Clinical Trials /

ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide and/or Irinotecan Patients With Previously Treated, Incurable Ewing Sarcoma

NCT02044120

Description:

The purpose of this study is to define the dose-limiting toxicities and maximum tolerated dose of the poly ADP-ribose polymerase inhibitor niraparib and escalating doses of temozolomide and/or irinotecan in patients with pre-treated incurable Ewing sarcoma.

Related Conditions:
  • Ewing Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide and/or Irinotecan or Irinotecan and Temozolomide in Patients With Previously Treated, Incurable Ewing Sarcoma
  • Official Title: ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide and/or Irinotecan or Irinotecan and Temozolomide in Patients With Previously Treated,Incurable Ewing Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: ESP1/SARC025
  • NCT ID: NCT02044120

Conditions

  • Ewing Sarcoma

Interventions

DrugSynonymsArms
niraparibniraparib and temozolomide
Temozolomideniraparib and temozolomide
Irinotecanniraparib and irinotecan

Purpose

The purpose of this study is to define the dose-limiting toxicities and maximum tolerated dose of the poly ADP-ribose polymerase inhibitor niraparib and escalating doses of temozolomide or irinotecan or irinotecan and temozolomide in patients with pre-treated incurable Ewing sarcoma.

Trial Arms

NameTypeDescriptionInterventions
niraparib and temozolomideExperimentalNiraparib (capsule) and temozolomide (capsule) will be taken together.
  • niraparib
  • Temozolomide
niraparib and irinotecanExperimentalNiraparib will be taken orally and irinotecan will be administered intravenously.
  • niraparib
  • Irinotecan
niraparib, irinotecan and temozolomideExperimentalNiraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.
  • niraparib
  • Temozolomide
  • Irinotecan

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed Ewing sarcoma

          -  Evidence of Ewing sarcoma translocation by FISH or RT-PCR.

          -  Must be willing to undergo tumor biopsy at study entry for biologic correlates.

          -  If patient > 18 years, must be willing to undergo on-treatment tumor biopsy unless
             medically contra-indicated

          -  Recurrent or refractory tumors with no known curative treatment options according to
             the judgment of the investigator.

          -  Age ≥ 13 years.

          -  Life expectancy of ≥ 3 months.

          -  ECOG performance status 0-2.

          -  Measurable disease on CT or MRI by RECIST 1.1.

          -  Adequate organ function

          -  Patients must have received as a minimum a first line chemotherapy regimen consisting
             of at least 2 of the following agents: doxorubicin, cyclophosphamide, ifosfamide,
             etoposide.

          -  Time elapsed from previous therapy must be ≥ 3 weeks for systemic therapy, ≥ 2 weeks
             for radiation therapy or major surgery.

          -  Patients who have undergone autologous hematopoietic stem cell transplantation are
             eligible once they have recovered from all toxicities from therapy

          -  Patients who have received allogeneic hematopoietic stem cell transplantation will be
             eligible 6 months after the procedure provided there is no evidence of active
             graft-versus-host disease and immunosuppressive treatment has been discontinued for at
             least 30 days.

          -  Patients with central nervous system disease are eligible for enrollment if they have
             received prior radiotherapy or surgery to sites of central nervous system metastatic
             disease, have been off glucocorticoids for at least 4 weeks, have no overt evidence of
             neurological deficit and are ≥ 6 weeks from completion of brain irradiation.

          -  Patients or their legal representative (if the patient is < 18 years old) must be able
             to read, understand and provide written informed consent to participate in the trial.

          -  Females of childbearing potential as well as males and their partners must agree to
             use an effective form of contraception during the study and for 6 months following the
             last dose of study medication.

        Exclusion Criteria:

          -  Clinically significant unrelated illness which would, in the judgment of the treating
             physician, compromise the patient's ability to tolerate the investigational agent or
             be likely to interfere with the study procedures or results.

          -  Patients with baseline QTc > 480 msec.

          -  Inability to swallow capsules.

          -  Known hypersensitivity to any of the components of niraparib or prior hypersensitivity
             reactions to that class of drugs.

          -  Known hypersensitivity reaction to temozolomide or any of its components, or
             dacarbazine (DTIC) if enrolled on ARM 1 or irinotecan or any of its components if
             enrolled on ARM 2

          -  Concomitant use of any other investigational or anticancer agent(s).

          -  Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy
             (post menarche and not post-menopausal, defined as over 12 months since final
             menstrual period) must have a negative pregnancy test within 7 days prior to first
             dose.

          -  Other clinically significant malignant disease diagnosed within the previous 5 years,
             excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.

          -  Active central nervous system disease.

          -  Known history of MDS or AML

          -  Known persistent (> 4 weeks) ≥ Grade 2 neutropenia, ≥ Grade 2 thrombocytopenia or >
             Grade 3 anemia from prior cancer therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:13 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity and maximum tolerated dose
Time Frame:Approximately 24 months
Safety Issue:
Description:Dose limiting toxicity describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. The maximum tolerated dose is the highest dose of a drug or treatment that does not cause unacceptable side effects.

Secondary Outcome Measures

Measure:Tumor response rate
Time Frame:Approximately 24 months
Safety Issue:
Description:The percentage of patients whose tumor shrinks or disappears after treatment
Measure:Progression-free survival
Time Frame:Month 4 and 6
Safety Issue:
Description:The time from starting treatment until disease progression
Measure:Duration of response
Time Frame:Approximately 24 months
Safety Issue:
Description:The time from tumor response to disease progression

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarcoma Alliance for Research through Collaboration

Last Updated