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Prexasertib and Irinotecan for the Treatment of Relapsed or Refractory Desmoplastic Small Round Cell Tumor or Rhabdomyosarcoma

Trial Status: Active

This phase I / II trial studies the best dose, the side effects, and how well prexasertib and irinotecan work in treating patients with desmoplastic small cell tumor or rhabdomysosarcoma that has come back (relapsed) or does not respond to treatment (refractory). Prexasertib is a type of medication called a checkpoint kinase inhibitor. It works by stopping cancer cells from repairing damage to themselves and their deoxyribonucleic acid (DNA) (genes), which may lead to death of cancer cells. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The purpose of this study is to test whether prexasertib is a safe and effective treatment for patients with desmoplastic small round cell tumor or rhabdomyosarcoma when given with irinotecan.

Inclusion Criteria

  • 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
  • Patients must have histologically documented locally advanced or metastatic desmoplastic small round cell tumor or rhabdomyosarcoma (confirmed at Memorial Sloan Kettering [MSK])
  • Patient’s current disease state must be one which has failed standard therapy and for which there is no known curative therapy
  • Patients must have measurable disease based on RECIST 1.1
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
  • 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
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/ mm^3
  • Hemoglobin >= 8 g/dl
  • Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows: * Age (years): Maximum serum creatinine (mg/dL) * 1 to < 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) * 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) * 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female) * 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) * 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female) * >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal for age
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 5 x upper limit of normal for patients with liver metastases
  • Serum albumin >= 2.5 g/dl
  • Echocardiogram with left ventricular ejection fraction (LVEF) > 45%
  • Corrected QT (QTc) < 470 ms on screening 12 lead electrocardiogram
  • 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

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Emily Kanaya Slotkin
Phone: 212-639-8856

PRIMARY OBJECTIVES:

I. To determine the dose limiting toxicities and recommended phase 2 dose of prexasertib in combination with irinotecan.

II. To evaluate the efficacy of prexasertib in combination with irinotecan as assessed by investigator assessed best overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with relapsed or refractory desmoplastic small round cell tumor.

SECONDARY OBJECTIVES:

I. To estimate the efficacy of prexasertib in combination with irinotecan in patients with relapsed or refractory rhabdomyosarcoma.

II. To assess the time to progression and overall survival in patients with relapsed or refractory desmoplastic small round cell tumor or rhabdomyosarcoma treated with prexasertib alone and of prexasertib in combination with irinotecan.

CORRELATIVE OBJECTIVES:

I. To correlate tumor genomic profiling data with response in patients with relapsed or refractory desmoplastic small round cell tumor or rhabdomyosarcoma treated with prexasertib in combination with irinotecan.

II. To determine the baseline characteristics and potential effect of prexasertib on proposed biomarkers in pre- and post- treatment biopsies.

III. To correlate circulating-tumor DNA (ctDNA) analysis of plasma samples with radiographic findings in patients with relapsed or refractory desmoplastic small round cell tumor or rhabdomyosarcoma treated with prexasertib in combination with irinotecan at baseline and throughout protocol therapy.

OUTLINE: This is a dose escalation study of prexasertib. Patients are assigned to 1 of 3 arms.

ARM I (DOSE LEVEL 1, AND 2): Patients receive irinotecan IV over 60 minutes daily on days 1-10, and prexasertib IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (DOSE LEVEL 2A): Patients receive irinotecan IV over 60 minutes daily on days 1-5, and prexasertib IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM III (DOSE LEVEL 3): Patients receive irinotecan IV over 60 minutes daily on days 1-3 and 15-17, and prexasertib IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and then every 3 or 6 months.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Emily Kanaya Slotkin

  • Primary ID 19-120
  • Secondary IDs NCI-2019-06602
  • Clinicaltrials.gov ID NCT04095221