Safety Study Of Chemotherapy Combined With Dendritic Cell Vaccine to Treat Breast Cancer

Phase 1

Completed

• Conditions: Breast Cancer

• Registration Number: NCT02018458
• Lead Sponsor: Baylor Research Institute

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.

Study Timeline

• Study First Submitted: 2013-12-04
• Study First Submitted QC: 2013-12-17
• Study First Posted: 2013-12-23
• Study Start: 2014-05
• Primary Completion: 2019-09-18
• Study Completion: 2019-09-18
• Results First Submitted: 2020-02-28
• Results First Submitted QC: 2020-02-28
• Results First Posted: 2020-03-13
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-07
• Last Update Posted: 2021-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Safety of DC Vaccine Combined With Chemotherapy	4 years	Toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 . This will include all patients (eligible and ineligible) who receive at least 1 inoculation of DC vaccine therapy. This safety population will also be used for the summaries and analysis of all safety parameters (drug exposure, tables of adverse events information, including serious adverse events, etc.).

Secondary Outcome Measures

Name	Time	Method
Pathologic Complete Response Rate	1 year	Results are only reported for Arm 1, "LA TNBC: DC vaccine+preop chemo patients". Arm 2 did not enroll any patients.; The pathologic specimen will be graded per the tumor regression grading schema provided by the University of Texas MD Anderson Cancer Center "Residual Cancer Burden Calculator" at http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3. The following parameters are required from pathologic examination in order to calculate RCB: largest 2 dimensions of residual tumor bed in the breast; entire largest cross-sectional area of residual tumor bed; percentage of the tumor bed area that contains carcinoma; percentage of carcinoma in tumor bed that is in situ; number of positive (metastatic) lymph nodes; largest diameter of largest nodal metastasis. A pathologic complete response is defined as NO pathologic evidence of invasive disease in the breast or axillary lymph nodes. RCB-I (minimal cancer burden); RCB-II (moderate burden); and RCB-III (extensive burden).
Disease-free Survival	36 months	Results are only reported for Arm 1, "LA TNBC: DC vaccine+preop chemo patients". Arm 2, "ER+/HER2- BC: DC vaccine+preop chemo patients" did not enroll any patients with these hormone receptor criteria.; Analysis of disease-free survival ("DFS", reported in months) was calculated from the first day of treatment up to 36 months.

Trial Locations

Locations (1)

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States