What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma (STS) include chemotherapy agents like doxorubicin and ifosfamide, as well as targeted therapies such as CDK4/6 inhibitors (e.g., Ribociclib) and mTOR inhibitors (e.g., Everolimus). Doxorubicin can cause side effects like myelosuppression, cardiotoxicity, and alopecia. Ifosfamide is associated with myelosuppression, neurotoxicity, and hemorrhagic cystitis. Ribociclib may lead to neutropenia, hepatotoxicity, and QT prolongation. Everolimus can cause stomatitis, infections, hyperglycemia, and pneumonitis. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Soft Tissue Sarcoma (STS). Among these, mTOR inhibitors like Everolimus have shown promise in clinical trials for various cancers, including STS. Another mTOR inhibitor, Sirolimus, has been studied for its effects on malignancies in transplant recipients, which may have implications for STS treatment. While specific CDK4/6 inhibitors like Ribociclib are being actively studied, they have not yet received FDA approval specifically for STS. Other FDA-approved treatments for STS include Pazopanib, a tyrosine kinase inhibitor, and Trabectedin, which is used for advanced liposarcoma and leiomyosarcoma.

What other types of research exist?

Promising novel alternatives for STS patients include MLN0128, an ATP-competitive mTOR kinase inhibitor with potent in vitro and in vivo antitumor activity across multiple sarcoma subtypes, and the combination of selumetinib (a MEK inhibitor) with temsirolimus, which has shown synergistic inhibition of STS cell line growth. Additionally, regorafenib has demonstrated improved progression-free survival in nonadipocytic STS subtypes.

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mTOR Inhibitor

Ribociclib + Everolimus for Dedifferentiated Liposarcoma and Leiomyosarcoma

Phase 2

Waitlist Available

Led By Margaret von Mehren, MD

Research Sponsored by Fox Chase Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have locally advanced, metastatic or refractory leiomyosarcoma or dedifferentiated liposarcoma

Patient has adequate bone marrow and organ function as defined by specified laboratory values at screening

Must not have

Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality

Previous treatment with CDK4/6 inhibitors or mTOR inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after final treatment on study

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, Ribociclib and Everolimus, in patients with advanced DDL and LMS who have not responded to previous treatments. Ribociclib blocks proteins that help cancer grow, while Everolimus stops cancer cells from multiplying. Everolimus is an oral mTOR inhibitor that is approved for various cancers, including renal cell carcinoma and breast cancer.

Who is the study for?

Adults with advanced dedifferentiated liposarcoma (DDL) or leiomyosarcoma (LMS) who've had at least one prior systemic therapy can join this trial. They should be in good physical condition, able to take oral medication, and have measurable disease progression after their last treatment. Women must not be pregnant or nursing, and all participants must agree to use effective contraception.

What is being tested?

The study is testing a combination of two drugs: Ribociclib taken orally for three weeks with a one-week break, and Everolimus taken continuously every day. The goal is to see how well these drugs work together against DDL and LMS by monitoring tumor response using scans at specific intervals.

What are the potential side effects?

Possible side effects include risks associated with bone marrow suppression which could lead to blood disorders, organ dysfunction due to the drug's toxicity, gastrointestinal issues affecting absorption of the drugs, heart problems including abnormal heart rhythms, and potential interactions with other medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is a type of sarcoma that has spread or is not responding to treatment.

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My blood tests show my organs and bone marrow are working well.

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My cancer has worsened or returned after my last treatment.

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I am fully active or can carry out light work.

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I can swallow pills without difficulty.

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My leiomyosarcoma tumor has normal Rb protein levels.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have uncontrolled heart disease or abnormal heart rhythms.

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I have been treated with CDK4/6 or mTOR inhibitors before.

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I have recently undergone radiotherapy.

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I still have side effects from cancer treatment that are not mild.

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I am a sexually active male not using condoms.

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My liver disease is moderately to severely advanced.

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I am of childbearing age and not using effective birth control.

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I am allergic to ingredients in Ribociclib or Everolimus.

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I am currently taking warfarin or a similar blood thinner.

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I have a known history of HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 16 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~16 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 16 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

Number of participants with treatment-related adverse events

Objective response rate (ORR)

Overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Leiomyosarcoma ArmExperimental Treatment2 Interventions

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.

Group II: Dedifferentiated Liposarcoma ArmExperimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ribociclib

2018

Completed Phase 3

~2420

Everolimus

2010

Completed Phase 4

~1510

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ribociclib, a CDK4/6 inhibitor, blocks cyclin-dependent kinases 4 and 6, halting cancer cell proliferation by disrupting the cell cycle. Everolimus, an mTOR inhibitor, targets the mTOR pathway, which is crucial for cell growth and survival, thereby reducing tumor growth and proliferation. These targeted therapies are significant for Soft Tissue Sarcoma patients as they provide more precise treatment options, potentially improving outcomes and reducing side effects compared to traditional chemotherapy.

Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus.A Translational, Pharmacodynamic, and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer.The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma.