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

NCT02044120 | Completed Phase 1

• 1 other identifier: ESP1/SARC025
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 5

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.

Conditions

Ewing Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Tumor response rate

  Approximately 24 months

• Progression-free survival

  Month 4 and 6

• Duration of response

  Approximately 24 months

Study Arms (3)

niraparib and temozolomide

EXPERIMENTAL

Niraparib (capsule) and temozolomide (capsule) will be taken together.

Drug: niraparib; Drug: Temozolomide

niraparib and irinotecan

EXPERIMENTAL

Niraparib will be taken orally and irinotecan will be administered intravenously.

Drug: niraparib; Drug: Irinotecan

niraparib, irinotecan and temozolomide

EXPERIMENTAL

Niraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.

Drug: niraparib; Drug: Temozolomide; Drug: Irinotecan

Interventions

niraparib DRUG

niraparib and irinotecan; niraparib and temozolomide; niraparib, irinotecan and temozolomide

Temozolomide DRUG

niraparib and temozolomide; niraparib, irinotecan and temozolomide

Irinotecan DRUG

niraparib and irinotecan; niraparib, irinotecan and temozolomide

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead

Study Sites (5)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

University of Michigan

Ann Arbor, Michigan, 48106, United States

Location

Seattle's Children Cancer Center

Seattle, Washington, 98101, United States

Location

University College London Hospital

London, W1T 7HA, United Kingdom

Location

Related Publications (1)

• Chugh R, Ballman KV, Helman LJ, Patel S, Whelan JS, Widemann B, Lu Y, Hawkins DS, Mascarenhas L, Glod JW, Ji J, Zhang Y, Reinke D, Strauss SJ. SARC025 arms 1 and 2: A phase 1 study of the poly(ADP-ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma. Cancer. 2021 Apr 15;127(8):1301-1310. doi: 10.1002/cncr.33349. Epub 2020 Dec 8.

  PMID: 33289920 DERIVED

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

niraparib; Temozolomide; Irinotecan

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Rashmi Chugh, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Sandra Strauss, MBBS, PhD

  University College London, Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 23, 2014
• Study Start: May 1, 2014
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: January 12, 2021

Record last verified: 2021-01

Locations

GB (1); US (4)