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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Baylor Research Institute
Sponsor:
Information provided by (Responsible Party):
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT02018458
First received: December 4, 2013
Last updated: June 22, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Biological: LA TNBC: DC vaccine+Preop chemo
Biological: ER+/HER2-BC:DC vaccine+Preop chemo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • Safety of DC vaccine combined with chemotherapy, and DC vaccine combined with chemotherapy [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Toxicities in both groups will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 . Includes 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:
  • Pathologic complete response rate with DC vaccine [ Time Frame: 4 year ] [ Designated as safety issue: No ]
    Patients will undergo surgical resection of residual breast and axillary malignant tissue after protocol-directed treatment. The pathologic specimen will be graded according to the tumor regression grading schema called the Residual Cancer Burden (RCB).

  • Disease free survival with DC vaccine [ Time Frame: 4 year ] [ Designated as safety issue: No ]
    Analysis of disease free survival in both groups will be done using standard & established statistical methods.


Estimated Enrollment: 20
Study Start Date: May 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LA TNBC: DC vaccine+Preop chemo
LA TNBC patients will receive standard preop AC followed by TCb chemo for 24 weeks. Chemo and DC vaccinations will be given intratumoral and subcutaneous for 4 times prior surgery. During the AC cycles, vaccines will be given on any day between Days 9-12 of Cycles 1 and 3 of AC. Vaccines will be given on any day between Days 11-15 of Cycles 1 and 3 of TCb. Patients will undergo biopsies of their cancer prior to treatment and 1-2 days prior to or on Day 1 of Cycle 4 of AC. After this, patients will have surgery, locoregional radiation therapy to the breast or chest wall and regional lymphatics per standard of care, and will receive 3 boost DC vaccinations subcutaneously, rotating injection sites in the upper arm. The 1st vaccination will occur after the surgery and prior to radiation; 2nd will occur 30 days ± 3 days after radiation; the 3rd will occur 90 days ± 3 days after the 2nd boost.
Biological: LA TNBC: DC vaccine+Preop chemo
LA TNBC patients will receive standard preop AC followed by TCb chemo for 24 weeks. Chemo and DC vaccinations will be given intratumoral and subcutaneous for 4 times prior surgery. During the AC cycles, vaccines will be given on any day between Days 9-12 of Cycles 1 and 3 of AC. Vaccines will be given on any day between Days 11-15 of Cycles 1 and 3 of TCb. Patients will undergo biopsies of their cancer prior to treatment and 1-2 days prior to or on Day 1 of Cycle 4 of AC. After this, patients will have surgery, locoregional radiation therapy to the breast or chest wall and regional lymphatics per standard of care, and will receive 3 boost DC vaccinations subcutaneously, rotating injection sites in the upper arm. The 1st vaccination will occur after the surgery and prior to radiation; 2nd will occur 30 days ± 3 days after radiation; the 3rd will occur 90 days ± 3 days after the 2nd boost.
Other Names:
  • DC Vaccine - Dendritic Cell Vaccine
  • Preop chemo: Doxorubicin
  • Preop chemo: cyclophosphamide
  • Preop chemo: Paclitaxel
  • Preop chemo: Carboplatin
Experimental: ER+/HER2-BC:DC vaccine+Preop chemo
ER+/HER2- BC patients will receive standard preop AC followed by weekly T given for 22 weeks. Chemo and DC vaccinations will be given intratumoral and subcutaneous, for 4 times prior surgery. During the AC cycles, vaccines will be given any day between Days 9-12 of Cycles 1 and 3 of AC. Vaccines will be given on Day 1 during Cycle 2 or Cycle 3 and on Day 1 during either Cycle 8 or Cycle 9 of T. Vaccine will be given after T infusion is completed. Patients will undergo biopsies of their cancer prior to treatment and 1-2 days prior to or on Day 1 of Cycle 4 of AC. Patients will have surgery, locoregional radiation therapy to the breast or chest wall and regional lymphatics per standard of care, and will receive 3 boost DC vaccinations subcutaneously, rotating injection sites in the upper arm. The 1st vaccination will occur after surgery and prior to radiation; the 2nd will occur 30 days ± 3 days after radiation; and the 3rd will occur 90 days ± 3 days after the 2nd boost.
Biological: ER+/HER2-BC:DC vaccine+Preop chemo
ER+/HER2- BC patients will receive standard preop AC followed by weekly T given for 22 weeks. Chemo and DC vaccinations will be given intratumoral and subcutaneous, for 4 times prior surgery. During the AC cycles, vaccines will be given any day between Days 9-12 of Cycles 1 and 3 of AC. Vaccines will be given on Day 1 during Cycle 2 or Cycle 3 and on Day 1 during either Cycle 8 or Cycle 9 of T. Vaccine will be given after T infusion is completed. Patients will undergo biopsies of their cancer prior to treatment and 1-2 days prior to or on Day 1 of Cycle 4 of AC. Patients will have surgery, locoregional radiation therapy to the breast or chest wall and regional lymphatics per standard of care, and will receive 3 boost DC vaccinations subcutaneously, rotating injection sites in the upper arm. The 1st vaccination will occur after surgery and prior to radiation; the 2nd will occur 30 days ± 3 days after radiation; and the 3rd will occur 90 days ± 3 days after the 2nd boost.
Other Names:
  • DC Vaccination - Dendritic cell vaccination
  • Preop chemo - doxorubicin
  • Preop chemo - cyclophosphamide
  • Preop chemo - paclitaxel
  • Preop chemo: Carboplatin

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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:

a. AST and ALT ≤2.5 x the upper limit of normal (ULN) b. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02018458

Contacts
Contact: Grace Townsend 2148188382 grace.townsend@baylorhealth.edu
Contact: Silviya Meletath 2148204987 silviya.meletath@baylorhealth.edu

Locations
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75246
Principal Investigator: Joyce O' Shaughnessy, MD         
Sub-Investigator: Karolina Palucka, PhD         
Sponsors and Collaborators
Baylor Research Institute
Investigators
Principal Investigator: Joyce O' Shaughnessy, MD Baylor Health Care System
  More Information

No publications provided

Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT02018458     History of Changes
Other Study ID Numbers: 013-154
Study First Received: December 4, 2013
Last Updated: June 22, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:
Dendritic cell vaccine
Breast Cancer
Doxorubicin
Paclitaxel
Cyclophosphamide
Carboplatin

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Carboplatin
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on August 03, 2015