Trial Title:
Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer
NCT ID:
NCT05539365
Condition:
Anatomic Stage III Breast Cancer AJCC v8
Anatomic Stage IV Breast Cancer AJCC v8
Metastatic Triple-Negative Breast Carcinoma
Unresectable Triple-Negative Breast Carcinoma
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Alpha-type-1 Polarized Dendritic Cells
Description:
Given IT
Arm group label:
Treatment (ST-alpha-DC1, pembrolizumab)
Other name:
alphaDC1
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (ST-alpha-DC1, pembrolizumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (ST-alpha-DC1, pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo leukapheresis
Arm group label:
Treatment (ST-alpha-DC1, pembrolizumab)
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (ST-alpha-DC1, pembrolizumab)
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
SCH 900475
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Treatment (ST-alpha-DC1, pembrolizumab)
Other name:
Quality of Life Assessment
Summary:
This phase II trial tests the safety, side effects, and whether dendritic cell-based
treatment and pembrolizumab work in treating patients with triple negative breast cancer
that has spread to other places in the body (metastatic) or cannot be removed by surgery
(unresectable). The term triple-negative breast cancer refers to the fact that the cancer
cells don't have estrogen or progesterone receptors (ER or PR) and also don't make any or
too much of the protein called HER2 (the cells test "negative" on all 3 tests). Dendritic
cell-based treatment works by boosting the immune system (a system in our bodies that
protects us against infection) to recognize and destroy the cancer cells. Pembrolizumab,
is an immune checkpoint inhibitor drug, that works by targeting molecules that act as a
check and balance system for immune responses. Immune checkpoint inhibitor drugs are
designed to either "unleash" or "enhance" the cancer immune responses that already exist
by either blocking inhibitory molecules or by activating stimulatory molecules. Giving
dendritic cell-based therapy and pembrolizumab may decrease symptoms and improve quality
of life in patients with triple negative breast cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the clinical efficacy and safety and tolerability of a combination of
intratumorally injected autologous dendritic cells (DCs) and pembrolizumab in PD-L1
negative treatment-naive and refractory metastatic triple negative breast cancer
patients.
SECONDARY OBJECTIVES:
I. To assess progression-free survival and overall survival in metastatic triple negative
breast cancer patients that received the combination of intratumorally injected
autologous DCs and pembrolizumab.
II. To assess the clinical efficacy in the non-injected target lesion (optional biopsies
for this lesion).
OUTLINE:
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1
intratumorally (IT) on days 1, 8, and 50 in the absence of disease progression or
unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) on days 8,
29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients
who are receiving clinical benefit from treatment at the end of day 85, may continue to
receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo
tumor biopsies on days 1, 8, and 50 and computed tomography (CT) scans at baseline and
days 50 and 85.
After completion of study treatment, patients are followed up at 30 and 90 days after the
last dose of study drug, and then every 3 months for up to 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >= 18 years of age
- Pathologically confirmed diagnosis of unresectable or metastatic triple negative
breast cancer (TNBC) with no curative treatment options
- At least 2 target lesions present per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 at least one of which is amenable to biopsy and injection
- PD-L1 negative metastatic TNBC patients who are treatment naive in the first linen
metastatic setting are eligible
- Both PD-L1 positive and PD-L1 negative metastatic TNBC patients in the second line
setting and beyond are eligible
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2
- Platelets >= 75,000/uL
- Hemoglobin >= 8 g/dL
- Absolute Neutrophil Count (ANC) >= 1500/uL
- Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 30 mL/min
for participant with creatinine levels >1.5 x institutional ULN
- Total bilirubin: =< 2 x ULN OR direct bilirubin =< ULN for participants with total
bilirubin levels > 2 x ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT] =<
3 x institutional ULN (=< 5 x ULN for participants with liver metastases)
- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to
study entry. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately
- Participant must understand the investigational nature of this study and sign an
Independent Ethics Committee/Institutional Review Board approved written informed
consent form prior to receiving any study related procedure
Exclusion Criteria:
- Participants currently treated with systemic immunosuppressive agents, including
steroids (> than equivalent of 10 mg daily of prednisone) are ineligible until 3
weeks after removal from immunosuppressive treatment
- Patients with active autoimmune disease or history of transplantation
- Cardiac risk factors including:
- Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial
infarction, or ischemia) within 3 months of signing consent
- Patients with a New York Heart Association classification of III or IV
- Pregnant or nursing female participants
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they are radiologically stable, i.e. without evidence of progression for at
least 4 weeks by repeat imaging (note that the repeat imaging should be performed
during study screening), clinically stable and without requirement of steroid
treatment for at least 14 days prior to first dose of study intervention
- Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (=<2 weeks of radiotherapy) to non-CNS disease
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its
excipients
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has active Human Immunodeficiency Virus (HIV) infection
- Note: HIV testing is required
- Has active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or
active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- Note: Testing for Hepatitis B and Hepatitis C is required
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit comp
- Unwilling or unable to follow protocol requirements
- Any condition which in the Investigator's opinion deems the participant an
unsuitable candidate to receive study drug
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Contact:
Last name:
Shipra Gandhi
Phone:
716-845-1486
Email:
Shipra.Gandhi@roswellpark.org
Investigator:
Last name:
Shipra Gandhi
Email:
Principal Investigator
Start date:
October 1, 2024
Completion date:
October 1, 2026
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05539365
