NCT03390946

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
23

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2018

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 11, 2017

Completed
25 days until next milestone

First Posted

Study publicly available on registry

January 5, 2018

Completed
27 days until next milestone

Study Start

First participant enrolled

February 1, 2018

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2020

Completed
Last Updated

January 9, 2018

Status Verified

January 1, 2018

Enrollment Period

2.9 years

First QC Date

December 11, 2017

Last Update Submit

January 5, 2018

Conditions

OsteosarcomaFeasibilityTreatment ResponseBiomarker

Keywords

four-drugs, interval-compression

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • tumor necrosis rate

    Until study completion, an average of 3years

  • Predictive or prognostic biomarker

    Until study completion, an average of 3 years

Study Arms (1)

four-drug interval-compressed regimen

EXPERIMENTAL

Interventions for 'four-drug interval-compressed regimen': Drug: methotrexate, cisplatin, doxorubicin, ifosfamide. Newly diagnosed oseteosarcoma patients under 40 years are eligible. Neoadjuvant chemotherapy with four drugs in an interval-compressed schedule will be done as a single arm. Duration of neoadjuvant chemotherapy will be 10 weeks like that of conventional three-drug regimen, although four-drugs are employed in the current protocol. After tumor resection operation, participants will be divided to poor responder group and good responder group based on 90% necrosis rate of a tumor specimen. Poor responder group and will be assigned to 'Poor responder group adjuvant chemotherapy' and good responder will be assigned to 'Good responder group adjuvant chemotherapy'.

Drug: Poor responder group adjuvant chemotherapyDrug: Good responder group adjuvant chemotherapy

Interventions

Poor responder group adjuvant chemotherapyDRUG

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 1. 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 2. 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

Also known as: PR adjuvant four-drug interval-compressed regimen
four-drug interval-compressed regimen
Good responder group adjuvant chemotherapyDRUG

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

Also known as: GR adjuvant four-drug interval-compressed regimen
four-drug interval-compressed regimen

Eligibility Criteria

AgeUp to 40 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Newly diagnosed osteosarcoma patients under age 40 years.

You may not qualify if:

  • Patients who don't meet the organ function criteria as follows;
  • renal function : CCr or GFR or eGFR ≥ 70 mL/min/1.73 m2
  • liver function : AST/ALT ≤ 5 x upper limit, total bilirubin ≤ 1.5 x upper limit of normal for age
  • cardiac function : shortening fraction ≥ 24% or ejection fraction ≥ 50% (Echo)
  • lung function : No dyspnea on rest, If dyspnea exists, SpO2 95% or more in room air by pulse oximetry,
  • hematologic : ANC ≥ 750/uL and platelet ≥ 75,000/uL

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Related 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. doi: 10.1093/jnci/djk015.

    PMID: 17227995BACKGROUND

  • 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: 27569442BACKGROUND

MeSH Terms

Conditions

Osteosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsSarcoma

Study Officials

  • Byung-Kiu Park, M.D., Ph.D.

    National Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Byung-Kiu Park, M.D., Ph.D.

CONTACT

82-31-920-1240bkpark@ncc.re.kr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

December 11, 2017

First Posted

January 5, 2018

Study Start

February 1, 2018

Primary Completion

December 31, 2020

Study Completion

December 31, 2020

Last Updated

January 9, 2018

Record last verified: 2018-01

Locations

KR(1)