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Anlotinib and Irinotecan for Ewing Sarcoma

Primary Purpose

Ewing's Tumor Metastatic

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Anlotinib
Irinotecan
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing's Tumor Metastatic focused on measuring Ewing Sarcoma, Anlotinib, Irinotecan, Refractory, Metastatic

Eligibility Criteria

5 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Peking University First Hospital
  • Peking University People's HospitalRecruiting
  • Peking University Shougang HospitalRecruiting
  • Peking University Third Hospital
  • People's Liberation Army General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Anlotinib and Irinotecan(phase 1b)

Anlotinib and Irinotecan(phase 2)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
January 24, 2018
Last Updated
February 13, 2019
Sponsor
Peking University People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03416517
Brief Title
Anlotinib and Irinotecan for Ewing Sarcoma
Official Title
Anlotinib and Irinotecan for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 22, 2018 (Actual)
Primary Completion Date
February 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing's Tumor Metastatic
Keywords
Ewing Sarcoma, Anlotinib, Irinotecan, Refractory, Metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Anlotinib and Irinotecan(phase 1b)
Arm Type
Experimental
Arm Description
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.
Arm Title
Anlotinib and Irinotecan(phase 2)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Anlotinib
Other Intervention Name(s)
AL3818
Intervention Description
Anlotinib 12 or 8 mg/d po D1-14 q3w
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
Irinotecan 20 or 15mg/m^2/d IV over 60 minutes on days 1-5 and 8-12, q3w
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) (phase 1b)
Description
evaluate the maximum tolerated dose (MTD) of combination therapy with irinotecan and anlotinib
Time Frame
12 months
Title
Object response rate(ORR) at 12 weeks (phase 2)
Description
complete response (CR) + partial response (PR) at 12 weeks
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Progression-free survival(PFS)
Description
Calculated from the date of treatment start until the time of disease progression or death, whichever comes first.
Time Frame
2 years
Title
Overall survival(OS)
Description
Calculated from the date of treatment start until last follow-up or death, whichever comes first.
Time Frame
2 years
Title
Adverse Effect
Description
Adverse effect measured by CTCAE v.4 (Common Terminology Criteria for Adverse Events)
Time Frame
2 years
Title
Quality of Life (QoL)
Description
Quality of Life measured by EORTC QLQ(quality of life questionnair) C-30 for adults or PedsQL3.0 for children.
Time Frame
2 years
Title
Pain management
Description
Pain management measured by Visual Analog Score for pain.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Guo, M.D, Ph.D
Phone
86 010 88326152
Email
bonetumor@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Guo, M.D, Ph.D
Organizational Affiliation
Peking University People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University First Hospital
City
Beijing
ZIP/Postal Code
100034
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chuan Mi, M.D
Facility Name
Peking University People's Hospital
City
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Xu, M.D.
Phone
86 010 66583761
Email
xujie_pkuph@sina.com
First Name & Middle Initial & Last Name & Degree
Xin Sun, M.D.
Phone
86 010 66583761
Email
xinsun1981@hotmail.com
Facility Name
Peking University Shougang Hospital
City
Beijing
ZIP/Postal Code
100144
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lu Xie, M.D.
Phone
86 010 57830370
Email
sweetdoctor@163.com
Facility Name
Peking University Third Hospital
City
Beijing
ZIP/Postal Code
100191
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liang Jiang, M.D
Email
jiangliang@bjmu.edu.cn
Facility Name
People's Liberation Army General Hospital
City
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenzhi Bi, M.D
Email
biwenzhi@sina.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34941047
Citation
Dong S, Sun K, Xie L, Xu J, Sun X, Ren T, Huang Y, Yang R, Tang X, Yang F, Gu J, Guo W. Quality of life and Q-TWiST were not adversely affected in Ewing sarcoma patients treated with combined anlotinib, irinotecan, and vincristine: (Peking University People's Hospital Ewing sarcoma trial-02, PKUPH-EWS-02). Medicine (Baltimore). 2021 Dec 23;100(51):e28078. doi: 10.1097/MD.0000000000028078.
Results Reference
derived

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Anlotinib and Irinotecan for Ewing Sarcoma

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