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

NCT02018458 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 013-154
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Dendritic cell vaccine; Breast Cancer; Doxorubicin; Paclitaxel; Cyclophosphamide; Carboplatin

Outcome Measures

Primary Outcomes (1)

• Safety of DC Vaccine Combined With Chemotherapy

  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.).

  4 years

Secondary Outcomes (2)

• Pathologic Complete Response Rate

  1 year

• Disease-free Survival

  36 months

Study Arms (2)

LA TNBC: DC vaccine+Preop chemo

EXPERIMENTAL

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

ER+/HER2-BC:DC vaccine+Preop chemo

EXPERIMENTAL

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

Interventions

LA TNBC: DC vaccine+Preop chemo BIOLOGICAL

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.

Also known as: DC Vaccine - Dendritic Cell Vaccine, Preop chemo: Doxorubicin, Preop chemo: cyclophosphamide, Preop chemo: Paclitaxel, Preop chemo: Carboplatin

LA TNBC: DC vaccine+Preop chemo

ER+/HER2-BC:DC vaccine+Preop chemo BIOLOGICAL

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.

Also known as: DC Vaccination - Dendritic cell vaccination, Preop chemo - doxorubicin, Preop chemo - cyclophosphamide, Preop chemo - paclitaxel, Preop chemo: Carboplatin

ER+/HER2-BC:DC vaccine+Preop chemo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A patient will be considered for enrollment in this study if all of the following criteria are met:
• Female patients ≥18 years of age.
• Have either:
• 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
• 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.
• HER2- negative breast cancer. If HER2-, it is defined as follows:
• FISH-negative (FISH ratio \<2.0), or
• IHC 0-1+, or
• IHC 2+ AND FISH-negative (FISH ratio\<2.0)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Adequate hematologic function, defined by:
• Absolute neutrophil count (ANC) \>1500/mm3
• Platelet count ≥100,000/mm3
• Hemoglobin \>9 g/dL (in the absence of red blood cell transfusion)
• Adequate liver function, defined by:

You may not qualify if:

• Evidence of metastatic disease on bone scan and CT scan of chest/abdomen (or PET CT scan). Patients with intrathoracic metastatic adenopathy are eligible.
• Active infection or unexplained fever \>38.5°C during screening.
• Active infections including viral hepatitis and HIV.
• Active asthma or other condition requiring steroid therapy.
• Autoimmune disease including lupus erythematosus or rheumatoid arthritis. Topical or inhaled corticosteroids are allowed.
• 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.
• 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.
• 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.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as:
• 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
• uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
• 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.
• Any other investigational or anti-cancer treatments while participating in this study.
• Any other cancer

Sponsors & Collaborators

• Baylor Research Institute: lead

Study Sites (1)

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Dr. Joyce O'Shaughnessy
• Organization: Baylor Scott and White Health

joyce.oshaughnessy@usoncology.com

214-818-8472

Study Officials

• Joyce O'Shaughnessy, MD

  Baylor Health Care System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2013
• First Posted: December 23, 2013
• Study Start: May 1, 2014
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: October 11, 2021
• Results First Posted: March 13, 2020

Record last verified: 2021-10

Locations

US (1)