NCT03416517

Brief Summary

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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
47

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2018

Typical duration for phase_1

Geographic Reach
1 country

5 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 22, 2018

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

January 24, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 31, 2018

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2020

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

February 15, 2019

Status Verified

February 1, 2019

Enrollment Period

2 years

First QC Date

January 24, 2018

Last Update Submit

February 13, 2019

Conditions

Keywords

Ewing SarcomaAnlotinibIrinotecanRefractoryMetastatic

Outcome Measures

Primary Outcomes (2)

  • Maximum tolerated dose (MTD) (phase 1b)

    evaluate the maximum tolerated dose (MTD) of combination therapy with irinotecan and anlotinib

    12 months

  • Object response rate(ORR) at 12 weeks (phase 2)

    complete response (CR) + partial response (PR) at 12 weeks

    12 months

Secondary Outcomes (5)

  • Progression-free survival(PFS)

    2 years

  • Overall survival(OS)

    2 years

  • Adverse Effect

    2 years

  • Quality of Life (QoL)

    2 years

  • Pain management

    2 years

Study Arms (2)

Anlotinib and Irinotecan(phase 1b)

EXPERIMENTAL

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: AnlotinibDrug: Irinotecan

Anlotinib and Irinotecan(phase 2)

EXPERIMENTAL

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: AnlotinibDrug: Irinotecan

Interventions

Anlotinib 12 or 8 mg/d po D1-14 q3w

Also known as: AL3818
Anlotinib and Irinotecan(phase 1b)Anlotinib and Irinotecan(phase 2)

Irinotecan 20 or 15mg/m\^2/d IV over 60 minutes on days 1-5 and 8-12, q3w

Also known as: Camptosar
Anlotinib and Irinotecan(phase 1b)Anlotinib and Irinotecan(phase 2)

Eligibility Criteria

Age5 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Peking University First Hospital

Beijing, 100034, China

NOT YET RECRUITING

Peking University People's Hospital

Beijing, 100044, China

RECRUITING

Peking University Shougang Hospital

Beijing, 100144, China

RECRUITING

Peking University Third Hospital

Beijing, 100191, China

NOT YET RECRUITING

People's Liberation Army General Hospital

Beijing, 100853, China

NOT YET RECRUITING

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Sarcoma, EwingNeoplasm Metastasis

Interventions

anlotinibIrinotecan

Condition Hierarchy (Ancestors)

OsteosarcomaNeoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsSarcomaNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic Compounds

Study Officials

  • Wei Guo, M.D, Ph.D

    Peking University People's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Guo, M.D, Ph.D

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Musculoskeletal Tumor Center

Study Record Dates

First Submitted

January 24, 2018

First Posted

January 31, 2018

Study Start

January 22, 2018

Primary Completion

February 1, 2020

Study Completion

December 1, 2020

Last Updated

February 15, 2019

Record last verified: 2019-02

Locations