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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/23/2021.

Epigenetic Biomarker for Advanced Osteosarcoma Using Famitinib and Camrelizumab

Clinicaltrials.gov identifier NCT03919539

Recruitment Status Recruiting

First Posted April 18, 2019

Last update posted February 6, 2020

Study Description

Brief summary:

hMe-Seal is a low-input whole-genome cell-free 5hmC sequencing method based on selective chemical labeling. It uses β-glucosyltransferase (βGT) to selectively label 5hmC with a biotin via an azide-modified glucose for pull-down of 5hmC-containing DNA fragments for sequencing. After selectively constructing 5hmC library, highthroughput-sequencing will be performed on an Illumina Nextseq-500 instrument. By ways of Rawdata processing, differential loci between Osteosarcoma group and control group will be detected to indentify specific epigenetic biomarkers of Osteosarcoma. From our previous trials, we identify geno sequencing related to beta-catenin pathways might have some relationship with osteosaroma primary or secondary drug resistance. Thus in this trial we try to further explore the drug resistance mechanism for advaced osteosarcoma second resistance to the combination therapy of Famitinib and Camrelizumab.

  • Condition or Disease:Drug Resistance to Famitinib and Camrelizumab
    Biomarkers for Efficacy and Toxicity
  • Intervention/Treatment: Diagnostic Test: 5hmc testing
  • Phase: N/A
Detailed Description

N/A

Study Design
  • Study Type: Observational [Patient Registry]
  • Estimated Enrollment: 40 participants
  • Observational Model: Case-Only
  • Time Perspective: Prospective
  • Official Title: Indentifying Epigenetic Biomarkers From Peripheral Blood of Advanced Osteosarcoma Patients, Who Recieve Famitinib and Camrelizumab Based on hMe-Seal Technique
  • Actual Study Start Date: December 2019
  • Estimated Primary Completion Date: June 2021
  • Estimated Study Completion Date: December 2021
Outcome Measures
  • Primary Outcome Measures: 1. 5hmc expression rate [ Time Frame: 24 months ]
  • Biospecimen Retention: Samples With DNA

    cfDNA samples were prepared from peripheral blood collected from patients. Briefly, 8 ml of peripheral blood was collected from each subject using EDTA anticoagulant tubes, and the plasma sample was prepared within 6 h by centrifuging twice at 1 350× g for 12 min, and then centrifuging at 13500× g for 12 min. The prepared plasma samples (about 2 ml/subject) were immediately stored at -80 °C. The plasma cfDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (Qiagen) according to the manufacturer's protocol.

Eligibility Criteria
  • Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
  • Sampling Method: Non-Probability Sample
  • Study Population: Results of previous study showed high objective response but short-term activity of famitinib in advanced osteosarcoma. Given the recent success of immunotherapies, combinations of antiangiogenics with immune checkpoint blockers have become an attractive strategy. We aimed to investigate the activity of famitinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.
Criteria

Subjects can be enrolled in this study only when they meet all the inclusion criteria:

- Provided informed consent and sign the informed consent form;

- ≥12 years old for male and ≥ 11 years old for female;

- Histopathologically or cytologically confirmed Advanced Osteosarcoma; (Local tumors
and solitary pulmonary lesions must be confirmed by pathological diagnosis. Multiple
pulmonary metastases need no pathological examination.)

- Failed to receive chemotherapy for osteosarcoma (including HD-MTX, anthracyclines, DDP
and IFO) are defined as those who progress within 6 months after adjuvant chemotherapy
and chemotherapy for advanced osteosarcoma, and those who progress over 6 months
require the consent of the subject or his legal representative.;

- Have at least one measurable lesion (in accordance with RECIST v1.1, major diameter
≥10 mm of the measurable lesion in spiral CT scan or short diameter of swollen lymph
node ≥15 mm; the lesion with previous local therapy can be used as target lesion after
the progression is confirmed in accordance with RECIST v1.1);

- For subjects with progression after local regional therapy, the local regional therapy
(including but not limited to surgery, radiotherapy, hepatic artery embolization,
TACE, hepatic arterial infusion, radiofrequency ablation, cryoablation or percutaneous
ethanol injection) must has been completed at least 4 weeks prior to baseline
radiological scanning, and any toxicity (except alopecia) induced by local regional
therapy must have resolved to ≤ Grade 1 in accordance with national cancer institute -
common terminology criteria for adverse event version 4.03 (NCI-CTCAE v4.03);

- ECOG-PS score 0-1;

- With a life expectancy of ≥12 weeks;

- Have the required screening laboratory values including the following parameters
(within 7 days prior to the start of study treatment):

(1) Hematology: (except for hemoglobin, no blood transfusion or use of granulocyte
colony-stimulating factor [G-CSF] or use of drugs for correction within 14 days prior
to screening); Absolute neutrophil count ≥0.75×109/L; Platelet count ≥75×109/L;
Hemoglobin ≥80 g/L; (2) Blood biochemistry: (no infusion of albumin within 14 days):
Serum albumin ≥25 g/L; Serum total bilirubin ≤1×upper limit of normal (ULN); Alanine
aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase
(AKP) ≤2.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or Cr clearance >50 mL/min
(Cockcroft-Gault formula as below) Man: Cr clearance =((140-age) ×weight)/(72×serum
Cr) Woman: Cr clearance =((140-age) ×weight)/ (72×serum Cr) × 0.85 Weight unit: kg;
serum Cr unit: mg/mL;

- Women of childbearing potential: must agree on abstinence (avoid heterosexual
intercourse) or use of contraception methods with annual contraceptive failure rate of
325 mg/day) or dipyridamole, ticlopidine, clopidogrel and cilostazol;

- Thrombosis or thromboembolic event within 6 months prior to the start of study
treatment, for example, cerebrovascular accident (including transient ischemic attack,
cerebral hemorrhage, cerebral infarction), pulmonary embolism;

- Cardiac clinical symptom or disease that is not well controlled, for example, (1) >
Grade II cardiac insufficiency in accordance with New York Heart Association (NYHA)
criteria or color Doppler echocardiography: LVEF (left ventricular ejection fraction)
450 ms (males)
or QTc > 470ms (females) (QTc interval is calculated by Fridericia formula; In case
QTc is abnormal, it can be detected for three times at an interval of 2 minutes and
the average will be taken);

- Hypertension that can not be well controlled through antihypertensive drugs (systolic
blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) (based on the average
of BP readings acquired from ≥2 measurements), allowing to reach the above parameters
by the use of antihypertensive therapy; previous hypertensive crisis or hypertensive
encephalopathy;

- Major vascular disease within 6 months prior to the start of study treatment (for
example, aortic aneurysm requiring surgical repair or peripheral arterial thrombosis
in recent days);

- Serious, uncured or splitting wound and active ulcer or untreated bone fracture;

- Major surgical therapy within 4 weeks prior to the start of study treatment (except
diagnosis), or expected major surgery during the study;

- Inability or unwilling to swallow tablets, malabsorption syndrome or any condition
affecting gastrointestinal absorption;

- Intestinal obstruction and/or clinical signs or symptoms of gastrointestinal
obstruction within 6 months prior to the start of study treatment, including
incomplete obstruction that is related with the original disease or needs routine
parenteral hydration, parenteral nutrition or tube feeding; If the subject has
signs/symptoms of incomplete obstruction/ obstructive syndrome/intestinal obstruction
at the initial diagnosis receives clear (surgical) therapy to resolve symptoms, the
subject may be enrolled;

- Evidence on intraperitoneal pneumatosis that can not be explained by puncture or
recent surgery;

- Previous or current presence of metastasis to central nervous system;

- Previous or present history of pulmonary fibrosis, organising pneumonia (e.g.,
obliterative bronchiolitis), interstitial pneumonia, pneumoconiosis, drug related
pneumonitis, idiopathic pneumonia, or allowable previous radiation pneumonitis in the
radiation area (fibrosis) for subjects with evidence on active pneumonia or serious
pulmonary function impairment on thoracic computed tomography (CT) in screening period
that may interfere with the detection and treatment of suspected drug related
pulmonary toxicity; active tuberculosis;

- Any active autoimmune disease or history of autoimmune disease and expected recurrence
(including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis,
enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism
[subjects that can be controlled with hormone replacement therapy only can be
enrolled]); subjects with skin diseases that does no need systemic treatment, for
example, leukoderma, psoriasis, alopecia, those with controlled type I diabetes by
insulin or those with asthma that has been completely resolved in childhood and with
no need of any intervention can be enrolled; while subjects with asthma who need
bronchodilator for medical intervention can not be enrolled;

- Current use of immunosuppressive medication, or systemic corticosteroid therapy to
achieve the objective of immunosuppression (Prednisone at the dose of >10mg/day or
equivalent), and continuous use within two weeks prior signing informed consent form;

- Use of strong CYP3A4/CYP2C19 inducers, including rifampicin (and its analogues) and
St. Jonhn's Wort, or strong CYP3A4/CYP2C19 inhibitors within two weeks prior to the
signature of informed consent form;

- Known history of serious allergy to any monoclonal antibody or targeted
anti-angiogenic drug;

- Severe infection within 4 weeks prior to the start of study treatment, including but
not limited to hospitalization for infection, bacteremia or complications of severe
pneumonia; oral or intravenous therapeutic antibiotics within two weeks prior to the
start of study treatment (for example, subjects who are given with preventive
antibiotics for prevention of urinary tract infection or exacerbation of chronic
obstructive pulmonary disease are eligible for participation in the study);

- Congenital or acquired immunodeficiency (e.g., HIV infection);

- Combined hepatitis B and hepatitis C co-infection;

- Previous treatment with other PD-1 antibody or other immunotherapy against PD-1/PD-L1,
or previous use of other small molecules of anti-angiogenesis TKI drugs, such as
pazopanib, sorafenib;

- Palliative radiotherapy for non-target lesions to control symptoms is allowed, but it
must be completed at least 2 weeks prior to the start of study treatment, and the
adverse event induced by radiotherapy must have resolved/improved to ≤CTCAE Grade 1;

- Treatment of other investigational product(s) within 28 days prior to the start of
study treatment;

- Other factors that may affect the study results or lead to forced termination of the
study early as judged by investigators, such as alcoholism, drug abuse, other serious
diseases (including mental disorders) requiring concomitant therapy, with serious
laboratory examination abnormality, with family or social factors, that may affect
subject's safety.

Contacts and Locations
Contacts

Contact: Lu Xie, M.D. +8613401044719 xie.lu@hotmail.com

Contact: Jie Xu, M.D. +8615901040835 xujie_pkuph@sina.com

Locations

China, Beijing
Peking University People's Hospital
Beijing

Sponsors and Collaborators

Peking University People's Hospital

Peking University

Northwestern University

Investigators

Principal Investigator: Wei Guo, M.D. and Ph.D. Musculoskeletal Tumor Center of Peking University People's Hospital

More Information
  • Responsible Party: Peking University People's Hospital
  • ClinicalTrials.gov Identifier: NCT03919539 History of Changes
  • Other Study ID Numbers: PKUPH- sarcoma 06
  • First Posted: April 18, 2019 Key Record Dates
  • Last Update Posted: February 6, 2020
  • Last Verified: February 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Peking University People's Hospital: osteosarcoma
    5hmc
    drug resistance
    famitinib
    camrelizumab
  • Additional relevant MeSH terms: Osteosarcoma