Phase 2 Study - Aurora + Angiogenic Kinase Inhibitor ENMD-2076 in Previously Treated Locally Advanced + Metastatic TNBC

A Phase II Study of the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Previously Treated Locally Advanced and Metastatic Triple-Negative Breast Cancer

The purpose of this study is to determine the activity of ENMD-2076 as defined by the clinical benefit rate when patients with previously treated locally advanced or metastatic triple negative breast cancer are treated with daily oral ENMD-2076.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: ENMD-2076

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Cancer Hospital of Chinese Academy of Medical Science
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Inidiana University Melvin and Bren Simon Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients must have histologically or cytologically diagnosed locally advanced or metastatic triple-negative breast cancer defined as negative for estrogen receptor, progesterone receptor and HER2.
2. Patients must have measurable disease as defined by revised RECIST criteria (version 1.1, Appendix C) with one or more lesions that can be accurately measured in one or more dimensions within 4 weeks of entry. Areas of previous radiation may not serve as measurable disease.
3. Prior treatment with one to three lines of systemic chemotherapy for locally advanced or metastatic disease and two weeks from any previous anticancer therapy including biologics and recovered from expected toxicity; at least 4 weeks from major surgery and recovered; at least 3 weeks from radiation affecting more than 25% of bone marrow and recovered; and 2 weeks from other palliative radiation and recovered. No more than 450 mg/m2 cumulative dose of doxorubicin is allowed.
4. Because no dosing or adverse event data are currently available on the use of ENMD-2076 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
5. ECOG performance status ≤ 1 (Karnofsky ≥ 70%; see Appendix B).
6. Patients must have normal organ and marrow function
7. Patients must have a pre-study echocardiogram or multigated acquisition (MUGA) scan with an actual left ventricular ejection fraction of greater than or equal to the institution lower limit of normal within one month prior to start of study.
8. If the maximum number of non-biopsy subjects has accrued to the study, willingness to undergo 2 tumor biopsies. NOTE: Tumor biopsies may be required, depending on the number of subjects who have agreed to undergo correlative studies.
9. Ability to tolerate oral medications.
10. Women of child producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential.
11. Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments.
12. Availability of archival tumor tissue (core biopsy or surgical tumor blocks) for analysis. Sites will be asked to submit archival tissue (subjects may start the study if tissue is available at an outside hospital, but not yet requested or received).

Exclusion Criteria:

1. Women who are pregnant or nursing.
2. Have active, acute, or chronic clinically significant infections or bleeding.
3. Have uncontrolled hypertension (systolic blood pressure greater than 150mmHg or diastolic blood pressure greater than 100mmHg); or history of congestive heart failure (equal to or greater than Grade 2).
4. Have active angina pectoris, stroke or recent myocardial infarction (within 6 months).
5. Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec.
6. Have additional uncontrolled serious medical or psychiatric illness.
7. Require therapeutic doses of any anti-coagulant.
8. CNS metastases.
9. Have any medical condition that would impair the administration of oral agents including recurrent bowel obstructions, inflammatory bowel disease or uncontrolled nausea, vomiting or diarrhea.
10. Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of nephrotic syndrome.
11. Have an additional malignancy diagnosed within 5 years of study enrollment with the exception of basal or squamous cell skin cancer or cervical cancer in situ.
12. Patients may not be receiving any other investigational agents.
13. For patients undergoing serial tumor biopsies, known bleeding diathesis or history of abnormal bleeding or require anti-coagulation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ENMD-2076 Treatment; ENMD-2076	Drug: ENMD-2076; 250 mg per day in oral capsules in 28 day continuous cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical benefit rate	24 weeks

Collaborators and Investigators

• Sponsor: CASI Pharmaceuticals, Inc.
• Collaborators: University of Colorado, Denver; Indiana University Melvin and Bren Simon Cancer Center
• Investigators: Study Director: Rong Chen, MD, CASI Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Diamond JR, Eckhardt SG, Pitts TM, van Bokhoven A, Aisner D, Gustafson DL, Capasso A, Sams S, Kabos P, Zolman K, Colvin T, Elias AD, Storniolo AM, Schneider BP, Gao D, Tentler JJ, Borges VF, Miller KD. A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer. Breast Cancer Res. 2018 Aug 2;20(1):82. doi: 10.1186/s13058-018-1014-y.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 12, 2012

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: June 23, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 2076-CL-005