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

A Phase I/II Dose Escalation/Dose Expansion Study of Prexasertib in Combination With Irinotecan in Patients With Relapsed or RefractoryDesmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Rhabdomyosarcoma; Desmoplastic Small Round Cell Tumor
• Intervention / Treatment: Drug: Prexasertib; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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; Drug: Irinotecan; 15 mg/m2 IV daily x 10 days in 21 day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recommended phase II does of Prexasertib	The RP2D is defined as the highest dose level associated with not more than 1 DLT out of 6 patients. A total of 5 dose levels are planned, including 2 back up levels. The DLT's will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The dose escalation will follow a 3+3 design.	1 year
response	will be evaluated in this study using the criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline, version 1.1 (Primary response criteria)54. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Emily Slotkin, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Temozolomide; Irinotecan; Prexasertib; 19-120
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Muscle Tissue; Myosarcoma; Rhabdomyosarcoma; Desmoplastic Small Round Cell Tumor; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Prexasertib
• Other Study ID Numbers: 19-120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No