Epigenetic Biomarker for Osteosarcoma

NCT03336554 | Unknown DMC

• 1 other identifier: CBTRA-02
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Histologic Response (Tumor Necrosis Rate); Objective Response Rate for Neoadjuvant Chemotherapy, ORR; Progression-free Survival, PFS; Overall Survival, OS

Keywords

osteosarcoma; epigenetic biomarker; hMe-Seal technique

Outcome Measures

Primary Outcomes (1)

• Histologic response

  For osteosarcoma, tumor necrosis rate will be done for every participant. On pathologic examination, the surgical specimens were carefully studied and sectioned. This evaluation included establishing the gross extent of the tumor\[26, 27\] and noting its soft tissue component and lines of surgical resection\[27\]. An average of 10-20 histologic specimens were examined in each of the en bloc resections to delineate the extension of osteosarcoma up and down the marrow cavity and to study the effects of chemotherapy on the tumor (viable, partially, largely, or totally necrotic), which were then calculated as tumor necrosis rate as paper described.

  2 months

Secondary Outcomes (3)

• Objective Response Rate

  2 months

• Progression-free survival

  2 years

• Overall survival

  5 years

Study Arms (1)

observation group

One group of participants are under observation. This trial has two phase. Phase I: 40 participants will be enrolled. Only if epigenetic cfDNA library has been built, investigators would move on to Phase II. Another 60 participants will be enrolled for further analysis.

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Biopsy proved high-grade osteosarcoma, who should be older than 10 years and could complete routine chemo-protocol for osteosarcoma, could get enrolled.

You may qualify if:

• \) histologically confirmed high-grade osteosarcoma;
• \) older than 10 yrs;
• \) initially treated in Musculoskeletal Tumor Center of Peking University People's Hospital;
• \) Serum samples are available;
• \) completed neo-adjuvant chemotherapy and at least 8 cycles of adjuvant chemotherapy;
• \) expected to live longer than 3 months with Eastern Cooperative Oncology Group performance status of 0 or 1;
• \) acceptable hematologic, hepatic, and renal function.

You may not qualify if:

• \) Serum samples are not qualified;
• \) Patients who could not complete neo-adjuvant chemotherapy or at least 4-month adjuvant chemotherapy;
• \) lost to follow-up.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Peking University: collaborator
• Northwestern University: collaborator
• University of Chicago: collaborator

Study Sites (1)

Peking University People's Hospital

Beijing, 100044, China

RECRUITING

Related Publications (12)

• Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC, Tap WD. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 2012 Dec 1;118(23):5888-93. doi: 10.1002/cncr.27651. Epub 2012 May 30.

  PMID: 22648705 BACKGROUND

• Bielack S, Jurgens H, Jundt G, Kevric M, Kuhne T, Reichardt P, Zoubek A, Werner M, Winkelmann W, Kotz R. Osteosarcoma: the COSS experience. Cancer Treat Res. 2009;152:289-308. doi: 10.1007/978-1-4419-0284-9_15.

  PMID: 20213397 BACKGROUND

• Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KLB, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PCW, Isakoff MS, Janeway KA, Jurgens H, Kager L, Kuhne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MCG, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. doi: 10.1016/S1470-2045(16)30214-5. Epub 2016 Aug 25.

  PMID: 27569442 BACKGROUND

• Duchman KR, Gao Y, Miller BJ. Prognostic factors for survival in patients with high-grade osteosarcoma using the Surveillance, Epidemiology, and End Results (SEER) Program database. Cancer Epidemiol. 2015 Aug;39(4):593-9. doi: 10.1016/j.canep.2015.05.001. Epub 2015 May 20.

  PMID: 26002013 BACKGROUND

• Tang XD, Guo W, Yang RL, Yang Y, Ji T. [Limb salvage surgery for osteosarcoma around the knee in children and adolescent patients]. Zhonghua Wai Ke Za Zhi. 2007 May 15;45(10):669-72. Chinese.

  PMID: 17688817 BACKGROUND

• Xie L, Guo W, Tang X, Yang Y, Xu J. Effects of Arsenic Trioxide on Minor Progressive High-Grade Osteosarcoma of the Extremities Metastatic to the Lung: Results of 39 Patients Treated in a Single Institution. Case Rep Oncol. 2016 Oct 17;9(3):610-628. doi: 10.1159/000448705. eCollection 2016 Sep-Dec.

  PMID: 27920692 BACKGROUND

• Guo W, Sun X, Ji T, Tang X. Outcome of surgical treatment of pelvic osteosarcoma. J Surg Oncol. 2012 Sep 15;106(4):406-10. doi: 10.1002/jso.23076. Epub 2012 Feb 27.

  PMID: 22371155 BACKGROUND

• Fei D, Li Y, Zhao D, Zhao K, Dai L, Gao Z. Serum miR-9 as a prognostic biomarker in patients with osteosarcoma. J Int Med Res. 2014 Aug;42(4):932-7. doi: 10.1177/0300060514534643. Epub 2014 Jun 24.

  PMID: 24962996 BACKGROUND

• Fu HL, Shao L, Wang Q, Jia T, Li M, Yang DP. A systematic review of p53 as a biomarker of survival in patients with osteosarcoma. Tumour Biol. 2013 Dec;34(6):3817-21. doi: 10.1007/s13277-013-0966-x. Epub 2013 Sep 7.

  PMID: 24014053 BACKGROUND

• Bachman M, Uribe-Lewis S, Yang X, Williams M, Murrell A, Balasubramanian S. 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem. 2014 Dec;6(12):1049-55. doi: 10.1038/nchem.2064. Epub 2014 Sep 21.

  PMID: 25411882 BACKGROUND

• Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 2004 Aug 9;32(14):4100-8. doi: 10.1093/nar/gkh739. Print 2004.

  PMID: 15302911 BACKGROUND

• Chapman CG, Mariani CJ, Wu F, Meckel K, Butun F, Chuang A, Madzo J, Bissonnette MB, Kwon JH, Godley LA. TET-catalyzed 5-hydroxymethylcytosine regulates gene expression in differentiating colonocytes and colon cancer. Sci Rep. 2015 Dec 3;5:17568. doi: 10.1038/srep17568.

  PMID: 26631571 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood with enough free DNA should be segregation. If the peripheral blood is not taken properly, it should be disposed of it or blood should be drawn again for DNA amplication and analysis.

MeSH Terms

Conditions

Osteosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Wei Guo, M.D.and Ph.D.

  Musculoskeletal Tumor Center of Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lu Xie, M.D.

CONTACT

+86-13401044719; sweetdoctor@163.com

Jie Xu, M.D

CONTACT

+86-15901040835; xujie_pkuph@sina.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 8, 2017
• Study Start: September 1, 2017
• Primary Completion: October 30, 2018
• Study Completion: December 31, 2018
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

CN (1)