Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01434303
Other study ID # NCI-2011-03222
Secondary ID NCI-2011-03222NC
Status Completed
Phase Phase 1
First received
Last updated
Start date January 10, 2012
Est. completion date February 16, 2016

Study information

Verified date May 2019
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

PRIMARY OBJECTIVES:

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

II. To determine the maximum tolerated dose (MTD) for entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).

SECONDARY OBJECTIVES:

I. To determine the toxicity of combination therapy with entinostat and lapatinib in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I).

II. To determine the toxicity of entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).

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), v-akt murine thymoma viral oncogene homolog 1 (Akt), and phosphorylated Akt (pAkt) in breast tumors and/or circulating tumor cells (CTCs).

OUTLINE: This is a dose-escalation study of entinostat.

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. Patients in the Phase I trastuzumab cohort also receive maintenance dose of trastuzumab intravenously (IV) over 30-90 minutes every 3 weeks.

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


Recruitment information / eligibility

Status Completed
Enrollment 37
Est. completion date February 16, 2016
Est. primary completion date February 16, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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

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 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Entinostat
Given PO
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Lapatinib Ditosylate
Given PO
Biological:
Trastuzumab
Given IV

Locations

Country Name City State
United States M D Anderson Cancer Center Houston Texas

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Changes in CTCs levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no). Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test. If the data is skewed, Wilcoxon rank-sum test will be used. Baseline up to 28 days after completion of study treatment
Other Changes in phosphorylated Akt levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab. Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no). Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test. If the data is skewed, Wilcoxon rank-sum test will be used. Baseline up to 28 days after completion of study treatment
Other Changes in phosphorylated HER2 levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no). Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test. If the data is skewed, Wilcoxon rank-sum test will be used. Baseline up to 28 days after completion of study treatment
Other Changes in phosphorylated EGFR levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no). Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test. If the data is skewed, Wilcoxon rank-sum test will be used. Baseline up to 28 days after completion of study treatment
Primary 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 Incidence of grade III or IV toxicities, graded according to Common Terminology Criteria for Adverse Events version 4 Up to 28 days
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04052555 - Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer Phase 1
Recruiting NCT04521764 - A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer Phase 1
Completed NCT00100750 - Tipifarnib and Gemcitabine Hydrochloride in Treating Women With Metastatic Breast Cancer Phase 1/Phase 2
Suspended NCT03737695 - Clinical Information and Biospecimen Collection From Patients With Recurrent or Stage IV Breast Cancer
Active, not recruiting NCT02595905 - Cisplatin With or Without Veliparib in Treating Patients With Recurrent or Metastatic Triple-Negative and/or BRCA Mutation-Associated Breast Cancer With or Without Brain Metastases Phase 2
Terminated NCT02149173 - F-18 FES PET/CT in Measuring Hormone Expression in Patients With Primary, Recurrent, or Metastatic Breast Cancer Undergoing Endocrine-Targeted Therapy N/A
Completed NCT00390455 - Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive Phase 3
Recruiting NCT03213041 - Pembrolizumab and Carboplatin in Treating Patients With Circulating Tumor Cells Positive Metastatic Breast Cancer Phase 2
Not yet recruiting NCT04529044 - 177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer Phase 2
Completed NCT00699491 - Cixutumumab and Temsirolimus in Treating Patients With Locally Recurrent or Metastatic Breast Cancer Phase 1/Phase 2
Completed NCT03364348 - 4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer Phase 1
Terminated NCT01149356 - RO4929097 And Exemestane in Treating Pre- and Postmenopausal Patients With Advanced or Metastatic Breast Cancer Phase 1
Completed NCT01964924 - Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer Phase 2
Completed NCT00785291 - Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer Phase 3
Terminated NCT02370264 - Questionnaires in Identifying Upper Extremity Function and Quality of Life After Treatment in Patients With Breast Cancer N/A
Terminated NCT01071564 - RO4929097 and Vismodegib in Treating Patients With Breast Cancer That is Metastatic or Cannot Be Removed By Surgery Phase 1
Terminated NCT00998738 - Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer Phase 3
Active, not recruiting NCT00520975 - First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU Phase 3
Completed NCT01251874 - Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer Phase 1
Active, not recruiting NCT03281902 - Genetic Analysis in Blood and Tumor Samples From Patients With Advanced or Metastatic Estrogen Receptor Positive and HER2 Negative Breast Cancer Receiving Palbociclib and Endocrine Therapy