Overview

Ivermectin and Pembrolizumab for the Treatment of Metastatic Triple Negative Breast Cancer

Status:
Not yet recruiting
Trial end date:
2024-05-08
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies the side effects and best dose of ivermectin in combination with pembrolizumab and to see how well they they work in shrinking tumors in patients with triple negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivermectin may help block the formation of growths that may become cancer. Giving ivermectin with pembrolizumab may increase the effect of pembrolizumab in shrinking tumors in patients with triple negative breast cancer.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
City of Hope Medical Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Ivermectin
Pembrolizumab
Criteria
Inclusion Criteria:

- Documented informed consent of the participant and/or legally authorized
representative

- Assent, when appropriate, will be obtained per institutional guidelines

- Agreement to research biopsies on study and once during study, exceptions may be
granted with study principal investigator (PI) approval. End of study biopsy is
optional

- Age: >= 18 years

- Eastern Cooperative Oncology Group (ECOG) =< 1

- Life expectancy >= 3 months

- Ability to read and understand English, Mandarin, Armenian or Spanish for
questionnaires

- Histologically confirmed metastatic triple negative breast cancer. Triple negative
status will be defined as estrogen receptor (ER) and progesterone receptor (PR) =< 10%
and HER2 negative (by immunohistochemistry [IHC] or fluorescence in situ hybridization
[FISH]), per American Society of Clinical Oncology (ASCO)/College of American
Pathologists (CAP) guidelines

- Patients must have progressed on (or intolerant of or ineligible for) 1, no more than
2 prior lines of chemotherapy and/or immune checkpoint inhibitor for
advanced/metastatic disease

- Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1. Lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions

- Fully recovered from the acute toxic effects (except alopecia) to =< grade 2 from
prior anti-cancer therapy

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L. Criteria must be met without erythropoietin
dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks

- Total serum bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN
for participants with total bilirubin levels > 1.5 x ULN

- Aspartate aminotransferase (AST) =< 1.5 x ULN or =< 3 x ULN with liver metastases

- Alanine aminotransferase (ALT) =< 1.5 x ULN or =< 3 x ULN with liver metastases

- Creatinine =< 1.5 x ULN OR calculated creatinine clearance >= 30 mL/min for
participant with creatinine levels >1.5 x institutional ULN

- 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 range of intended use of
anticoagulants

- Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram

- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required

- A male participant must agree to use a contraception during the treatment period and
for at least 90 days after the last dose of study treatment and refrain from donating
sperm during this period

- A 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) OR

- Females of child-bearing potential must be willing to use effective contraception
during study and for 30 days after the last dose

Exclusion Criteria:

- 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

- Chemotherapy, radiation therapy, biological therapy, immunotherapy within 28 days
prior to day 1 of protocol therapy

- Participants must not have received 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-central
nervous system (CNS) disease

- Other investigational products. Participants may not be currently participating in or
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

- Participants on any dose of warfarin. Use of low molecular weight heparin,
antithrombin agents, anti-platelet agents or factor Xa inhibitors is allowed

- Herbal medications (cannabidiol [CBD] allowed)

- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed

- Issues with tolerating oral medication (e.g., inability to swallow pills,
malabsorption issues, ongoing nausea or vomiting during screening)

- Women who are or are planning to become pregnant or breastfeed

- Known allergy to any of the components within the study agents and/or their excipients

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for at least three years

- Participants must not have known active 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

- Intercurrent or historic medical condition that increases subject risk in the opinion
of the Investigator. Eligibility may be revisited for intercurrent medical conditions
once resolution/recovery is deemed adequate by the investigator (e.g., recovery from
major surgery, completion of treatment for severe infection).

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA]
[qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C
is required unless mandated by local health authority

- Has a known history of active TB (Mycobacterium tuberculosis)

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment

- Has had an allogenic tissue/solid organ transplant

- Significant cardiovascular impairment: history of congestive heart failure greater
than New York Heart Association (NYHA) class II, unstable angina, myocardial
infarction, or stroke within 6 months of the first dose of study drug, or cardiac
arrhythmia requiring medical treatment at screening

- Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine
collection for quantitative assessment indicates that the urine protein is < 1 g/24
hours

- Has 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, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and is allowed

- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures

- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)