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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04095221
Recruitment Status : Recruiting
First Posted : September 19, 2019
Last Update Posted : January 29, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Desmoplastic Small Round Cell Tumor Rhabdomyosarcoma Drug: Prexasertib Drug: Irinotecan Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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
Official Title: 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
Actual Study Start Date : September 17, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022


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




Primary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04095221


Contacts
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Contact: Emily Slotkin, MD 212-639-8856 slotkine@mskcc.org
Contact: Williiam Tap, MD 646-888-4163

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Emily Slotkin, MD    212-639-8856      
Contact: William Tap, MD    646-888-4163      
Principal Investigator: Emily Slotkin, MD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Emily Slotkin, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04095221    
Other Study ID Numbers: 19-120
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: January 29, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Prexasertib
Irinotecan
Temozolomide
19-120
Additional relevant MeSH terms:
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Rhabdomyosarcoma
Desmoplastic Small Round Cell Tumor
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents