Feasibility Study of Interval Compressed Regimen Using Four-drugs for Osteosarcoma

Osteosarcoma Clinical Trial

Official title:

Feasibility Study of Interval Compressed Regimen Using Four-drugs for Osteosarcoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03390946
• Other study ID #: NCC-OSA-1601
• Status: Not yet recruiting
• Phase: Phase 2
• First received: December 11, 2017
• Last updated: January 5, 2018
• Start date: February 1, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: January 2018
• Source: National Cancer Center, Korea
• Contact: Byung-Kiu Park, M.D., Ph.D.
• Phone: 82-31-920-1240
• Email: bkpark[@]ncc.re.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to test the feasibility of four-drug, interval-compressed regimen in osteosarcoma.

Primary objective is to explore the toxicity and mortality related to treatment. Secondary objectives are to examine tumor necrosis rates after neoadjuvant chemotherapy, and to evaluate the usefulness of circulating cell-free DNA, survivin, or transforming growth factor-beta1 levels as well as programmed cell death ligand 1 expression in tumor specimen as a predictive or prognostic biomarker in osteosarcoma patients.

Description:

In this study, the investigators will investigate the feasibility of interval compressed regimen using four-drugs in newly-diagnosed osteosarcoma patients. Four drugs will be adriamycin, high-dose methotrexate, cisplatin, ifosfamide. All these drugs will be given preoperatively in an interval-compressed schedule, but postoperatively at a regular interval. Neoadjuvant therapy will be composed of two courses, and adjuvant therapy of two or three courses depending on necrosis rates following neoadjuvant therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 23
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 40 Years

Eligibility

Inclusion Criteria:

• Newly diagnosed osteosarcoma patients under age 40 years.

Exclusion Criteria:

• Patients who don't meet the organ function criteria as follows;

1. renal function : CCr or GFR or eGFR = 70 mL/min/1.73 m2

2. liver function : AST/ALT = 5 x upper limit, total bilirubin = 1.5 x upper limit of normal for age

3. cardiac function : shortening fraction = 24% or ejection fraction = 50% (Echo)

4. lung function : No dyspnea on rest, If dyspnea exists, SpO2 95% or more in room air by pulse oximetry,

5. hematologic : ANC = 750/uL and platelet = 75,000/uL

Related Conditions & MeSH terms

• Biomarker
• Feasibility
• Osteosarcoma
• Treatment Response

Intervention

Drug:
• Poor responder group adjuvant chemotherapy
Poor responder group (necrosis = 90%) : week 0, 7 and 14, doxorubicin; week 2, 9 and 16, ifosfamde, week 4, 11, 18 and 19, methotrexate; wk 5, 12 and 20 B. Resection of tumor C. Adjuvant chemotherapy Poor responder group (necrosis = 90%) week 0, 7 and 14, doxorubicin; week 2, 9 and 16, ifosfamde, week 4, 11, 18 and 19, methotrexate; wk 5, 12 and 20 Good responder group (necrosis > 90%) week 0 and 8, doxorubicin; week 2 and 10, ifosfamide; week 4, 5, 12 and 13, methotrexate; week 6 and 14, cisplatin
• Good responder group adjuvant chemotherapy
Good responder group (necrosis > 90%) : week 0 and 8, doxorubicin; week 2 and 10, ifosfamide; week 4, 5, 12 and 13, methotrexate; week 6 and 14, cisplatin

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi

Sponsors (3)

Lead Sponsor	Collaborator
Byung-Kiu Park	Chungnam National University Hospital, Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, Memon MA, Weeden S, Uscinska BM, van Glabbeke M, Kirkpatrick A, Hauben EI, Craft AW, Taminiau AH; MRC BO06 and EORTC 80931 collaborators; European Osteosarcoma Intergroup. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007 Jan 17;99(2):112-28. — View Citation

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, Jürgens H, Kager L, Kühne 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity determined according to CTCAE	treatment-related toxicity (organ dysfunction, neutropenic fever, infection, mortality, et al.)	Until study completion, an average of 3 years
Secondary	tumor necrosis rate	necrosis rate of the excised tumor after neoadjuvant chemotherapy	Until study completion, an average of 3years
Secondary	Predictive or prognostic biomarker	Usefulness of circulating cell-free DNA, survivin, transforming growth factor-beta1 levels and programmed cell death 1 expression in tumor specimen as a biomarker	Until study completion, an average of 3 years