A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

NCT ID: NCT04095221

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-17
• Study Completion Date: 2025-02-18

Brief Summary

The purpose of this study is to test whether the study drug prexasertib is a safe and effective treatment for people with DSRCT or RMS when given in combination with the standard drugs irinotecan and temozolomide. The study will test different doses of prexasertib in combination with irinotecan and temozolomide to find the highest dose of prexasertib that causes few or mild side effects in participants.

Conditions

Desmoplastic Small Round Cell Tumor; Rhabdomyosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prexasertib and Irinotecan

Patients will have extent of disease scans following every 2 cycles (every 6 weeks on dose levels 0-3, and every 8 weeks on dose level -1 (if required). Patients will be allowed to continue therapy as long as they do not experience dose-limiting toxicities or progression of disease.

Group Type: EXPERIMENTAL

Prexasertib

Intervention Type: DRUG

DOSE LEVELS FOR PATIENTS > 21 YEARS OF AGE, Dose Level -1, prexasertib 105 mg/ m2 once every 14 days in 28 day cycles Dose Level 0, 60 mg/m2 prexasertib once every 21 days Dose Level 1, (STARTING) 80 mg/m2 prexasertib once every 21 days Dose Level 2, 105 mg/m2 prexasertib once every 21 days Dose Level 3, 105 mg/m2 prexasertib once every 21 days

DOSE LEVELS FOR PATIENTS ≤ 21 YEARS OF AGE Dose Level -1, prexasertib 150 mg/ m2 once every 14 days in 28 day cycles, Dose Level 0, 60 mg/m2 prexasertib once every 21 days, Dose Level 1, (STARTING) 80 mg/m2 prexasertib once every 21 days, Dose Level 2, 150 mg/m2 prexasertib once every 21 days, Dose Level 3, 150 mg/m2 prexasertib once every 21 days

Irinotecan

Intervention Type: DRUG

15 mg/m2 IV daily x 10 days in 21 day cycles

Interventions

Prexasertib

DOSE LEVELS FOR PATIENTS > 21 YEARS OF AGE, Dose Level -1, prexasertib 105 mg/ m2 once every 14 days in 28 day cycles Dose Level 0, 60 mg/m2 prexasertib once every 21 days Dose Level 1, (STARTING) 80 mg/m2 prexasertib once every 21 days Dose Level 2, 105 mg/m2 prexasertib once every 21 days Dose Level 3, 105 mg/m2 prexasertib once every 21 days

DOSE LEVELS FOR PATIENTS ≤ 21 YEARS OF AGE Dose Level -1, prexasertib 150 mg/ m2 once every 14 days in 28 day cycles, Dose Level 0, 60 mg/m2 prexasertib once every 21 days, Dose Level 1, (STARTING) 80 mg/m2 prexasertib once every 21 days, Dose Level 2, 150 mg/m2 prexasertib once every 21 days, Dose Level 3, 150 mg/m2 prexasertib once every 21 days

Intervention Type: DRUG

Irinotecan

15 mg/m2 IV daily x 10 days in 21 day cycles

Intervention Type: DRUG

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
• Age: patients must be ≥12 months of age at the time of study enrollment
• Diagnosis: patients must have histologically documented locally advanced or metastatic desmoplastic small round cell tumor or rhabdomyosarcoma (confirmed at MSK)
• Therapeutic options: patient's current disease state must be one which has failed standard therapy and for which there is no known curative therapy
• Disease Status: patients must have measurable disease based on RECIST 1.1
• Performance level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
• Prior Therapy: patients may have had any number of prior therapies, but must have recovered from the acute toxic effects of all prior anti-cancer therapy (other than alopecia) as described below and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment

°patients who have previously received irinotecan and/or temozolomide will be allowed

• 21 days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy
• 7 days must have elapsed after the last dose of anti-cancer agents not known to be myelosuppressive
• 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/mm^3
• platelet count ≥ 100,000/ mm^3
• hemoglobin ≥ 8 g/dl
• Adequate renal function defined as:

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min/1.73m2 OR
• Serum creatinine based on age/gender derived from the Schwartz formula for estimating GFR53
• Adequate liver function defined as:

• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for age
• 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:

• echocardiogram with left ventricular ejection fraction (LVEF) >45%
• 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 participation

Exclusion Criteria

• Patients for whom the investigator deems that irinotecan and temozolomide are not appropriate are not eligible.
• Patients who have an uncontrolled infection are not eligible.
• Patients who are pregnant or breast feeding are not eligible.
• 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 are not eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with known hypersensitivity to irinotecan or its excipients are not eligible.

• Minimum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily Slotkin, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

19-120

Identifier Type: -

Identifier Source: org_study_id