Sporadic Angiomyolipomas (AMLs)Phase 2SAGENCT02539459

Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus

A Phase 2 study testing Everolimus in people with Sporadic Angiomyolipomas (AMLs), run by Fox Chase Cancer Center at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Sporadic Angiomyolipomas (AMLs)
What is being tested?: Everolimus
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 8 sitesUnited States
Study dates: 23 Sep 2015to 20 Aug 2018
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
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Must have a diagnosis of renal AML > 3 cm confirmed on pre-enrollment Dynamic Contrast Enhanced MRI (DCE-MRI)
Must not have received any prior treatment for AML
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Absolute neutrophil count >= 1,500/ microliter (mcL)
Hemoglobin >=10 g/dL
Platelets >= 100,000/ mcL

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international normalized ratio (INR) <= 1.2 X Upper limit Normal (ULN)
activated partial thromboplastin time (aPTT) <= 1.2 X ULN
aspartate aminotransferase (AST) / alanine transaminase (ALT) <= 2.5 X ULN
Total bilirubin <= 2.0mg/dL
Renal Function epidermal growth factor receptor (eGFR) >= 30 mL/min via calculated creatinine clearance
Fasting serum cholesterol <= 300 mg/dL OR <= 7.75 mmol/L AND fasting triglycerides <= 2.5x ULN.

Who cannot join

History of tuberous sclerosis, LAM or any active malignancy
Treatment with any other investigational agents for any other disease
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product
Active diarrhea of any grade.
History of human immunodeficiency virus (HIV) infection, hepatitis B or C (screening for all three is mandatory prior to study); prior hepatitis C infection
Presence of any active or ongoing infection.

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Any known uncontrolled underlying pulmonary disease by history, physical exam or if applicable pulmonary function test (PFTs)
History of certain cardiovascular conditions within the past 6 months
History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure.
History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
Corrected QT interval (QTc) > 480 milliseconds
Poorly controlled hypertension, defined as systolic blood pressure (SBP) of >= 140 millimeters of mercury(mmHg) or diastolic blood pressure (DBP) of >= 90 mmHg.
Evidence of active bleeding or bleeding diathesis
Uncontrolled diabetes mellitus (defined by a Hgb A1c >8) obtained within 14 days prior to registration. Optimal glucose control (Hgb A1c <= 8) must be achieved before registration and monitored during protocol treatment
Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
Unable or unwilling to discontinue use of prohibited medications
Concurrent therapy given to treat cancer including treatment with an investigational agent or concurrent participation in another clinical trial involving anti-cancer investigational drug.
Administration of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to everolimus
Prior or current use of systemic anti-vascular endothelial growth factor (VEGF) inhibitors, cytokines or mechanistic target of rapamycin (mTOR) inhibitors (e.g. interferon, interleukin 2).
Pregnant or nursing (lactating) women
Women of child-bearing potential (WOCBP) must use highly effective methods of contraception during the study and 8 weeks after.
Unable to obtain a contrast (gadolinium) based DCE MRI, including include patients with pacemakers, automatic implantable cardioverter/defibrillator (AICDs), non MRI compatible metallic implants or eGFR <30.
Must not have received immunization with an attenuated live vaccine within seven days prior to registration nor have plans to receive such vaccination while on protocol treatment
Must not be taking, nor plan to take while on protocol treatment, strong cytochrome P450 3A4 (CYP3A4) inhibitors, (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, fluvoxamine, nefazodone, nelfinavir, ritonavir) and/or strong CYP3A4 inducers (e.g. phenytoin, rifampin, rifabutin) within 14 days prior to randomization.
History of another primary malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for >= 3 years
Childs-Pugh A-C liver disease (Appendix II)

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

Dana Farber Cancer Institute
Boston, Massachusetts
Duke University Health System
Durham, North Carolina
M D Anderson Cancer Center
Houston, Texas
Yale School of Medicine
New Haven, Connecticut
Memorial Sloan Kettering
New York, New York
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pennsylvania
Philadelphia, Pennsylvania
Mayo Clinic
Rochester, Minnesota

Other trials in United States

About this study

Official title: A Phase II Study of Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus Therapy

The purpose of this research study is to see if oral everolimus is tolerable and effective in the treatment of sporadic Angiomyolipomas (AMLs). AMLs are the most common non-cancerous tumor of the kidney. They are composed of blood vessels, muscle cells and fat cells.Everolimus is already an approved drug for several other diseases like kidney cancer, but is being studied now specifically to see if it is helpful for people with AML.

Read the detailed description

Primary Objective

To evaluate the efficacy and tolerability of everolimus in reducing tumor volume in sporadic AMLs as measured by dynamic contrast enhanced magnetic resonance imaging (DCE MRI), in patients who might otherwise be considered for active surgical or percutaneous intervention.

Secondary Objectives

To evaluate health-related quality of life (HRQoL) in subjects treated with everolimus for sporadic AMLs.
To assess the growth kinetics of sporadic AMLs in patients who have been treated with everolimus as part of the study and demonstrate an objective response as well as those who have been treated with everolimus during the study with a suboptimal or no response.
To measure the rate of surgical or percutaneous (embolization) intervention at 1 year from day 1 of study.
To assess the safety and tolerability of everolimus in patients with sporadic AML.

Conditions: Sporadic Angiomyolipomas (AMLs)
Being tested: Everolimus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EverolimusDrug
10 mg tablets

Study groups in NCT02539459
Study group	Role	What they receive
Treatment (everolimus)	Experimental	Patients will take 10 mg (1 tablet) of everolimus each day for 4 months Receives: Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients With Tumor Volume Reduction Greater Than 25%
Measuring the efficacy and tolerability of everolimus by measuring the number of patients with tumor volume reduction greater than 25% in sporadic AMLs as measured by DCE MRI
Measured: 12 months

Secondary outcomes (1)

Safety and Tolerability of Everolimus in Patients With Sporadic AML
Number of participants with treatment-related adverse events requiring dose reduction or study withdrawal as assessed by Common Toxicity Criteria for Adverse Effects (CTCAE v4.0)
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Sep 201520 Aug 2018

First posted3 Sep 2015 (estimated)
Study start23 Sep 2015
Primary completion20 Aug 2018
Study completion20 Aug 2018

Why it stopped: Extreme toxicity, met toxicity stopping rules

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Sporadic Angiomyolipomas (AMLs)Studies of the same condition, open and under way.
More trials run by Fox Chase Cancer CenterThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02539459
Sponsor's protocol ID: GU-070
Acronym: SAGE
Status last verified: Dec 2022
First submitted: 20 Aug 2015
Last updated: 15 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Geynisman DM, Kadow BT, Shuch BM, Boorjian SA, Matin SF, Rampersaud E, Milestone BN, Plimack ER, Zibelman MR, Kutikov A, Smaldone MC, Chen DY, Viterbo R, Joshi S, Greenberg RE, Malizzia L, McGowan T, Ross EA, Uzzo RG. Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial. J Urol. 2020 Sep;204(3):531-537. doi: 10.1097/JU.0000000000001065. Epub 2020 Apr 6.
PubMed 32250730

Study at a glance

From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus Therapy
ClinicalTrials.gov ID: NCT02539459
Acronym / sponsor ID: SAGE / GU-070
Conditions: Sporadic Angiomyolipomas (AMLs)
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Extreme toxicity, met toxicity stopping rules
Enrolment: 20 participants (actual)
Lead sponsor: Fox Chase Cancer CenterUniversity, hospital or other
Collaborators: Novartis Pharmaceuticals
Study start: 23 Sep 2015 (actual)
Primary completion: 20 Aug 2018 (actual)
Study completion: 20 Aug 2018 (actual)
First posted: 3 Sep 2015 (estimated)
Results: Posted 17 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Primary Objective

To evaluate the efficacy and tolerability of everolimus in reducing tumor volume in sporadic AMLs as measured by dynamic contrast enhanced magnetic resonance imaging (DCE MRI), in patients who might otherwise be considered for active surgical or percutaneous intervention.

Secondary Objectives

To evaluate health-related quality of life (HRQoL) in subjects treated with everolimus for sporadic AMLs.
To assess the growth kinetics of sporadic AMLs in patients who have been treated with everolimus as part of the study and demonstrate an objective response as well as those who have been treated with everolimus during the study with a suboptimal or no response.
To measure the rate of surgical or percutaneous (embolization) intervention at 1 year from day 1 of study.
To assess the safety and tolerability of everolimus in patients with sporadic AML.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (everolimus)	Experimental	Drug: EverolimusPatients will take 10 mg (1 tablet) of everolimus each day for 4 months

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Must have a diagnosis of renal AML > 3 cm confirmed on pre-enrollment Dynamic Contrast Enhanced MRI (DCE-MRI)
Must not have received any prior treatment for AML
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Absolute neutrophil count >= 1,500/ microliter (mcL)
Hemoglobin >=10 g/dL

Key exclusion criteria (27 listed)

History of tuberous sclerosis, LAM or any active malignancy
Treatment with any other investigational agents for any other disease
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product
Active diarrhea of any grade.
History of human immunodeficiency virus (HIV) infection, hepatitis B or C (screening for all three is mandatory prior to study); prior hepatitis C infection

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
Everolimus10 mg tablets	Drug	Treatment (everolimus)

Primary outcome

Number of Patients With Tumor Volume Reduction Greater Than 25%
Time frame: 12 months
Measuring the efficacy and tolerability of everolimus by measuring the number of patients with tumor volume reduction greater than 25% in sporadic AMLs as measured by DCE MRI

1 secondary outcome

Safety and Tolerability of Everolimus in Patients With Sporadic AML
Time frame: 12 months

Results and safety

Results posted to the registry on 17 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment (Everolimus)	20	18

Primary outcome: Number of Patients With Tumor Volume Reduction Greater Than 25%

Time frame: 12 months. Count of participants. Unit: Participants

Measure	Treatment (Everolimus) n = 10
Value	5

Population analysed: Some participants experienced adverse events and were withdrawn from the study, and therefore tumor volume reduction was not measured in these patients.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment (Everolimus)	3 of 20 (15%)	20 of 20 (100%)	0 of 20

Limitations and caveats (from the sponsor): Lack of tissue to correlate response to molecular markers of aberrant mTOR pathways. Lack for serum everolimus levels. Clinical significance of 25% volume reduction unknown. Patient withdrawals and incomplete protocol imaging.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 32250730Geynisman DM, Kadow BT, Shuch BM, Boorjian SA, Matin SF, Rampersaud E, Milestone BN, Plimack ER, Zibelman MR, Kutikov A, Smaldone MC, Chen DY, Viterbo R, Joshi S, Greenberg RE, Malizzia L, McGowan T, Ross EA, Uzzo RG. Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial. J Urol. 2020 Sep;204(3):531-537. doi: 10.1097/JU.0000000000001065. Epub 2020 Apr 6.

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.

Robert G Uzzo, MD principal investigator

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus in people with Sporadic Angiomyolipomas (AMLs), run by Fox Chase Cancer Center at 8 sites 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 27 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: stopped early, as of the sponsor's last update on 15 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites 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 17 Feb 2021). 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 Patients With Tumor Volume Reduction Greater Than 25% (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02539459, which also lists 1 linked publication.

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 15 Dec 2022.