BridgeMD
New treatment option for Anatomic Stage IV Breast Cancer AJCC v8
Official title Dendritic Cell Vaccines Against Her2/Her3 and Pembrolizumab for the Treatment of Brain Metastasis From Triple Negative Breast Cancer or HER2+ Breast Cancer
ClinicalTrials.gov ID: NCT04348747
What this study is testing
What is Anti-HER2/HER3 Dendritic Cell Vaccine?
Anti-HER2/HER3 Dendritic Cell Vaccine is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for anatomic stage iv breast cancer ajcc v8.
Also referred to as Anti-HER2/3 DC Vaccine, Anti-HER2/3 Dendritic Cell Vaccine.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase IIa trial studies how well dendritic cell vaccines against Her2/Her3 and pembrolizumab work for the treatment of triple negative breast cancer or HER2+ breast cancer or HER+ Breast cancer that has spread to the brain (brain metastasis). Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the cancer cells.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older, women only
You may be able to join if
- female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
- A WOCBP who agrees to follow contraceptive guidance
- WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected...
- Negative serum and highly sensitive urine pregnancy test(s):
You likely can't join if
- Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration...
- Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs
- May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an...
- Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives...
- Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or...
See the full eligibility criteria
Who can join
- female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
- A WOCBP who agrees to follow contraceptive guidance
- WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods...
- Negative serum and highly sensitive urine pregnancy test(s):
- At initial screening prior to eligibility confirmation
- within 72 hours prior to leukapheresis if \>72 hours have passed between screening test and the Leukapheresis visit
- Pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab (Initial Treatment Phase);
- at the End of Treatment (EOT) Assessment; and
- whenever pregnancy is otherwise suspected. Note: In the event that 72 hours have elapsed between the screening pregnancy test and leukapheresis, another pregnancy test must be performed and must be negative in order for...
- Histologically or cytologically confirmed diagnosis of triple negative breast cancer (TNBC) (estrogen receptor [ER] =\< 1%, progesterone receptor [PR] =\< 1% HER2 negative) or HR+ breast cancer
- HER2 testing should be performed on the invasive component using a validated immunohistochemistry (IHC) or in situ hybridization (ISH) assay
- IHC staining is defined as:
- IHC 3+ if there is complete and intense circumferential membrane staining within \> 10 percent of tumor cells. All IHC 3+ tumors are considered HER2 positive
- IHC 2+ if there is incomplete and/or weak/moderate, circumferential membrane staining within \> 10 percent of tumor cells. All IHC 2+ tumors are reported as HER2 equivocal
- IHC 1+ if there is faint or barely perceptible, incomplete membrane staining within \> 10 percent of tumor cells. All IHC 1+ tumors are reported as HER2 negative
- IHC 0 if (1) no staining is observed, or (2) there is faint or barely perceptible, incomplete membrane staining within \< 10 percent of tumor cells. All IHC 0 tumors are reported as HER2 negative
- Equivocal HER2 testing should trigger reflex HER2 testing using ISH on the same specimen or a new test (using a different specimen with either IHC or ISH)
- Results from ISH are defined as the ratio of gene amplification of HER2 and the chromosome 17 enumeration probe (CEP17). Results are reported as:
- ISH positive if the HER2/CEP17 ratio is \>= 2.0, and the HER2 copy number signals/cell is \>= 4
- Definitive diagnosis will be rendered pending further workup in the following instances:
- If the HER2/CEP17 ratio is \>= 2.0 and an average HER2 copy number is \< 4.0 signals/cell - negative if confirmed on retesting
- If the HER2/CEP17 ratio is \ = 6.0 signals/cell positive - if confirmed on retesting
- If the HER2/CEP17 ratio is \ = 4.0 and \< 6.0 signals/cell negative - if confirmed on retesting
- ISH negative if the HER2/CEP17 ratio is \< 2.0 and average HER2 copy number is \< 4.0 signals/cell
- Measurable brain disease as per RANO-BM criteria modified to include the cut off point of 0.5 cm or higher. Have at least one untreated (includes irradiation) brain metastasis approved by a research team that meets the...
- \>= 0.5 cm AND twice the magnetic resonance imaging (MRI) slice thickness; and
- \< 3.0 cm, that is asymptomatic and does not require local therapy at the time of enrollment (i.e. target lesion(s))
- Of note, lesions \>= 0.5 cm and \< 3 cm may be determined ineligible by the research team because of location or symptoms. An untreated brain metastasis is defined as a lesion not present at the time of whole brain...
- Any brain metastasis \>= 3.0 cm or causing symptoms must have previously been treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at...
- Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted \>=2 weeks prior to initial Dendritic Cell (DC) vaccine dose (leaving one or more lesions which are not radiated and will be used as target lesions)...
- Previous whole brain radiation is allowed if patient has been diagnosed with recurrent, progressive brain metastasis. Previously irradiated lesions would be considered non-target lesions
- Previously resected lesions or those treated with SRS would be considered nontarget lesions. There is no limitation on prior local therapies to other lesions.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Toxicity that has not recovered to \<=Grade 1 is allowed if it meets the inclusion requirments for lab parameters (Participants with \<= Grade 2 neuropathy may be eligible)
- Patients must have adequate organ and marrow function as defined below (specimens must be collected within 10 days prior to the start of study treatment):
- Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
- Leukocytes: \>= 3 x 10\^9/L
- Absolute neutrophil count: \>= 1.5 x 10\^9/L
- Platelets: \>= 100 x 10\^9/L
- Total bilirubin: =\ 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): =\< 2.5 x institutional upper limit of normal (=\< 5 x ULN...
- Creatinine OR Measured or calculated creatinine clearance (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 ×...
- International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (APTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic...
- No evidence of leptomeningeal disease
- If patient is on steroids, they must be on a steroid dose less than or = to an equivalent prednisone dose of 10 mg daily
- Life expectancy of \> 3 months
- Prior checkpoint inhibitors permitted 3 weeks prior to enrollment
- If the disease has progressed on current treatment in the CNS, prior to consent, patients may continue Her 2 directed antibody treatment (trastuzumab and pertuzumab); aromatase inhibitor or tamoxifen while on the study...
- Patients with systemic disease will be managed as detailed in Section 10.1 - Patients who develop systemic disease progression on the protocol will be managed as detailed in Section 10.4.2
What rules you out
- Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration of the study) or in the Investigator's opinion deems the participant...
- Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs
- May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of DC vaccine treatment
- Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives (whichever is sooner) prior to start of treatment (first DC vaccine) or...
- Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin...
- History of allogenic tissue/solid organ transplantation
- Has an active infection requiring systemic therapy which in the investigator's opinion will increase risk to the patient
- Has known active hepatitis B or hepatitis C infection (Testing is not mandatory)
- Has known immunosuppressive disease (e.g. human immunodeficiency virus [HIV], acquired immunodeficiency syndrome [AIDS] or other immune depressing disease). Testing is not mandatory
- Has received a blood transfusion in the two weeks prior to leukapheresis
- Pregnant or actively nursing (females who agree to stop nursing would be eligible) participants
- Unwilling or unable to follow protocol requirements
- Brain lesion size with significant midline shift or obstructive hydrocephalus
- The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed unless at a low dose, not to exceed 10 mg of prednisone (or equivalent) per day
- History of stroke or transient ischemic attack within 6 months prior to study enrollment
- History of (non-infectious) pneumonitis /interstitial lung disease that required steroids, or has current pneumonitis/ interstitial lung disease
- Presence of leptomeningeal disease
- Any contraindication to MRI (i.e., patients with pacemakers or other metal implanted medical devices). An MRI safety questionnaire is required prior to MR imaging
- Has received prior radiotherapy within 2 weeks of start of study treatment with dendritic cell (DC) vaccine and/or has received SRS \<2. weeks prior to the administration of the first DC vaccine dose. Participants must...
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., FluMist)...
- 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...
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma...
- A WOCBP who has a positive urine or blood pregnancy test at screening and within 72 hrs prior to leukapheresis \ Note: in the event that 72 hrs have elapsed between the initial screening pregnancy test and...
- Known active carcinomatous meningitis
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
The study team makes the final eligibility decision.
Where it's taking place
- Tampa, Florida, United States
- Buffalo, New York, United States
- Charlottesville, Virginia, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling female, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Tampa, Florida, United States; Buffalo, New York, United States; Charlottesville, Virginia, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.