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
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- recommended phase II does of Prexasertib
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Months to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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.
Arms & Interventions
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.
Intervention: Prexasertib (Drug)
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.
Intervention: Irinotecan (Drug)
Outcomes
Primary Outcomes
recommended phase II does of Prexasertib
Time Frame: 1 year
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.
response
Time Frame: 2 years
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.
Secondary Outcomes
No secondary outcomes reported