Entinostat, Lapatinib Ditosylate and Trastuzumab in Treating Patients With Locally Recurrent or Distant Relapsed Metastatic Breast Cancer Previously Treated With Trastuzumab Only

NCT01434303 | Completed Phase 1 DMC

• 8 other identifiers: NCI-2011-03222NCI 88712010-0842CDR00007108918871P30CA016672U01CA062461UM1CA186688
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of entinostat when given together with lapatinib ditosylate and trastuzumab in treating patients with breast cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes or has recurred (come back) at or near the same place as the original (primary) tumor, usually after a period of time during which the cancer could not be detected. Entinostat and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving entinostat together with lapatinib ditosylate and trastuzumab may kill more tumor cells.

Conditions

HER2/Neu Positive; Invasive Breast Carcinoma; Recurrent Breast Carcinoma; Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• RP2D for entinostat in combination with lapatinib ditosylate defined as the highest dose level in which 6 patients have been treated with at most 1 patient experiencing dose limiting toxicity

  Up to 28 days

Secondary Outcomes (1)

• Incidence of grade III or IV toxicities, graded according to Common Terminology Criteria for Adverse Events version 4

  Up to 28 days

Other Outcomes (4)

• Changes in CTCs levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab

  Baseline up to 28 days after completion of study treatment

• Changes in phosphorylated Akt levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab.

  Baseline up to 28 days after completion of study treatment

• Changes in phosphorylated HER2 levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab

  Baseline up to 28 days after completion of study treatment

Study Arms (1)

Treatment (entinostat, lapatinib ditosylate and trastuzumab)

EXPERIMENTAL

Patients receive entinostat 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. Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.

Drug: Entinostat; Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate; Biological: Trastuzumab

Interventions

Entinostat DRUG

Given PO

Also known as: HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275

Treatment (entinostat, lapatinib ditosylate and trastuzumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (entinostat, lapatinib ditosylate and trastuzumab)

Lapatinib Ditosylate DRUG

Given PO

Also known as: Tykerb

Treatment (entinostat, lapatinib ditosylate and trastuzumab)

Trastuzumab BIOLOGICAL

Given IV

Also known as: ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab-dkst

Treatment (entinostat, lapatinib ditosylate and trastuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients have histological confirmation of invasive breast carcinoma
• Patients have locally recurrent or distant relapsed metastatic disease
• Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (\> 2.0 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 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 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
• Both men and women and members of all races and ethnic groups are eligible for this trial

You may not qualify if:

• 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 metastasis \[mets\])
• Absolute neutrophil count (ANC) \< 1.5
• Hemoglobin =\< 9
• Platelet =\< 140,000
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

entinostat; Lapatinib; Trastuzumab; PF-05280014; Ogivri; trastuzumab biosimilar HLX02

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Naoto T Ueno

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2011
• First Posted: September 14, 2011
• Study Start: January 10, 2012
• Primary Completion: February 16, 2016
• Study Completion: February 16, 2016
• Last Updated: May 20, 2019

Record last verified: 2019-05

Locations

US (1)