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

• ClinicalTrials.gov Identifier: NCT02044120
• Recruitment Status: Completed
• First Posted: January 23, 2014
• Last Update Posted: January 12, 2021
• Sponsor: Sarcoma Alliance for Research through Collaboration
• Information provided by (Responsible Party): Sarcoma Alliance for Research through Collaboration

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

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

Investigators

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

More Information

• Responsible Party: Sarcoma Alliance for Research through Collaboration
• ClinicalTrials.gov Identifier: NCT02044120
• Other Study ID Numbers: ESP1/SARC025
• First Posted: January 23, 2014
• Last Update Posted: January 12, 2021
• Last Verified: January 2021

Additional relevant MeSH terms:

Sarcoma; Sarcoma, Ewing; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Irinotecan; Temozolomide; Niraparib; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Poly(ADP-ribose) Polymerase Inhibitors