A Study of LY2880070 and Gemcitabine in People With Ewing Sarcoma or Ewing-Like Sarcoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05275426

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Ewing Sarcoma Ewing-Like Sarcoma	Drug: LY2880070 Drug: Gemcitabine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 2, 2022

Anticipated Primary Completion Date :

Mar 2, 2024

Anticipated Study Completion Date :

Mar 2, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ewing sarcoma 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	Drug: LY2880070 Patients will receive treatment in 21-day cycles with LY2880070 50 mg twice daily orally on days 2-6, 9-13, and 16-20 Drug: Gemcitabine Participants will receive treatment in 21-day cycles with gemcitabine 100 mg/m2 intravenously on days 1, 8 and optionally on day 15

Arm

Intervention/Treatment

Experimental: Ewing sarcoma

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

Drug: LY2880070

Patients will receive treatment in 21-day cycles with LY2880070 50 mg twice daily orally on days 2-6, 9-13, and 16-20

Drug: Gemcitabine

Participants will receive treatment in 21-day cycles with gemcitabine 100 mg/m2 intravenously on days 1, 8 and optionally on day 15

Outcome Measures

Primary Outcome Measures

Best overall response rate [6 months]
The ORR will include complete response and partial response (CR+PR) as defined using RECIST 1.1 criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts 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