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

Ewing Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02044120
• Other study ID #: ESP1/SARC025
• Status: Completed
• Phase: Phase 1
• Start date: May 2014
• Est. completion date: January 2021

Study information

• Verified date: January 2021
• Source: Sarcoma Alliance for Research through Collaboration
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ewing Sarcoma
• Sarcoma
• Sarcoma, Ewing

Intervention

Drug:
• niraparib

• Temozolomide

• Irinotecan

Locations

Country	Name	City	State
United Kingdom	University College London Hospital	London
United States	University of Michigan	Ann Arbor	Michigan
United States	National Cancer Institute	Bethesda	Maryland
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Seattle's Children Cancer Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sarcoma Alliance for Research through Collaboration

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity and maximum tolerated dose	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	Tumor response rate	The percentage of patients whose tumor shrinks or disappears after treatment	Approximately 24 months
Secondary	Progression-free survival	The time from starting treatment until disease progression	Month 4 and 6
Secondary	Duration of response	The time from tumor response to disease progression	Approximately 24 months