Know Cancer

or
forgot password

Phase I/II Study of Entinostat and Lapatinib in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
HER2-positive Breast Cancer, Inflammatory Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

Phase I/II Study of Entinostat and Lapatinib in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed


PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (RP2D) for entinostat in combination with
lapatinib (lapatinib ditosylate) in patients who have received trastuzumab for human
epidermal growth factor receptor 2+ (HER2+) metastatic breast cancer.

II. To determine the tumor response to entinostat in combination with lapatinib in patients
who have received trastuzumab for HER2+ metastatic breast cancer in the non-inflammatory
breast cancer (IBC) cohort.

SECONDARY OBJECTIVES:

I. To determine the toxicity of combination therapy with entinostat and lapatinib in
patients who have received trastuzumab for HER2+ metastatic breast cancer.

II. To determine time to tumor progression, time to tumor response, and progression-free
survival (PFS) up to 2 years. (Phase II) III. To determine overall survival at 2 years in
patients who have received trastuzumab for HER2+ metastatic breast cancer.

IV. To determine the toxicity of combination therapy with entinostat and lapatinib in
patients who have received trastuzumab for HER2+ metastatic breast cancer.

EXPLORATORY OBJECTIVES:

I. Determine whether the 2-drug combination modulates the expression of HER2, phosphorylated
HER2 (pHER), epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), protein
kinase B (Akt), and phosphorylated Akt (pAkt) in breast tumors and/or circulating tumor
cells (CTCs).

OUTLINE: This is a phase I, dose-escalation study of entinostat followed by a phase II
study.

Patients receive entinostat orally (PO) on days 1 and 15, and lapatinib tosylate PO on days
1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity. Tumor tissue samples collected at diagnosis and blood samples collected at
baseline and after treatment are analyzed for pEGFR/EGFR, pHER2/HER2, and pAkt/Akt
expression.

After completion of study therapy, patients are followed up for 28 days or until toxicities
are resolved.


Inclusion Criteria:



- Patients have histological confirmation of invasive breast carcinoma

- Patients have locally recurrent or distant relapsed metastatic disease (Phase I
portion of the study-any metastatic breast cancer; Phase II portion of the study
including non-inflammatory breast cancer [IBC] only)

- Patients have positive HER2 expression by IHC (3+) or fluorescence in situ
hybridization (FISH) testing (> 2.2 ratio)

- Patients are able to swallow and retain oral medication (i.e., no uncontrolled
vomiting, inability to swallow, or diagnosis of chronic malabsorption)

- Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Patients must have received prior trastuzumab for > 2-month period before disease
recurrence or progression while on trastuzumab-based therapy

- Patients have ability and willingness to sign written informed consent

- Female patients of childbearing potential (a female not free from menses > 2 years or
not surgically sterilized) must be willing to use an adequate barrier method of
contraception to prevent pregnancy or agree to abstain from heterosexual activity
throughout the study; male patients who are able to father children must use an
adequate barrier method of contraception

- Female patients of childbearing potential must have negative serum pregnancy test
within 14 days of starting protocol therapy

- Patients with brain metastasis who have no signs of progressive disease 4 months
after the completion of brain metastasis treatment (radiation therapy, surgery, etc.)
do not require anticonvulsants or corticosteroids, and have been off such drugs for
at least 7 days, allowed

- Both men and women and members of all races and ethnic groups are eligible for this
trial

Exclusion Criteria:

- Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy,
biological therapy and hormonal therapy) while taking study medication

- Serum bilirubin >= 1.5 x upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >=3 x ULN (with
or without liver mets)

- Absolute neutrophil count (ANC) < 1.5

- Hemoglobin =< 9

- Platelet =< 75,000

- Patients have an active infection and require intravenous (IV) or oral antibiotics

- Cardiac arrhythmia requiring maintenance medication

- History of gastrointestinal disorders (medical disorders or extensive surgery) which
may interfere with the absorption of the study drug

- Patients have a concurrent disease or condition that would make them inappropriate
for study participation, or any serious medical disorder that would interfere with
patients' safety

- Serum creatinine > 2.0 mg/dL

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

RP2D for entinostat in combination with lapatinib ditosylate (Phase I)

Outcome Time Frame:

Up to 28 days

Safety Issue:

No

Principal Investigator

Naoto Ueno

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-03222

NCT ID:

NCT01434303

Start Date:

January 2012

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Inflammatory Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Inflammatory Breast Neoplasms

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030