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

NCT03114527 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: SAR-09617-1013
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief 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). 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.

Conditions

Soft Tissue Sarcoma

Keywords

Dedifferentiated liposarcoma; DDL; Leiomyosarcoma; LMS; Ribociclib

Outcome Measures

Primary Outcomes (1)

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

  Progression free rate

  16 weeks

Secondary Outcomes (4)

• Objective response rate (ORR)

  Through study completion

• Progression-free survival (PFS)

  Through study completion

• Overall survival (OS)

  Through study completion

• Number of participants with treatment-related adverse events

  Up to 30 days after final treatment on study

Study Arms (2)

Dedifferentiated Liposarcoma Arm

EXPERIMENTAL

Patients 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.

Drug: Ribociclib; Drug: Everolimus

Leiomyosarcoma Arm

EXPERIMENTAL

Patients 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.

Drug: Ribociclib; Drug: Everolimus

Interventions

Ribociclib DRUG

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

Also known as: LEE011

Dedifferentiated Liposarcoma Arm; Leiomyosarcoma Arm

Everolimus DRUG

mTOR inhibitor

Also known as: RAD001, Afinitor

Dedifferentiated Liposarcoma Arm; Leiomyosarcoma Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Sarcoma; Liposarcoma; Leiomyosarcoma

Interventions

ribociclib; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Adipose Tissue; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Margaret von Mehren, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 14, 2017
• Study Start: August 8, 2017
• Primary Completion: November 12, 2020
• Study Completion: December 1, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Locations

US (2)