Overview

Dose Escalation Study of HBI-8000 in Combination With Paclitaxel and Trastuzumab in Women With Advanced or Metastatic HER2+ Breast Cancer

Status:
Withdrawn
Trial end date:
1969-12-31
Target enrollment:
0
Participant gender:
Female
Summary
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor (HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with advanced or metastatic HER2+ breast cancer.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
HUYA Bioscience International
Treatments:
Albumin-Bound Paclitaxel
Paclitaxel
Trastuzumab
Criteria
Inclusion Criteria:

1. Female subject, age ≥18 years at the time of signing informed consent

2. Histologically or cytologically confirmed adenocarcinoma of breast, HER2+ as
determined by FISH or IHC

3. Having received at least one prior systemic therapy with FDA approved agent(s) for
metastatic disease and have no curative option

4. Measureable disease as defined by RECIST 1.1

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

6. Laboratory parameters within 14 days prior to dosing:

- Absolute neutrophil count (ANC) ≥ 1.5 X 109/L independent of growth factor
support

- Hemoglobin (Hgb) ≥9 gm/dL independent of transfusion or growth factor support

- Platelets (plt) ≥ 100 x 109/L independent of transfusion or growth factor support

- AST and ALT ≤2.5 x Upper Limit of Normal (ULN); if hepatic metastasis is present,
≤2.5 x ULN

- Serum total bilirubin ≤ 1.5 x ULN; if with Gilbert's Syndrome, direct bilirubin
must be normal

- Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 60ml/min

- Serum albumin > 3.0 g/dL

- Prothrombin time (PT)/International normalized ratio (INR) ≤ 1.5, partial
thromboplastin time (PTT) within normal limits (WNL) of the institution

7. Negative serum pregnancy test in subjects with child-bearing potential; and commit to
abstinence or comply with medically proven contraception methods

8. Agree to abstain from breast feeding from the start of study treatment and >28 days
after the last dose of study drugs.

9. Understand and voluntarily sign informed consent

Exclusion Criteria:

1. Receiving chemotherapy, immunotherapy, biological, radiation therapy or
investigational agent (therapeutic or diagnostic) within 4 weeks prior to receipt of
study medication. Major surgery, other than diagnostic surgery, within 4 weeks before
first study drug administration.

2. Significant cardiac history:

- History of myocardial infarction or ischemic heart disease within 1 year before
the first study drug administration

- Uncontrolled arrhythmia, such as ventricular tachycardia, ventricular
fibrillation; second- or third-degree heart block; unstable angina, coronary
angioplasty or stenting, or myocardial infarction (MI) within 6 months of study
entry

- History of congenital QT prolongation, or baseline QTcF > 470 ms using
Fridericia's formula

- ECG findings consistent with active ischemic heart disease

- New York Heart Association Class III or IV cardiac disease

- Left ventricular Ejection Fraction measuring ≥ 55% at baseline ECHO

- Uncontrolled hypertension: blood pressure consistently greater than 150 mm Hg
systolic and 100 mm Hg diastolic in spite of antihypertensive medication

3. Patients with active brain metastasis or leptomeningeal involvement. Patients who have
brain metastases that have been previously treated, who are asymptomatic, and whose
lesions by imaging are at least stable and without interim development of new lesions
for at least 6 weeks may be enrolled. Patients who require continued steroid therapy
as management for their brain metastases are not eligible

4. Persistent diarrhea or malabsorption NCI CTCAE (version 4.03) grade ≥ 1 despite
medical management, ulcerative colitis, inflammatory bowel disease, resection of the
stomach or small bowel, or other disease or condition significantly affecting GI
function

5. Peripheral neuropathy NCI CTCAE (Version 4.03) Grade ≥ 2

6. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.

7. Known infection with human immunodeficiency virus (HIV) or active hepatitis A, B, or
C.

8. Patients with a prior hypersensitivity reaction to any product containing
polyvinylpyrrolidone, microcrystalline cellulose, lactose monohydrate, sodium starch
glycolate, talc or magnesium stearate.

9. Second malignancy unless in remission for > 5 years. (Non-melanoma skin cancer or
carcinoma in situ of the cervix treated with curative intent is not exclusionary.)

10. Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient. Examples of such conditions include infection requiring
parenteral anti-infective treatment, hydronephrosis, liver failure, any altered mental
status or any psychiatric condition that would interfere with the understanding of the
informed consent.

11. Unwilling or unable to comply with procedures required in this protocol.