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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

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ClinicalTrials.gov Identifier: NCT02044120
Recruitment Status : Recruiting
First Posted : January 23, 2014
Last Update Posted : February 11, 2019
Sponsor:
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

Tracking Information
First Submitted Date  ICMJE January 21, 2014
First Posted Date  ICMJE January 23, 2014
Last Update Posted Date February 11, 2019
Study Start Date  ICMJE May 2014
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2014)
Dose-limiting toxicity and maximum tolerated dose [ Time Frame: Approximately 24 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02044120 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
  • Tumor response rate [ Time Frame: Approximately 24 months ]
    The percentage of patients whose tumor shrinks or disappears after treatment
  • Progression-free survival [ Time Frame: Month 4 and 6 ]
    The time from starting treatment until disease progression
  • Duration of response [ Time Frame: Approximately 24 months ]
    The time from tumor response to disease progression
Original Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2014)
  • Tumor response rate of patients treated with niraparib and temozolomide. [ Time Frame: Approximately 24 months ]
    The percentage of patients whose tumor shrinks or disappears after treatment with niraparib and temozolomide.
  • Progression-free survival at 4 and 6 months of patients treated with niraparib and temozolomide [ Time Frame: Month 4 and 6 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide and/or Irinotecan in Patients With Previously Treated,Incurable Ewing Sarcoma
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ewing Sarcoma
Intervention  ICMJE
  • Drug: niraparib
  • Drug: Temozolomide
  • Drug: Irinotecan
Study Arms  ICMJE
  • Experimental: niraparib and temozolomide
    Niraparib (capsule) and temozolomide (capsule) will be taken together.
    Interventions:
    • Drug: niraparib
    • Drug: Temozolomide
  • Experimental: niraparib and irinotecan
    Niraparib will be taken orally and irinotecan will be administered intravenously.
    Interventions:
    • Drug: niraparib
    • Drug: Irinotecan
  • Experimental: niraparib, irinotecan and temozolomide
    Niraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.
    Interventions:
    • Drug: niraparib
    • Drug: Temozolomide
    • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 4, 2018)
41
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2014)
30
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: SARC Office 734-930-7600 sarc@sarctrials.org
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02044120
Other Study ID Numbers  ICMJE ESP1/SARC025
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sarcoma Alliance for Research through Collaboration
Study Sponsor  ICMJE Sarcoma Alliance for Research through Collaboration
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rashmi Chugh, MD University of Michigan
Principal Investigator: Sandra Strauss, MBBS, PhD University College London, Cancer Institute
PRS Account Sarcoma Alliance for Research through Collaboration
Verification Date February 2019

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