Clinical Trial: NCT02479230 - My Cancer Genome

NCT02479230

Description:

This pilot clinical trial studies the safety of a dendritic cell vaccine when given with gemcitabine hydrochloride in treating patients with breast cancer that has spread beyond the breast and local lymph nodes to other organs in the body. The vaccine is made up of natural cells found in the blood, called dendritic cells, and peptides, or small fragments of protein which are loaded onto the dendritic cells. This combination may help activate the immune system against stromal cells, which are cells that help cancer cells survive in the body. Gemcitabine hydrochloride is a chemotherapy drug that is given before the vaccine to help shrink the tumor and control cells that may interfere with the activity of the vaccine. Interfering with the stromal cells that help support the growth of cancer cells may lead to the death of the cancer cells.

Related Conditions:

Breast Carcinoma

Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02479230

Trial Eligibility

Document

Title

Brief Title: Type I-Polarized Autologous Dendritic Cell Vaccine With Tumor Blood Vessel Antigen-Derived Peptides in Metastatic Breast Cancer Patients
Official Title: Pilot Trial of Type I-Polarized Autologous Dendritic Cell Vaccine Incorporating Tumor Blood Vessel Antigen-Derived Peptides in Patients With Metastatic Breast Cancer

Clinical Trial IDs

ORG STUDY ID: CASE3113
SECONDARY ID: NCI-2014-00265
NCT ID: NCT02479230

Conditions

Breast Cancer
Metastatic Breast Cancer

Interventions

Drug	Synonyms	Arms
tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell vaccine	αDC1-TBVA vaccine	vaccine: gemcitabine hydrochloride
gemcitabine hydrochloride	1-(2-oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,, 2-difluororibose hydrochloride,, 103882-84-4, 2'-deoxy-2',, 2'-difluorocytidine hydrochloride,, 2'deoxy-2',, 47762,, 613327,, dFdC,, dFdCyd,, difluorodeoxycytidine hydrochloride,, gemcitabine,, Gemzar,, LY-188011	vaccine: gemcitabine hydrochloride

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess the safety of gemcitabine hydrochloride (GEM) + alpha-type-1 dendritic cell
      (αDC1)-tumor blood vessel antigen (TBVA) vaccination (tumor blood vessel antigen
      peptide-pulsed alpha-type-1 polarized dendritic cell vaccine).

      II. Assess the clinical response of metastatic breast cancer (MBC) to GEM + αDC1-TBVA
      vaccination.

      III. Determine the clinical efficacy of GEM + αDC1-TBVA vaccination in generating T-helper 1
      cell (Tc1) immunity.

      IV. Correlate changes in myeloid-derived suppressor cells (MDSC) and regulatory T cells
      (Tregs) with the generation of anti-TBVA T-cell immunity.

      OUTLINE:

      Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and
      8. Treatment repeats every 21 days for 3 courses. Beginning 3, 7, or 10 days later, patients
      receive tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell
      vaccine intradermally (ID) followed by a second vaccination 7 days later. Courses may repeat
      after at least 4 weeks in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days.

Trial Arms

Name	Type	Description	Interventions
vaccine: gemcitabine hydrochloride	Experimental	Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 3 courses. Beginning 3, 7, or 10 days later, patients receive tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell vaccine ID followed by a second vaccination 7 days later. Courses may repeat after at least 4 weeks in the absence of disease progression or unacceptable toxicity.	tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell vaccine gemcitabine hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be human leukocyte antigen (HLA)-A2+

          -  Histologically confirmed breast cancer

          -  Patients must have evidence of metastatic disease measurable by Response Evaluation
             Criteria in Solid Tumors (RECIST) criteria or non-measurable lytic or mixed (lytic +
             blastic) bone lesions in the absence of measurable disease; Note: Measurable lesions
             include lytic or mixed (lytic + blastic) bone lesions, with an identifiable 10 mm soft
             tissue component that meets the measurability criteria per RECIST

          -  There is no limit to the number of prior systemic treatment regimens

          -  Patients must have a life expectancy of > 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Prior GEM therapy is acceptable as long as the last dose was ≥ 3 months from
             registration on this study

          -  Patients may have treated and stable brain metastases; they must be off steroids and
             must have had stable brain metastases for at least 6 months

          -  White blood cell (WBC) > 3.0 x 10^9/L

          -  Platelets > 100 x 10^9/L

          -  Hemoglobin (Hgb) ≥ 10.0 gm/dl

          -  Creatinine < 1.5 mg/dl

          -  Bilirubin (total) < 2.0 ml/dl

          -  Aspartate aminotransferase (AST) < 5.0 x normal institutional limits

          -  Alkaline phosphatase < 2.5 upper limit of normal (ULN) (< 10 x ULN in presence of bone
             metastases)

          -  Serum calcium ≤ 12 mg/dl

          -  International normalized ratio (INR) < 1.5, except for subjects receiving warfarin
             therapy; for subjects who are receiving warfarin for prophylaxis or treatment of
             thrombosis, INR values should be carefully monitored while patients are on study

          -  All patients must be informed of the investigational nature of this study and must
             provide written informed consent in accordance with institutional and federal
             guidelines; a copy of the informed consent document signed by the patient must be
             given to the patient

          -  Patients must have a negative pregnancy test by urinalysis

          -  Use of an effective means of contraception (men and women) is mandated in subjects of
             child-bearing potential; female subjects will be advised that they not become pregnant
             for at least one month after completing participation in the study; avoiding sexual
             activity is the only certain method to prevent pregnancy; however, if subjects choose
             to be sexually active, they should use an appropriate "double barrier" method of birth
             control (such as female use of a diaphragm, intrauterine device [IUD], or
             contraceptive sponge, in addition to male use of a condom) or the use of prescribed
             "birth control" pills, injections, or implants

        Exclusion Criteria:

          -  HLA-A2 negative patients

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness

          -  Presence of bleeding diathesis

          -  Current treatment on another clinical trial

          -  Patients with organ allografts

          -  Pregnancy or breast-feeding; female patients must be surgically sterile or be
             post-menopausal, or must agree to use effective contraception during the period of
             therapy; all female patients with reproductive potential must have a negative
             pregnancy test (serum or urine) prior to enrollment; male patients must be surgically
             sterile or must agree to use effective contraception during the period of therapy; the
             definition of effective contraception will be based on the judgment of the principal
             investigator or a designated associate

          -  Other severe acute or chronic medical or psychiatric conditions, or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Number of toxicities
Time Frame:	30 days after completion of study
Safety Issue:
Description:	Incidence of toxicities, evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Secondary Outcome Measures

Measure:	mean change in Type-1 immune function
Time Frame:	24 weeks after treatment
Safety Issue:
Description:	Average immune response as measured by the interferon gamma [IFN-γ] cluster of differentiation (CD)8+ T cell (Tc1) response to the vaccine-associated TBVA peptides.

Measure:	Number of patients with clinical response
Time Frame:	Up to 30 days after study is complete
Safety Issue:
Description:	Clinical response as assessed using RECIST criteria.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	Joseph Baar, MD, PhD

Trial Keywords

vaccine
breast cancer
metastatic

Last Updated

May 11, 2020

Clinical Trials /

Type I-Polarized Autologous Dendritic Cell Vaccine With Tumor Blood Vessel Antigen-Derived Peptides in Metastatic Breast Cancer Patients