Study to identify an appropriate Modufolin® dose with respect to safety and ability to mitigate high-dose Methotrexate induced toxicity in osteosarcoma patients.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 18

Inclusion Criteria

1.Patients must have histological evidence of osteosarcoma including metastatic osteosarcoma.
2.Patients must be eligible for high-dose methotrexate treatment (HDMTX) according to the MAP treatment schedule described in the study protocol (see Appendix 1) and fulfill all of the criteria below prior to first course of HDMTX in the study.
a.Serum MTX: = 0.1µmol/L
b.Neutrophils: = 0.25 x 109/L
c.Platelets: = 50 x 109/L
d.Serum bilirubin: = 1.25 x ULN
e.GFR = 70 mL/min/1.73 m2
f.No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator.
3.Patients must be enrolled in HDMTX course 1, 3 or 5 of the MAP treatment schedule (see Appendix 1).
4.Patients enrolled in HDMTX course 3 or 5 must have a history of successful advancement from first to second HDMTX course within the previous MAP cycle, i.e. fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:
a.Serum MTX: = 0.1µmol/L
b.Neutrophils: = 0.25 x 109/L
c.Platelets: = 50 x 109/L
d.Serum bilirubin: = 1.25 x ULN
e.GFR = 70 mL/min/1.73 m2
f.No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator.
5.Patients enrolled in HDMTX course 3 or 5 must have a history of successful advancement to next MAP cycle after end of previous MAP cycle, i.e. fulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:
a.Serum MTX: = 0.1µmol/L
b.Neutrophils: = 0.75 x 109/L
c.Platelets: = 75 x 109/L
d.Serum bilirubin: = 1.25 x ULN
e.GFR = 70 mL/min/1.73 m2
f.No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator.
6.Patients must be 12-40 years of age. The age limit may be lowered to 6-40 years for enrolment in Cohort 2 (only) and if recommended by the
DSMB.
7.Sexually active females of childbearing potential: Must be surgically sterile, or compliant with a contraceptive regimen during and for six (6) months after last MTX dose in MAP regimen; must have a negative serum or urine pregnancy test (within seven (7) days before study enrolment) and must not be lactating.
8.Sexually active males: Must be surgically sterile or compliant with a contraceptive regimen during and for six (6) months after last MTX dose in MAP regimen.
9.Patient, parent(s), or guardian(s), as appropriate, is/are willing and able to provide signed informed consent.
10.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol.
11.Patients who have undergone surgical resection of their tumor must have recovered from their surgery and be eligible to continue on the MAP regimen; any post-operative complications should be resolved to NCI CTCAE v4.0 Grade 1 or better.

Are the trial subjects under 18? yes
Number of subjects for this age range: 18
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Involvement in another clinical trial within 30 days before enrolment in the study.
2.Hypersensitivity to Calcium Folinate.
3.Previous treatment with glucarpidase.
4.Known serious concomitant systemic disorders (e.g., active infection including HIV, liver dysfunction, cardiac disease) that, in the opinion of the investigator, would compromise the patient's ability to complete the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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