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Soft Tissue SarcomaPhase 2NCT03114527

Phase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)

A Phase 2 study testing Ribociclib and Everolimus in people with Soft Tissue Sarcoma, run by Fox Chase Cancer Center at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a two center, 2 arm, Phase II study evaluating the combination of Ribociclib and Everolimus in patients with advanced DDL and LMS who have had at least 1 prior systemic therapy. Patients will be enrolled by sarcoma histology into DDL (Arm A) and LMS (Arm B). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Ribociclib and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
2 sitesUnited States
Study dates
8 Aug 2017to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Male or female patients 18 years or older.
  • Patients must have locally advanced, metastatic or refractory leiomyosarcoma or dedifferentiated liposarcoma.
  • A) Patients enrolled into the dedifferentiated cohort do not require prior systemic therapy (may be naive to systemic therapy). B) Leiomyosarcoma patients must have had at least 1 prior systemic therapy (does not include adjuvant/neoadjuvant therapy in a curative setting). There is no limits on prior number of therapies for either cohort.
  • Measurable disease per RECIST 1.1
  • Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment.
  • Time since the last prior therapy to treat underlying malignancy to start of drug:
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  • Cytotoxic chemotherapy: greater than the duration of the most recent cycle of the previous regimen (with a minimum of two weeks for all)
  • Biologic therapy (e.g., antibodies): ≥ four weeks
  • ≥ 5 x t1/2 of a small molecule therapeutic, not otherwise defined above, with a minimum of 2 weeks (including aromatase inhibitors and tamoxifen).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements.
  • Patient has adequate bone marrow and organ function as defined by the following laboratory values at screening:
  • Absolute neutrophil count ≥1.5 × 109/L
  • Platelets ≥100 × 109/L
  • Hemoglobin ≥9.0 g/dL
  • Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
  • INR ≤1.5
  • Serum creatinine <1.5 mg/dL or creatinine clearance ≥50 mL/min
  • In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and AST <5 x ULN
  • Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
  • Fasting plasma glucose <140 mg/dL / 7.7 mmol/L and Glycosylated Hemoglobin (HbA1c) ≤ 8% (both criteria have to be met)
  • Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy and when the above mentioned values have been achieved.
  • Must be able to swallow ribociclib and everolimus capsules/tablets.
  • Patients with leiomyosarcoma must have tumors with intact Rb as documented by protein expression by IHC for study entry. Patients without sufficient archival tissue for testing will not be eligible. Please see Section 9.0 for further details on testing and interpretation of results. In the event that a patient has prior sequencing information (i.e. through commercial testing) suggestive of intact Rb, the patient may be included into the study on a case by case basis as determined by the principle investigators. The patient will still be required to submit tissue for Rb determination by IHC, but will not need to wait for these results for study entry.

Who cannot join

  • Patient has a known hypersensitivity to any of the excipients of Ribociclib or Everolimus.
  • Previous treatment with CDK4/6 inhibitors or mTOR inhibitors.
  • Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
  • Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
  • At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
  • Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme- inducing anti-epileptic medications for brain metastases.
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  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patient has a known history of HIV infection (testing not mandatory).
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
  • History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within 6 months prior to study entry.
  • Documented cardiomyopathy
  • Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
  • History of cardiac failure, significant/symptomatic bradycardia, Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:
  • Known risk to prolong the QT interval or induce Torsade's de Pointes.
  • Uncorrected hypomagnesemia or hypokalemia.
  • Systolic Blood Pressure (SBP) >160 mmHg or <90 mmHg.
  • Bradycardia (heart rate <50 at rest), by ECG or pulse.
  • On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 (based on a mean of 3 ECGs).
  • Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug (see Table 4 for details):
  • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
  • That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • Herbal preparations/medications, dietary supplements. Acceptable supplements include multivitamins, vitamin D and calcium
  • Angiotensin-converting enzyme (ACE) inhibitor therapy
  • Receipt of a live vaccine within 30 days prior to starting study drug. Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.
  • Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
  • The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
  • Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
  • Treatment with an investigational agent within 30 days prior or within 5 half-lives (whichever is longer) before the first dose of the study drug.
  • Patient who has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug, and who has not recovered to Grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom ≥25% of the bone marrow (Ellis, 1961) was irradiated.
  • Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
  • Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 Grade ≤1 (Exception to this criterion: patients with any Grade of alopecia are allowed to enter the study).
  • Patient with a Child-Pugh score B or C. See Appendix A.
  • Patient has a history of non-compliance to medical regimen or inability to grant consent.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for at least 3 months after completion of treatment. Highly effective contraception methods include:
  • Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient
  • Use of 1 highly effective method of contraception, and 1 additional (barrier) method, at the same time
  • Highly effective methods: Intra-uterine devices (IUD), Hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants) Other effective methods (barrier methods): Latex condom, Diaphragm with spermicide; Cervical cap; Sponge
  • 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 ago. 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.
  • Sexually active males unless they use a condom during intercourse while taking the drug and for 21 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: Phase II Trial of Ribociclib in Combination With Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)

This is a two center, 2 arm, Phase II study evaluating the combination of Ribociclib and Everolimus in patients with advanced DDL and LMS who have had at least 1 prior systemic therapy. Patients will be enrolled by sarcoma histology into DDL (Arm A) and LMS (Arm B). The purpose of this study is to determine the anti-tumor activity of this doublet therapy in these patient cohorts. Ribociclib will be administered orally at 300 mg/day 3 weeks on/1 week off. Everolimus will be administered 2.5 mg orally on a continuous 28 day cycle. Clinical and laboratory assessments will be made on day 1, d15 of cycle 1 and 2, and day 1 of each subsequent cycle. Tumor response will be assessed by RECIST 1.1 at (CT or MRI) at week 8, 16, 24 and every 12 weeks thereafter. Study drug administration will continue until disease progression, unacceptable toxicity or withdrawal of consent. Patients will be followed until death or are lost to follow-up for analysis of secondary endpoints.

There will be a 1 step registration process for dedifferentiated liposarcoma patients while patients with leiomyosarcoma will require a 2 step registration process. For step 1 of registration, patients must meet all the eligibility criteria necessary for step 1. For step 2 registration, patients must meet the inclusion criteria necessary for step 2 to be enrolled into the study.

Being tested
Ribociclib, Everolimus
Keywords
Dedifferentiated liposarcoma, DDL, Leiomyosarcoma, LMS, Ribociclib
Medical subject headings
Sarcoma, Liposarcoma, Leiomyosarcoma

What participants receive

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

  • RibociclibDrug

    Also called LEE011

    Orally bioavailable, highly selective small molecule inhibitor of CDK4/6

  • EverolimusDrug

    Also called RAD001, Afinitor

    mTOR inhibitor

Study groups in NCT03114527
Study groupRoleWhat they receive
Dedifferentiated Liposarcoma ArmExperimentalPatients receive ribociclib orally at 300mg/day for 21 days of each 28 day cycle and everolimus 2.5mg orally on a continuous 28 day cycle.
Receives: Drug: Ribociclib; Drug: Everolimus
Leiomyosarcoma ArmExperimentalPatients receive ribociclib orally at 300mg/day for 21 days of each 28 day cycle and everolimus 2.5mg orally on a continuous 28 day cycle.
Receives: Drug: Ribociclib; Drug: Everolimus

What is being measured

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

  1. Antitumor activity of Ribociclib in combination with Everolimus in advanced LMS or DDL

    Progression free rate

    Measured: 16 weeks

Secondary outcomes (4)

  1. Objective response rate (ORR)

    ORR will be measured by RECIST 1.1.

    Measured: Through study completion

  2. Progression-free survival (PFS)

    PFS will be measured by RECIST 1.1.

    Measured: Through study completion

  3. Overall survival (OS)

    OS will be measured from the time of initiation of treatment until death

    Measured: Through study completion

  4. Number of participants with treatment-related adverse events

    Treatment-related adverse events will be assessed by CTCAE v4.03

    Measured: Up to 30 days after final treatment on study

Timeline

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

  1. First posted14 Apr 2017
  2. Study start8 Aug 2017
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03114527
Sponsor's protocol ID
SAR-096
Other IDs
17-1013
Status last verified
May 2026
First submitted
23 Mar 2017
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ribociclib and Everolimus in people with Soft Tissue Sarcoma, run by Fox Chase Cancer Center at 2 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 24 inclusion and 43 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: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

This study is still under way. Results are not available in the source record yet.

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?

Antitumor activity of Ribociclib in combination with Everolimus in advanced LMS or DDL (time frame: 16 weeks). 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 NCT03114527.

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 22 May 2026.

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