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

NCT02120469 | Completed Phase 1 Results DMC

• 2 other identifiers: 14036NCI-2014-00844
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/IB trial studies the side effects and best dose of eribulin mesylate and everolimus in treating patients with breast cancer that does not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 protein (triple-negative) and has spread to other places in the body (metastatic). Eribulin mesylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor-negative; Stage IV Breast Cancer; Triple-negative Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing a Dose Limiting Toxicity (DLT) (Phase I) and the Recommended Phase IB Dose (RP2D)

  DLT defined as an adverse event (AE) or abnormal laboratory value as at least possibly related to the study medication and meets any of the criteria per NCI CTCAE v4.0.

  First cycle on treatment, up to 21 days

• Number of Subjects With Disease Progression Using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Phase IB)

  Progression determined using response evaluation criteria in solid tumors (RECIST) version 1.1 or showed clinical progression. RECIST criteria for progression includes: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Rates and associated 95% confidence limits will be estimated.

  Up to 2 years

Secondary Outcomes (4)

• Number of Participants With Grade 3 or Higher Toxicities (Phase IB)

  On treatment, 21 days per cycle up to 2 years

• Best Response Using the RECIST (Phase IB)

  Up to 2 years

• Median Overall Survival (Phase IB)

  From start of treatment to death due to any cause, assessed up to 2 years

• Median Progression Free Survival (Phase IB)

  Form the date treatment begins until the first date on which recurrence, progression, or death due to any cause, assessed up to 2 years

Study Arms (1)

Treatment (everolimus, eribulin mesylate)

EXPERIMENTAL

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; Drug: eribulin mesylate; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

everolimus DRUG

Given PO

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Treatment (everolimus, eribulin mesylate)

eribulin mesylate DRUG

Given IV

Also known as: B1939, E7389, ER-086526, halichrondrin B analog

Treatment (everolimus, eribulin mesylate)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (everolimus, eribulin mesylate)

laboratory biomarker analysis OTHER

Optional correlative studies

Treatment (everolimus, eribulin mesylate)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically-confirmed stage IV TNBC (patients who had metastatic disease within 6 months of lumpectomy or mastectomy for treatment of TNBC may be excused from repeat biopsy)
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly obtained samples cannot be provide (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the study principle investigator (PI)
• Patients must have had prior treatment with anthracyclines and/or taxanes (resistant) or platinum including adjuvant or neoadjuvant therapy
• Both measurable as well as non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, will be allowed
• Patients with chemotherapy for metastatic disease (patients with 0-3 prior lines of chemotherapy for metastatic breast cancer \[MBC\])
• Life expectancy of \>= 3 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
• Creatinine =\< 1.5 times the upper limit of normal (ULN)
• Total bilirubin less =\< to 1 times ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< to 2.5 times the ULN if no liver metastases; for patients with known liver metastases, AST and ALT must be =\< to 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 up to 8 weeks after ending treatment; 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

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered \> 3 weeks prior to entering the study
• Patients may not be receiving any other investigational agents
• Patients with symptomatic brain metastases are excluded from this clinical trial
• 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 strong or moderate cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/P-glycoprotein (PgP) inhibitors and CYP3A4/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 ending treatment; 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Rancho Cucamonga

Rancho Cucamonga, California, 91730, United States

Location

South Pasadena Cancer Center

South Pasadena, California, 91030, United States

Location

Related Publications (1)

• Lee JS, Yost SE, Blanchard S, Schmolze D, Yin HH, Pillai R, Robinson K, Tang A, Martinez N, Portnow J, Wen W, Yim JH, Brauer HA, Ren Y, Luu T, Mortimer J, Yuan Y. Phase I clinical trial of the combination of eribulin and everolimus in patients with metastatic triple-negative breast cancer. Breast Cancer Res. 2019 Nov 8;21(1):119. doi: 10.1186/s13058-019-1202-4.

  PMID: 31703728 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Everolimus; eribulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Yuan Yuan
• Organization: City of Hope

yuyuan@coh.org

626-359-8111

Study Officials

• Yuan Yuan, MD, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 18, 2014
• First Posted: April 22, 2014
• Study Start: October 1, 2014
• Primary Completion: March 20, 2019
• Study Completion: March 3, 2020
• Last Updated: July 5, 2022
• Results First Posted: April 25, 2022

Record last verified: 2022-06

Locations

US (3)