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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04095221
Recruitment Status : Active, not recruiting
First Posted : September 19, 2019
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE September 17, 2019
First Posted Date  ICMJE September 19, 2019
Last Update Posted Date October 4, 2022
Actual Study Start Date  ICMJE September 17, 2019
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2019)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Desmoplastic Small Round Cell Tumor
  • Rhabdomyosarcoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Prexasertib
  • Drug: Irinotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 9, 2022)
21
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2019)
30
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04095221
Other Study ID Numbers  ICMJE 19-120
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Current Responsible Party Memorial Sloan Kettering Cancer Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Emily Slotkin, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP