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

NCT04095221

Description:

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.

Related Conditions:
  • Desmoplastic Small Round Cell Tumor
  • Rhabdomyosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma
  • Official Title: Phase I/II Dose Escalation/Dose Expansion Study of Prexasertib in Combination With Irinotecan and Temozolomide in Patients With Relapsed or Refractory Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

Clinical Trial IDs

  • ORG STUDY ID: 19-120
  • NCT ID: NCT04095221

Conditions

  • Desmoplastic Small Round Cell Tumor
  • Rhabdomyosarcoma

Interventions

DrugSynonymsArms
PrexasertibPrexasertib, Irinotecan, and Temozolomide
IrinotecanPrexasertib, Irinotecan, and Temozolomide
TemozolomidePrexasertib, Irinotecan, and Temozolomide

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Prexasertib, Irinotecan, and TemozolomideExperimentalPatients 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.
  • Prexasertib
  • Irinotecan
  • Temozolomide

Eligibility 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 ≤ 2.5 x upper limit of normal or ≤ 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 temozolomide or their excipients
             are not eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:recommended phase II does of Prexasertib
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Prexasertib
  • Irinotecan
  • Temozolomide
  • 19-120

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