Clinical trial NCT03416517: Anlotinib and Irinotecan for Ewing Sarcoma
Official title: Anlotinib and Irinotecan for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Ewing's Tumor Metastatic
Keywords: Ewing Sarcoma
Anlotinib
Irinotecan
Refractory
Metastatic
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2018-01-31
Enrollment: 47
Sex: ALL
Minimum age (years): 5
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) (phase 1b)
timeFrame: 12 months
measure: Object response rate(ORR) at 12 weeks (phase 2)
timeFrame: 12 months
Secondary outcomes:
measure: Progression-free survival(PFS)
timeFrame: 2 years
measure: Overall survival(OS)
timeFrame: 2 years
measure: Adverse Effect
timeFrame: 2 years
measure: Quality of Life (QoL)
timeFrame: 2 years
measure: Pain management
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Peking University Shougang Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Beijing
country: China
facility: People's Liberation Army General Hospital
Study officials:
affiliation: Peking University People's Hospital
name: Wei Guo, M.D, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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.