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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 : Completed
First Posted : January 23, 2014
Last Update Posted : January 12, 2021
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

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.

Condition or disease Intervention/treatment Phase
Ewing Sarcoma Drug: niraparib Drug: Temozolomide Drug: Irinotecan Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2014
Actual Primary Completion Date : January 2021
Actual Study Completion Date : January 2021

Arm Intervention/treatment
Experimental: niraparib and temozolomide
Niraparib (capsule) and temozolomide (capsule) will be taken together.
Drug: niraparib
Drug: Temozolomide
Experimental: niraparib and irinotecan
Niraparib will be taken orally and irinotecan will be administered intravenously.
Drug: niraparib
Drug: Irinotecan
Experimental: niraparib, irinotecan and temozolomide
Niraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.
Drug: niraparib
Drug: Temozolomide
Drug: Irinotecan

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Tumor response rate [ Time Frame: Approximately 24 months ]
    The percentage of patients whose tumor shrinks or disappears after treatment

  2. Progression-free survival [ Time Frame: Month 4 and 6 ]
    The time from starting treatment until disease progression

  3. Duration of response [ Time Frame: Approximately 24 months ]
    The time from tumor response to disease progression

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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): NCT02044120

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United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48106
United States, Washington
Seattle's Children Cancer Center
Seattle, Washington, United States, 98101
United Kingdom
University College London Hospital
London, United Kingdom, W1T 7HA
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
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Principal Investigator: Rashmi Chugh, MD University of Michigan
Principal Investigator: Sandra Strauss, MBBS, PhD University College London, Cancer Institute
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier: NCT02044120    
Other Study ID Numbers: ESP1/SARC025
First Posted: January 23, 2014    Key Record Dates
Last Update Posted: January 12, 2021
Last Verified: January 2021
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Poly(ADP-ribose) Polymerase Inhibitors