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

NCT04095221 | Completed Phase 1 FDA Drug

• 1 other identifier: 19-120
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Keywords

Prexasertib; Irinotecan; Temozolomide; 19-120

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Prexasertib and Irinotecan

EXPERIMENTAL

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; Drug: Irinotecan

Interventions

Prexasertib 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

Prexasertib and Irinotecan

Irinotecan DRUG

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

Prexasertib and Irinotecan

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy
• days must have elapsed after the last dose of anti-cancer agents not known to be myelosuppressive
• days must have elapsed after radiation therapy, and toxicity related to prior radiation therapy must be recovered to grade ≤ 1
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Desmoplastic Small Round Cell Tumor; Rhabdomyosarcoma

Interventions

prexasertib; Irinotecan

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Emily Slotkin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single institution study to determine the recommended phase 2 dose of prexasertib when given in combination with irinotecan and temozolomide. Patients with relapsed or refractory desmoplastic small round cell tumor or rhabdomyosarcoma of any subtype will receive prexasertib using the 3+3 dose-escalation schema.

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 19, 2019
• Study Start: September 17, 2019
• Primary Completion: February 18, 2025
• Study Completion: February 18, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)