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

Primary Purpose

Ewing Sarcoma, Ewing-Like Sarcoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LY2880070
Gemcitabine
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing Sarcoma focused on measuring Ewing Sarcoma, Ewing-Like Sarcoma, LY2880070, Gemcitabine, 21-428, Memorial Sloan Kettering Cancer Center

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion 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

Note: Any patient being enrolled into the pilot cohort will be reviewed with study pathologist, Dr. Cristina Antonescu, to ensure the categorization as Ewing-like sarcoma is appropriate.

  • 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 no more than 4 prior regimens (including frontline therapy) and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment

Note: Patients who have previously received gemcitabine will be allowed unless they had hypersensitivity or unacceptable toxicity attributed to gemcitabine

  • ≥ 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

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

Exclusion Criteria:

  • 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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ewing sarcoma

Arm Description

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

Outcomes

Primary Outcome Measures

Best overall response rate
The ORR will include complete response and partial response (CR+PR) as defined using RECIST 1.1 criteria.

Secondary Outcome Measures

Full Information

First Posted
March 2, 2022
Last Updated
October 5, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT05275426
Brief Title
A Study of LY2880070 and Gemcitabine in People With Ewing Sarcoma,Ewing-Like Sarcoma, and Desmoplastic Small Round Cell Tumor
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2022 (Actual)
Primary Completion Date
March 2, 2024 (Anticipated)
Study Completion Date
March 2, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing Sarcoma, Ewing-Like Sarcoma
Keywords
Ewing Sarcoma, Ewing-Like Sarcoma, LY2880070, Gemcitabine, 21-428, Memorial Sloan Kettering Cancer Center

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ewing sarcoma
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
LY2880070
Intervention Description
Patients will receive treatment in 21-day cycles with LY2880070 50 mg twice daily orally on days 2-6, 9-13, and 16-20
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Participants will receive treatment in 21-day cycles with gemcitabine 100 mg/m2 intravenously on days 1, 8 and optionally on day 15
Primary Outcome Measure Information:
Title
Best overall response rate
Description
The ORR will include complete response and partial response (CR+PR) as defined using RECIST 1.1 criteria.
Time Frame
6 months

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion 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 Note: Any patient being enrolled into the pilot cohort that does not have a CIC, BCOR- rearranged sarcoma, or desmoplastic small round cell tumor will be reviewed with study pathologist, Dr. Cristina Antonescu, to ensure the categorization as Ewing-like sarcoma is appropriate 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 Note: Patients who have previously received gemcitabine will be allowed unless they had hypersensitivity or unacceptable toxicity attributed to gemcitabine ≥ 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 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emily Slotkin, MD
Phone
833-675-5437
Email
slotkine@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Viswatej Avutu, MD
Phone
646-888-6860
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
833-675-5437

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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