Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT02120469
First received: April 18, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

This phase I trial studies the side effects and best dose of eribulin mesylate and everolimus in treating patients with triple-negative metastatic breast cancer. Eribulin mesylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving eribulin mesylate together with everolimus may be a safe and successful treatment for patients with triple-negative metastatic breast cancer.


Condition Intervention Phase
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Triple-negative Breast Cancer
Drug: everolimus
Drug: eribulin mesylate
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IB Trial of Eribulin and Everolimus in Patients With Triple Negative Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • R2PD of the eribulin mesylate and everolimus, determined according to the NCI CTCAE v4.0 (Phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Tables will be created to summarize all toxicities and side effects by dose, course, organ and severity. Rates and associated 95% confidence limits will be estimated for dose-limiting toxicities at the R2PD.

  • Event-free survival using the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase IB) [ Time Frame: At 4 months ] [ Designated as safety issue: No ]
    Rates and associated 95% confidence limits will be estimated. Kaplan Meier methods will be used to estimate the median and 95% confidence limits. Descriptive statistics will be provided for the patient demographics.


Secondary Outcome Measures:
  • Incidence of adverse events, graded according to the NCI CTCAE v4.0 (Phase IB) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Tables will be created to summarize all toxicities and side effects by dose, course, organ and severity. Rates and associated 95% confidence limits will be estimated.

  • Response rate using the RECIST (Phase IB) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Rates and associated 95% confidence limits will be estimated.

  • Overall survival (Phase IB) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Kaplan Meier methods will be used to estimate the median and 95% confidence limits. Descriptive statistics will be provided for the patient demographics.


Other Outcome Measures:
  • PK parameters of everolimus in blood samples [ Time Frame: Baseline, 1, 2, 4, 6, and 24 hours on day 1 of course 1 and 2 ] [ Designated as safety issue: No ]
    Non-compartmental PK analyses of everolimus will be performed using statistical moment theory and according to the rule of linear trapezoids and statistical moment theory.

  • PK parameters of eribulin mesylate in plasma samples [ Time Frame: Baseline, 5, 10, 15, and 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 167 hours on day 1 of course 2 ] [ Designated as safety issue: No ]
    Compartmental analyses will be performed for eribulin data. Secondary pharmacokinetic parameters (e.g. CLsys, Volume of distribution [Vd], half-life [t1/2's], and area under the curve [AUC 0->infinity) will be determined for each individual and a two-stage approach will be used to describe the study population pharmacokinetics. Population means and standard deviations will be compared to values obtained from patients treated on trials of single agent eribulin mesylate.


Estimated Enrollment: 45
Study Start Date: October 2014
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (everolimus, eribulin mesylate)
Patients receive everolimus PO QD on days 1-21 and eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: everolimus
Given PO
Other Names:
  • 42-O-(2-hydroxy)ethyl rapamycin
  • Afinitor
  • RAD001
Drug: eribulin mesylate
Given IV
Other Names:
  • B1939
  • E7389
  • ER-086526
  • halichrondrin B analog
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of everolimus and eribulin (eribulin mesylate), and determine the recommended Phase IB dose (RP2D) of the drug combination in patients with resistant metastatic triple negative breast cancer (TNBC). (Phase I) II. To evaluate the event-free survival (EFS) rate for patients with resistant metastatic TNBC at the RP2D of everolimus and eribulin to determine if the drug combination is worthy of further study. (Phase IB)

SECONDARY OBJECTIVES:

I. To determine response rate in patients with resistant metastatic TNBC. (Phase IB) II. To determine overall survival (OS) in patients with resistant metastatic TNBC. (Phase IB) III. To determine toxicity in patients with resistant metastatic TNBC. (Phase IB) IV. To determine pharmacokinetics (PK) for everolimus and eribulin in patients with resistant metastatic TNBC. (Phase IB) V. To collect blood, skin punch biopsies, and tumor biopsies before and after treatment from all patients and perform proteomic analysis to determine the level of inhibition of the phosphatidylinositol 3 kinase (PI3K) pathway in tumor cells versus non-therapeutic targets. (Phase IB)

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

Patients receive everolimus orally (PO) once daily (QD) on days 1-21 and eribulin mesylate intravenously (IV) on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically-confirmed stage IV adenocarcinoma TNBC
  • Patients who progressed on anthracyclines and/or taxanes (resistant)
  • Patients with measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan
  • Previous chemotherapy for metastatic disease (up to =< 3 prior lines of chemotherapy for MBC); this includes prior everolimus therapy
  • Prior radiation therapy
  • Life expectancy of > 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Hemoglobin >= 9.0 g/dl
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.0 times upper limit of normal limit (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 times the ULN
  • Creatinine =< 1.5 times the ULN
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered > 4 weeks prior to entering the study
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases are excluded from this trial; patients with neurological symptoms must undergo a CT scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
  • Uncontrolled current illness including, but not limited to, ongoing or active infection (> grade 2 based on the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]4.0, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women
  • Prior eribulin use
  • Patients with human immunodeficiency virus (HIV), chronic hepatitis B, or chronic hepatitis C (known from the existing medical record)
  • Concomitant use with cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/P-glycoprotein (PgP) inducers
  • Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after; highly effective contraception methods include combination of any two of the following:

    • Use of oral, injected or implanted hormonal methods of contraception or
    • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
    • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
    • Total abstinence
    • Male/female sterilization

      • Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
  • Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02120469

Locations
United States, California
City of Hope Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Thehang H. Luu    800-826-4673    TLuu@coh.org   
Principal Investigator: Thehang H. Luu         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Thehang Luu City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT02120469     History of Changes
Other Study ID Numbers: 14036, NCI-2014-00844, 14036
Study First Received: April 18, 2014
Last Updated: April 18, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on October 01, 2014