Anlotinib and Irinotecan for Ewing Sarcoma

February 13, 2019 updated by: GUO WEI, Peking University People's Hospital

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

The investigators explored the activity of anlotinib combined with irinotecan in patients with relapsed and metastatic Ewing Sarcoma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

After standard multimodal therapy, the prognosis of relapsed and metastatic Ewing Sarcoma is dismal and unchanged over the last decades.Thus, the investigators explored the activity of anlotinib combined with irinotecan 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)

47

Phase

  • Phase 2
  • 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 Contact

Study Locations

  • China
      • Beijing, China, 100191
      • Beijing, China, 100034
        • Not yet recruiting
        • Peking University First Hospital
        • Contact:
          • Chuan Mi, M.D
      • Beijing, China, 100044
        • Recruiting
        • Peking University People's Hospital
        • Contact:
        • Contact:
      • Beijing, China, 100144
        • Recruiting
        • Peking University Shougang Hospital
        • Contact:
      • Beijing, China, 100853
        • Not yet recruiting
        • People's Liberation Army General Hospital
        • Contact:

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

5 years to 65 years (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.
  • Prior treatment consisted of anlotinib, any other antiangiogenic TKIs, or irinotecan.
  • Patients with baseline corrected QT interval(QTc) > 480 msec.
  • Known hypersensitivity reaction to anlotinib 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 or water.
  • 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

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: Anlotinib and Irinotecan(phase 1b)
Anlotinib 12 or 8 mg/d PO on days 1-14 q3w. Irinotecan 20 or 15mg/m^2/d over 60 minutes on days 1-5 and 8-12 q3w. Vincristine 1.4mg/m^2/d IV on days 1,8 q3w. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Drug: Anlotinib
Anlotinib 12 or 8 mg/d po D1-14 q3w
Other Names:
  • AL3818
Drug: Irinotecan
Irinotecan 20 or 15mg/m^2/d IV over 60 minutes on days 1-5 and 8-12, q3w
Other Names:
  • Camptosar
Experimental: Anlotinib and Irinotecan(phase 2)
Anlotinib 12 or 8 mg/d PO on days 1-14 q3w. Irinotecan 20 or 15 mg/m^2/d IV over 60 minutes on days 1-5 and 8-12 q3w. The final dose of anlotinib and irinotecan depends on the result from previous phase Ib study. Vincristine 1.4mg/m^2/d IV on days 1,8 q3w. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Drug: Anlotinib
Anlotinib 12 or 8 mg/d po D1-14 q3w
Other Names:
  • AL3818
Drug: Irinotecan
Irinotecan 20 or 15mg/m^2/d IV over 60 minutes on days 1-5 and 8-12, q3w
Other Names:
  • Camptosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) (phase 1b)
Time Frame: 12 months
evaluate the maximum tolerated dose (MTD) of combination therapy with irinotecan and anlotinib
12 months
Object response rate(ORR) at 12 weeks (phase 2)
Time Frame: 12 months
complete response (CR) + partial response (PR) at 12 weeks
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival(PFS)
Time Frame: 2 years
Calculated from the date of treatment start until the time of disease progression or death, whichever comes first.
2 years
Overall survival(OS)
Time Frame: 2 years
Calculated from the date of treatment start until last follow-up or death, whichever comes first.
2 years
Adverse Effect
Time Frame: 2 years
Adverse effect measured by CTCAE v.4 (Common Terminology Criteria for Adverse Events)
2 years
Quality of Life (QoL)
Time Frame: 2 years
Quality of Life measured by EORTC QLQ(quality of life questionnair) C-30 for adults or PedsQL3.0 for children.
2 years
Pain management
Time Frame: 2 years
Pain management measured by Visual Analog Score for pain.
2 years

Collaborators and Investigators

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

Sponsor

Peking University People's Hospital

Investigators

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

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 (Actual)

January 22, 2018

Primary Completion (Anticipated)

February 1, 2020

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

January 24, 2018

First Submitted That Met QC Criteria

January 29, 2018

First Posted (Actual)

January 31, 2018

Study Record Updates

Last Update Posted (Actual)

February 15, 2019

Last Update Submitted That Met QC Criteria

February 13, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PKUPH-EWS-02

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

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.

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