Estrogen-receptor Positive Invasive Metastatic Breast CancerPhase 2NCT01594216
Ruxolitinib in Estrogen Receptor Positive Breast Cancer
A Phase 2 study testing Ruxolitinib and Exemestane in people with Estrogen-receptor Positive Invasive Metastatic Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Estrogen-receptor Positive Invasive Metastatic Breast Cancer
- What is being tested?
- Ruxolitinib and Exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to 9 Apr 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 10104
About this study
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)
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).
Read the detailed description
In vitro mechanisms link IL-6 to poor outcome in breast cancer via activated JAK/STAT tumor signaling, leading to an aggressive tumor phenotype, and our preliminary data support these mechanisms in women with ER+ disease. Our overarching hypotheses are that (1) IL-6 mediates upregulation of JAK/STAT signaling pathways that leads to poor prognosis in women with ER-positive disease, (2) blockade of JAK/STAT signaling, via JAK inhibition, in patients with activating IL-6 polymorphisms and/or upregulation of STAT3 tumor signaling will enhance the response to endocrine therapy, and (3) patients likely to respond to JAK inhibition can be identified by germline genotyping for IL-6 variants, and effectiveness of the targeted therapy will be measurable through tumor assessment of activated STAT signaling through upregulation of phospho- STAT3 and expression of STAT3 target genes.
We now propose a trial to determine whether addition of the JAK inhibitor, Ruxolitinib (INCB018424), enhances the activity of exemestane alone in women with ER-positive breast cancer who have relapsed after non-steroidal aromatase inhibitor and carry a germline polymorphism in IL-6, and to determine if tumor activation of STAT3 can identify patients most likely to respond to the combination.
- Being tested
- Ruxolitinib, Exemestane
- Keywords
- Postmenopausal female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
ExemestaneDrug
| Study group | Role | What they receive |
|---|---|---|
| First Stage | Experimental | Ruxolitinib at 25 mg orally, twice daily and Exemestane, 25 mg orally once daily Receives: Drug: Ruxolitinib; Drug: Exemestane |
| Second Stage | Experimental | Ruxolitinib at 15 mg orally, twice daily and Exemestane, 25 mg orally once daily Receives: Drug: Ruxolitinib; Drug: Exemestane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Safety will be assessed by evaluation of the number and severity adverse events as defined by the NCI CTCAE Version 4.0
Measured: 3 years
Time to Progression
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 3 years
Secondary outcomes (2)
Pharmacodynamic Assessment of Phospho-STAT3 Inhibition
Measured: 3 years
Inflammatory Markers
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2012 (estimated)
- Study startApr 2012
- Primary completionApr 2016
- Study completion9 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Estrogen-receptor Positive Invasive Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angela DiMichele, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01594216
- Sponsor's protocol ID
- UPCC 02112
- Status last verified
- May 2024
- First submitted
- 7 May 2012
- Last updated
- 12 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01594216
- Acronym / sponsor ID
- UPCC 02112
- Keywords
- Postmenopausal female
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- 9 Apr 2016 (actual)
- First posted
- 9 May 2012 (estimated)
- Results
- Posted 12 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
In vitro mechanisms link IL-6 to poor outcome in breast cancer via activated JAK/STAT tumor signaling, leading to an aggressive tumor phenotype, and our preliminary data support these mechanisms in women with ER+ disease. Our overarching hypotheses are that (1) IL-6 mediates upregulation of JAK/STAT signaling pathways that leads to poor prognosis in women with ER-positive disease, (2) blockade of JAK/STAT signaling, via JAK inhibition, in patients with activating IL-6 polymorphisms and/or upregulation of STAT3 tumor signaling will enhance the response to endocrine therapy, and (3) patients likely to respond to JAK inhibition can be identified by germline genotyping for IL-6 variants, and effectiveness of the targeted therapy will be measurable through tumor assessment of activated STAT signaling through upregulation of phospho- STAT3 and expression of STAT3 target genes.
We now propose a trial to determine whether addition of the JAK inhibitor, Ruxolitinib (INCB018424), enhances the activity of exemestane alone in women with ER-positive breast cancer who have relapsed after non-steroidal aromatase inhibitor and carry a germline polymorphism in IL-6, and to determine if tumor activation of STAT3 can identify patients most likely to respond to the combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| First Stage | Experimental | Drug: Ruxolitinib, Drug: ExemestaneRuxolitinib at 25 mg orally, twice daily and Exemestane, 25 mg orally once daily |
| Second Stage | Experimental | Drug: Ruxolitinib, Drug: ExemestaneRuxolitinib at 15 mg orally, twice daily and Exemestane, 25 mg orally once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ruxolitinib | Drug | First Stage, Second Stage |
| Exemestane | Drug | First Stage, Second Stage |
Primary outcome
Number of Participants With Adverse Events
Time frame: 3 years
Safety will be assessed by evaluation of the number and severity adverse events as defined by the NCI CTCAE Version 4.0
Time to Progression
Time frame: 3 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
2 secondary outcomes
Pharmacodynamic Assessment of Phospho-STAT3 Inhibition
Time frame: 3 years
Inflammatory Markers
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Estrogen-receptor Positive Invasive Metastatic Breast Cancer
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Metastatic Breast Cancer, ER Positive Breast Cancer
RecruitingObservational study
Longitudinal Tumor Burden Quantification Using Circulating Tumor DNA in Metastatic Lobular Breast Cancer
Metastatic Invasive Lobular Carcinoma (mILC)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela DiMichele, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib and Exemestane in people with Estrogen-receptor Positive Invasive Metastatic Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.