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

January 8, 2021 updated by: Sarcoma Alliance for Research through Collaboration

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, W1T 7HA
        • University College London Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital of Los Angeles
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • University of Michigan
    • Washington
      • Seattle, Washington, United States, 98101
        • Seattle's Children Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Approximately 24 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sarcoma Alliance for Research through Collaboration

Investigators

  • Principal Investigator: Rashmi Chugh, MD, University of Michigan
  • Principal Investigator: Sandra Strauss, MBBS, PhD, University College London, Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

January 1, 2021

Study Completion (Actual)

January 1, 2021

Study Registration Dates

First Submitted

January 21, 2014

First Submitted That Met QC Criteria

January 21, 2014

First Posted (Estimate)

January 23, 2014

Study Record Updates

Last Update Posted (Actual)

January 12, 2021

Last Update Submitted That Met QC Criteria

January 8, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESP1/SARC025

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ewing Sarcoma

Clinical Trials on Temozolomide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe