high risk for treatment complications.
11. Any other investigational or anti-cancer treatments while participating in this study.
12. Any other cancer

Primary outcomes:
measure: Safety of DC Vaccine Combined With Chemotherapy
timeFrame: 4 years
Secondary outcomes:
measure: Pathologic Complete Response Rate
timeFrame: 1 year
measure: Disease-free Survival
timeFrame: 36 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: Baylor Health Care System
name: Joyce O'Shaughnessy, MD
role: PRINCIPAL_INVESTIGATOR
References: