Irinotecan and Temozolomide for Ewing Sarcoma

Irinotecan and Temozolomide for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy

The investigators explored the activity of vincristine and irinotecan combined with temozolomide (VIT) in patients with relapsed and metastatic Ewing Sarcoma.

Study Overview

• Status: Recruiting
• Conditions: Ewing Sarcoma
• Intervention / Treatment: Drug: Vincristine; Drug: Temozolomide

Detailed Description

After standard multimodal therapy, the prognosis of relapsed and metastatic Ewing Sarcoma is dismal and unchanged over the last decades. The anti-tumor activity of VIT was demonstrated by several studies in the past. However, the detailed schedule of VIT was not decided. Thus, the investigators explored the activity of 5-d shorter schedule of VIT and 5-d x2w longer schedule of VIT in patients with relapsed and metastatic Ewing Sarcoma after the failure of first-line chemotherapy with doxorubicin, vincristine, cyclophosphamide, ifosphamide and etoposide.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Xu, M.D.; Phone Number: 86-15901040835; Email: xujie_pkuph@sina.com
• Study Contact Backup: Name: Lu Xie, M.D.; Phone Number: 86-13401044719; Email: sweetdoctor@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University People's Hospital
      • Contact: Jie Xu; Phone Number: 86 15901040835; Email: xujie_pkuph@sina.com
      • Principal Investigator: Wei Guo, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 fluorescence in situ hybridization (FISH) or real-time polymerase chain reaction (RT-PCT).
• Recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator.
• Prior treatment consisted of standard Ewing Sarcoma chemotherapy agents including doxorubicin, vincristine, cyclophosphamide, ifosfamide and etoposide; metastatic relapsed and unresectable progressive disease (PD);
• Life expectancy of ≥ 3 months.
• Eastern Cooperative Oncology Group performance status 0-1
• Measurable disease on CT or MRI by RECIST 1.1.
• Adequate organ function.
• 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.
• 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 corrected QT interval(QTc) > 480 msec.
• 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) or any of its components, and irinotecan or any of its components.
• 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.
• Inability to swallow capsules.
• Other clinically significant malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.
• Known persistent (> 4 weeks) ≥ Grade 2 neutropenia, ≥ Grade 2 thrombocytopenia or > Grade 3 anemia from prior cancer therapy.
• Other kinds of malignant tumors at the same time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5d VIT (irinotecan, temozolomide and vincristine); Irinotecan 50mg/m2/d IV over 60 minutes on days 1-5. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.	Drug: Vincristine; vincristine 1.5mg/m2 iv D1,D8; Other Names: VCR; Drug: Temozolomide; Temozolomide 100mg/m2/d iv on days 1-5.; Other Names: Temodar
Active Comparator: 5d x 2 VIT (irinotecan, temozolomide and vincristine); Irinotecan 20mg/m2/d IV over 60 minutes on days 1-5 and 8-12. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.	Drug: Vincristine; vincristine 1.5mg/m2 iv D1,D8; Other Names: VCR; Drug: Temozolomide; Temozolomide 100mg/m2/d iv on days 1-5.; Other Names: Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Object response rate(ORR) at 12 weeks	complete response (CR) + partial response (PR) at 12 weeks	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	Calculated from the date of treatment start until the time of disease progression or death, whichever comes first.	2 years
Overall survival(OS)	Calculated from the date of treatment start until last follow-up or death, whichever comes first.	2 years
Duration of response(DOR)	Duration of response is calculated from the day of first response assessment until either progression/death (event) or last day of follow-up (censored).	2 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Wei Guo, Ph.D, M.D., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Anticipated): November 28, 2022
• Study Completion (Anticipated): February 28, 2025

Study Registration Dates

• First Submitted: November 26, 2017
• First Submitted That Met QC Criteria: November 27, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Temozolomide; Irinotecan; Ewing Sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Temozolomide; Vincristine
• Other Study ID Numbers: PKUPH-EWS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No