Ruxolitinib in Estrogen Receptor Positive Breast Cancer

• ClinicalTrials.gov Identifier: NCT01594216
• Recruitment Status: Completed
• First Posted: May 9, 2012
• Last Update Posted: May 5, 2020
• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Information provided by (Responsible Party): Abramson Cancer Center of the University of Pennsylvania

Study Description

Brief Summary:

This is a Phase II investigator-Initiated trial of the Investigational Drug, Ruxolitinib, in combination with Exemestane in patients with estrogen-receptor positive advanced breast cancer. The objective of this study is to determine the preliminary safety and efficacy of the combination of exemestane and Ruxolitinib (INCB018424).

Condition or disease	Intervention/treatment	Phase
Estrogen-receptor Positive Invasive Metastatic Breast Cancer	Drug: Ruxolitinib; Drug: Exemestane	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial Of The JAK-Inhibitor Ruxolitinib (INCB018424) In Combination With Exemestane For Patients With Estrogen Receptor (ER) Positive Advanced Breast Cancer)
• Study Start Date: April 2012
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 9, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: First Stage; Ruxolitinib at 25 mg orally, twice daily and Exemestane, 25 mg orally once daily	Drug: Ruxolitinib; Drug: Exemestane
Experimental: Second Stage; Ruxolitinib at 15 mg orally, twice daily and Exemestane, 25 mg orally once daily	Drug: Ruxolitinib; Drug: Exemestane

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events [ Time Frame: 3 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically-confirmed, invasive metastatic breast cancer.
• Estrogen-receptor positivity (defined by at least 5% staining by immunohistochemistry) on either the primary breast tumor or a metastatic biopsy.
• Postmenopausal status, defined as: either "surgical menopause" via oophorectomy, or "natural menopause" in which the patient has had no menses in the previous 12-month period. Premenopausal patients who have been been rendered amenorrheaic by tamoxifen must have a serum estradiol level <30 pg/ml after discontinuation of tamoxifen. Amenorrheaic premenopausal subjects must have a negative pregnancy test during screening (prior to enrollment) and must be advised to use adequate contraception throughout their participation.
• Prior therapy for the current malignancy: Patient must have 1) relapsed on or within 2 years of completing adjuvant hormonal therapy with a non-steroidal aromatase inhibitor, OR 2) failed a non-steroidal aromatase inhibitor in the metastatic setting. There is no limit to prior chemotherapy or hormonal regimens for this malignancy.
• At least one measureable lesion by RECIST or mainly lytic bone lesions in the absence of measurable disease. Bone-only disease is allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function, defined as follows:

Bilirubin ≤ 1.5 x the upper limit of normal (ULN) Serum creatinine ≤ 1.5 x UNL or calculated creatinine clearance ≥ 60 mL/min, and

• For subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
• For subjects with liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase ≤ 5 x ULN
• Adequate bone marrow function, defined as follows Absolute neutrophil count (ANC) >1500/mm3 Hemoglobin > 9 Platelets >100,000/mm3
• The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.

EXCLUSION CRITERIA:

• Chemotherapy, hormonal therapy or investigational anti-tumor therapy within 21 days of starting study treatment. Use of bone-building agents is allowed.
• Prior treatment with exemestane.
• Any type of investigational agent within 28 days before the first dose of study treatment.
• Unresolved clinically-meaningful toxicity due to prior therapy. Toxicity from previous treatment must be back to baseline or Grade ≤ 1, with the exception of neurotoxicity and alopecia.
• Untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease. Patients who have stable disease after radiotherapy for CNS disease are eligible. Testing for brain involvement in the absence of symptoms is not required as part of this protocol.
• Uncontrolled, intercurrent illness
• Known ongoing or active infection, including active hepatitis B or hepatitis C. Testing for hepatitis B or C is not required as part of this protocol.
• Uncontrolled diabetes mellitus
• Uncontrolled hypertension
• Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
• A baseline corrected QT interval (QTc) > 470 ms.
• The subject is known to be positive for the human immunodeficiency virus (HIV). Note: baseline HIV screening is not required
• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Contacts and Locations

Locations

United States, Pennsylvania

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 10104

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Angela DiMichele, MD; Abramson Cancer Center of the University of Pennsylvania

More Information

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01594216
• Other Study ID Numbers: UPCC 02112
• First Posted: May 9, 2012
• Last Update Posted: May 5, 2020
• Last Verified: April 2020

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:

Postmenopausal female

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Exemestane; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs