What is the mechanism of action of this treatment?

Common treatments for Ewing Sarcoma include chemotherapy agents like gemcitabine, which incorporates into DNA and disrupts replication, leading to cell death. Novel agents like LY2880070, though not fully detailed, likely target specific pathways critical for cancer cell survival. Other treatments, such as nab-paclitaxel, disrupt microtubule function, and PARP inhibitors like talazoparib enhance DNA damage. These mechanisms are vital for Ewing Sarcoma patients as they exploit the cancer's rapid cell division and genetic instability, potentially improving treatment efficacy and patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for Ewing Sarcoma often include chemotherapy agents such as gemcitabine, sometimes in combination with other drugs like docetaxel. Known side effects of gemcitabine include severe fatigue, nausea, vomiting, and neutropenia (a decrease in white blood cells). When combined with other agents, additional side effects may include edema, constitutional symptoms, and increased toxicity leading to treatment discontinuation. These side effects are important considerations for patients undergoing treatment and should be discussed with their healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for Ewing Sarcoma, primarily focusing on multi-agent chemotherapy regimens. Commonly used drugs include vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. While gemcitabine is used in various sarcomas, there is no specific mention of its FDA approval for Ewing Sarcoma. Novel therapeutic agents like LY2880070 are still under investigation and have not yet received FDA approval for this indication.

What other types of research exist?

Promising novel alternatives for Ewing Sarcoma treatment include STK899704, BO-1055, and the combination of temozolomide and irinotecan. These agents have shown significant efficacy in preclinical and clinical studies.

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Anti-metabolites

LY2880070 + Gemcitabine for Ewing Sarcoma

Phase 2

Recruiting

Led By Emily Slotkin, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Organ Function Requirements: Adequate bone marrow function defined as: Absolute neutrophil count (ANC) ≥ 1500/mm3. Platelet count ≥ 100,000/mm3. Hemoglobin ≥ 8 g/dl. Adequate renal function defined as estimated glomerular filtration (eGFR) rate ≥ 60 mL/min/1.73m2: as estimated by CKD-EPI equation for patients ≥ 18 years of age OR As estimated by cystatin C for patients < 18 years of age. Adequate liver function defined as: Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for age. AST or ALT ≤ 2.5 x upper limit of normal for patients without liver metastases. AST or ALT ≤ 5 x upper limit of normal for patients with liver metastases. Serum albumin ≥ 2.5 g/dl. Adequate cardiac function defined as: Left ventricular ejection fraction (LVEF) >45% as measured on echocardiogram, cardiac MRI, or MUGA. QTc < 470 ms on screening 12 lead electrocardiogram. Pregnancy/Contraception: Post-menarchal females must have a negative urine or serum pregnancy test at screening and ≤ 24 hours prior to study treatment. Males or females of reproductive potential must be willing to use a barrier method of contraception throughout the course of the study and for 6 months after completing study treatment

Therapeutic options: patient's current disease state must be one which has failed standard cytotoxic chemotherapy including cyclophosphamide/doxorubicin/vincristine and ifosfamide/etoposide

Must not have

Patients who have an uncontrolled infection

Patients who have a history of Torsades de Pointes, carry a diagnosis of congestive heart failure, or have a family history of prolonged QT syndrome

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether a new drug, LY2880070, combined with the chemotherapy drug gemcitabine, can effectively treat Ewing sarcoma or Ewing-like sarcoma. These cancers are tough to treat, and the combination aims to stop cancer cells from growing and dividing more effectively than current treatments. Gemcitabine is an active drug in advanced breast cancer both as a single agent and in combination with other chemotherapeutic agents.

Who is the study for?

This trial is for individuals of any age who weigh at least 40 kg and can swallow capsules. They must have Ewing sarcoma or similar, with measurable disease confirmed by specific molecular features. Participants need to be relatively healthy (Karnofsky ≥70% or Lansky ≥70), have adequate organ function, and no more than four prior cancer treatments. Pregnant individuals, those with certain heart conditions, uncontrolled infections, or hypersensitivity to gemcitabine are excluded.

What is being tested?

The study tests the effectiveness of LY2880070 combined with chemotherapy drug gemcitabine in treating advanced Ewing sarcoma and related diseases. It aims to determine if this combination therapy can provide a new treatment option for patients who have not responded well to standard therapies.

What are the potential side effects?

Potential side effects may include reactions typical of chemotherapy such as nausea, fatigue, low blood counts leading to increased infection risk or bleeding problems. Specific side effects from LY2880070 are not detailed but could resemble other targeted cancer drugs' profiles.

Eligibility Criteria

Inclusion Criteria

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

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My cancer did not respond to standard chemotherapy treatments.

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My cancer is a specific type called Ewing sarcoma, confirmed by a test.

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My cancer can be measured using standard criteria.

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I am mostly active and can care for myself.

Exclusion Criteria

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

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I do not have any infections that are currently uncontrolled.

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I have a history of heart issues including Torsades de Pointes, congestive heart failure, or a family history of prolonged QT syndrome.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Best overall response rate

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Ewing sarcomaExperimental Treatment2 Interventions

Participants have a diagnosis of Ewing sarcoma as molecularly defined by an EWSR1 fusion with an ETS-transcription factor family member including FLI1, ERG, ETV1, ETV4, and FEV

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine

2017

Completed Phase 3

~1920

0 / 7Eligibility 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

Common treatments for Ewing Sarcoma include chemotherapy agents like gemcitabine, which incorporates into DNA and disrupts replication, leading to cell death. Novel agents like LY2880070, though not fully detailed, likely target specific pathways critical for cancer cell survival. Other treatments, such as nab-paclitaxel, disrupt microtubule function, and PARP inhibitors like talazoparib enhance DNA damage. These mechanisms are vital for Ewing Sarcoma patients as they exploit the cancer's rapid cell division and genetic instability, potentially improving treatment efficacy and patient outcomes.

Vitamin E Phosphate Nucleoside Prodrugs: A Platform for Intracellular Delivery of Monophosphorylated Nucleosides.Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program.Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP).