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Anlotinib and Irinotecan for Ewing Sarcoma

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ClinicalTrials.gov Identifier: NCT03416517
Recruitment Status : Unknown
Verified February 2019 by GUO WEI, Peking University People's Hospital.
Recruitment status was:  Recruiting
First Posted : January 31, 2018
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
GUO WEI, Peking University People's Hospital

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

Condition or disease Intervention/treatment Phase
Ewing's Tumor Metastatic Drug: Anlotinib Drug: Irinotecan Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Anlotinib and Irinotecan for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy
Actual Study Start Date : January 22, 2018
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : December 2020


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 Name: AL3818

Drug: Irinotecan
Irinotecan 20 or 15mg/m^2/d IV over 60 minutes on days 1-5 and 8-12, q3w
Other Name: 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 Name: AL3818

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




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) (phase 1b) [ Time Frame: 12 months ]
    evaluate the maximum tolerated dose (MTD) of combination therapy with irinotecan and anlotinib

  2. Object response rate(ORR) at 12 weeks (phase 2) [ Time Frame: 12 months ]
    complete response (CR) + partial response (PR) at 12 weeks


Secondary Outcome Measures :
  1. 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. Overall survival(OS) [ Time Frame: 2 years ]
    Calculated from the date of treatment start until last follow-up or death, whichever comes first.

  3. Adverse Effect [ Time Frame: 2 years ]
    Adverse effect measured by CTCAE v.4 (Common Terminology Criteria for Adverse Events)

  4. 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.

  5. Pain management [ Time Frame: 2 years ]
    Pain management measured by Visual Analog Score for pain.



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Ages Eligible for Study:   5 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03416517


Contacts
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Contact: Wei Guo, M.D, Ph.D 86 010 88326152 bonetumor@163.com

Locations
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China
Peking University First Hospital Not yet recruiting
Beijing, China, 100034
Contact: Chuan Mi, M.D         
Peking University People's Hospital Recruiting
Beijing, China, 100044
Contact: Jie Xu, M.D.    86 010 66583761    xujie_pkuph@sina.com   
Contact: Xin Sun, M.D.    86 010 66583761    xinsun1981@hotmail.com   
Peking University Shougang Hospital Recruiting
Beijing, China, 100144
Contact: Lu Xie, M.D.    86 010 57830370    sweetdoctor@163.com   
Peking University Third Hospital Not yet recruiting
Beijing, China, 100191
Contact: Liang Jiang, M.D       jiangliang@bjmu.edu.cn   
People's Liberation Army General Hospital Not yet recruiting
Beijing, China, 100853
Contact: Wenzhi Bi, M.D       biwenzhi@sina.com   
Sponsors and Collaborators
Peking University People's Hospital
Investigators
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Principal Investigator: Wei Guo, M.D, Ph.D Peking University People's Hospital
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Responsible Party: GUO WEI, Director of Musculoskeletal Tumor Center, Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT03416517    
Other Study ID Numbers: PKUPH-EWS-02
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GUO WEI, Peking University People's Hospital:
Ewing Sarcoma
Anlotinib
Irinotecan
Refractory
Metastatic
Additional relevant MeSH terms:
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Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents