COMPLETED

A Study of LY2880070 and Gemcitabine in People With Ewing Sarcoma,Ewing-Like Sarcoma, and Desmoplastic Small Round Cell Tumor

Conditions

Ewing Sarcoma Ewing-Like Sarcoma LY2880070 Gemcitabine 21-428 Memorial Sloan Kettering Cancer Center

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to find out whether LY2880070 combined with the chemotherapy drug gemcitabine is an effective treatment for Ewing sarcoma or Ewing-like sarcoma.

Official Title

A Phase II Study of Oral CHK1 Inhibitor LY2880070 in Combination With Low-Dose Gemcitabine in Patients With Relapsed or Refractory Ewing Sarcoma, Ewing-like Sarcoma, and Desmoplastic Small Round Cell Tumor

Quick Facts

Study Start:2022-03-02

Study Completion:2025-08-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:COMPLETED

Study ID

NCT05275426

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Consent/Assent: all patients and/or their parents or legally authorized representatives must sign written informed consent; assent, when appropriate, will be obtained according to institutional guidelines * Weight/Age: patients must be ≥40 kg at the time of study enrollment, but may be of any age * Diagnosis: Patients must have histologically documented locally advanced or metastatic disease confirmed at MSK as follows: * Main cohort: Ewing sarcoma as molecularly defined by an EWSR1 fusion with an ETS-transcription factor family member including FLI1, ERG, ETV1, ETV4, and FEV * Pilot cohort: Ewing-like sarcomas including CIC-rearranged sarcoma, BCOR-rearranged sarcoma, and sarcomas with a rearrangement between EWSR1 and a non-ETS family gene or desmoplastic small round cell tumor as molecularly defined by an EWSR1-WT1 fusion * Patients must be able to swallow capsules * Therapeutic options: patient's current disease state must be one which has failed standard cytotoxic chemotherapy including cyclophosphamide/doxorubicin/vincristine and ifosfamide/etoposide * Disease Status: patients must have measurable disease based on RECIST 1.1 * Performance level: Karnofsky ≥70% for patients \>16 years of age and Lansky ≥70 for patients ≤16 years of age * Prior Therapy: patients may have had any number of regimens and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment * ≥ 21 days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy and patients must have recovered from the acute toxic effects of these agents (other than alopecia) * ≥ 14 days must have elapsed after radiation therapy, and toxicity related to prior radiation therapy must be recovered to grade ≤ 1 * ≥ 21 days must have elapsed after the last dose of antibody therapy, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1 * 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	* Patients for whom the investigator deems that gemcitabine is not appropriate * Patients who have an uncontrolled infection * Central Nervous System (CNS) Metastases * Patients who have symptomatic central nervous system (CNS) metastases. Note: patients with treated and asymptomatic CNS metastases are eligible. * Patients with CNS metastases requiring corticosteroids for management * If the treatment of CNS disease requires anticonvulsants, the dose must have been stable for ≥ 4 weeks. * Patients who are pregnant or breast feeding * 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 * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study * Patients with known hypersensitivity to gemcitabine

Inclusion Criteria

Exclusion Criteria

* Consent/Assent: all patients and/or their parents or legally authorized representatives must sign written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
* Weight/Age: patients must be ≥40 kg at the time of study enrollment, but may be of any age
* Diagnosis: Patients must have histologically documented locally advanced or metastatic disease confirmed at MSK as follows:
* Main cohort: Ewing sarcoma as molecularly defined by an EWSR1 fusion with an ETS-transcription factor family member including FLI1, ERG, ETV1, ETV4, and FEV
* Pilot cohort: Ewing-like sarcomas including CIC-rearranged sarcoma, BCOR-rearranged sarcoma, and sarcomas with a rearrangement between EWSR1 and a non-ETS family gene or desmoplastic small round cell tumor as molecularly defined by an EWSR1-WT1 fusion
* Patients must be able to swallow capsules
* Therapeutic options: patient's current disease state must be one which has failed standard cytotoxic chemotherapy including cyclophosphamide/doxorubicin/vincristine and ifosfamide/etoposide
* Disease Status: patients must have measurable disease based on RECIST 1.1
* Performance level: Karnofsky ≥70% for patients \>16 years of age and Lansky ≥70 for patients ≤16 years of age
* Prior Therapy: patients may have had any number of regimens and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment
* ≥ 21 days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy and patients must have recovered from the acute toxic effects of these agents (other than alopecia)
* ≥ 14 days must have elapsed after radiation therapy, and toxicity related to prior radiation therapy must be recovered to grade ≤ 1
* ≥ 21 days must have elapsed after the last dose of antibody therapy, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
* 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

* Patients for whom the investigator deems that gemcitabine is not appropriate
* Patients who have an uncontrolled infection
* Central Nervous System (CNS) Metastases
* Patients who have symptomatic central nervous system (CNS) metastases. Note: patients with treated and asymptomatic CNS metastases are eligible.
* Patients with CNS metastases requiring corticosteroids for management
* If the treatment of CNS disease requires anticonvulsants, the dose must have been stable for ≥ 4 weeks.
* Patients who are pregnant or breast feeding
* 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
* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
* Patients with known hypersensitivity to gemcitabine

Contacts and Locations

Principal Investigator

Emily Slotkin, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Emily Slotkin, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-02

Study Completion Date2025-08-11

Study Record Updates

Study Start Date2022-03-02

Study Completion Date2025-08-11

Terms related to this study

Keywords Provided by Researchers

Ewing Sarcoma
Ewing-Like Sarcoma
LY2880070
Gemcitabine
21-428
Memorial Sloan Kettering Cancer Center

Additional Relevant MeSH Terms

Ewing Sarcoma
Ewing-Like Sarcoma