OsteosarcomaPhase 1/2NCT01987102
Investigation of [6R] 5,10-methylenetetrahydrofolate (Arfolitixorin) as Rescue Therapy for Osteosarcoma Patients Treated With HDMTX.
A Phase 1/2 study testing Calcium Folinate and [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) in people with Osteosarcoma, run by Isofol Medical AB at 5 sites in 4 countries.
Trial summary
An open-label, multicenter, phase I/II clinical trial to identify the [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) dose with most favorable safety prospect and confirmed ability to mitigate high-dose methotrexate induced toxicity during treatment of osteosarcoma patients Read more about this study
- Who is it for?
- Ages 6 to 40 years
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- Calcium Folinate and [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Dec 2013to 3 Jan 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Involvement in another clinical trial within 30 days before enrolment in the study.
- Hypersensitivity to Calcium Folinate.
- Previous treatment with glucarpidase.
- 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
- Main Inclusion criteria for continuation (HDMTX treatment with Modufolin rescue):
- Patients, who were included in the study in accordance with the inclusion criteria above, must have received 2 adjacent courses of HDMTX with SOC rescue according to the MAP treatment schedule in accordance with this study protocol.
Show all 10Show fewer
- Patients eligible for continued HDMTX according to the MAP treatment schedule and with a history of successful advancement from first to second HDMTX course within the previous MAP cycle
- Patients eligible for continued HDMTX according to the MAP treatment schedule and with a history of successful advancement to next MAP cycle after end of previous MAP cycle
- No significant changes to the patient's medical condition from the start of the study that in the opinion of the investigator would compromise the patient's ability to complete the study.
- 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.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Czechia2 sites
Fakultní nemocnice Brno Klinika detske onkologie
Brno, 62500
Fakultní nemocnice v Motole
Prague, 15006
Hungary1 site
Semmelweis Egyetem II. Sz. Gyermekgyógyászati Klinika
Budapest, 1094
About this study
Official title: An Open-Label, Multicenter, Phase I/II Clinical Trial to Identify the Modufolin® Dose With Most Favorable Safety Prospect and Confirmed Ability to Mitigate High-Dose Methotrexate Induced Toxicity During Treatment of Osteosarcoma Patients
An open-label, multicenter, phase I/II clinical trial to identify the [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) dose with most favorable safety prospect and confirmed ability to mitigate high-dose methotrexate induced toxicity during treatment of osteosarcoma patients
Read the detailed description
This is a non-blinded, multicenter, exploratory study in osteosarcoma patients. The study focuses on the overall safety of the HDMTX courses given within a Methotrexate, Adriamycin (doxorubin) and cisPlatin (MAP) treatment schedule, which is closely related to the efficacy of the concomitantly administered folate rescue treatment. Additionally the study aimes to collect pharmacokinetic (PK) profiles of metotrexate (MTX) in serum, of folate metabolites in plasma and to decide the Modufolin® dose to use in future studies.
Patients are enrolled in the study at the first, third or the fifth HDMTX course in a MAP treatment schedule and receive folate rescue therapy according to a strategy based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331.
Folate rescue treatment with Calcium Folinate (SOC) or Modufolin® (MOD) commence 24 h after start of HDMTX administration and then every 6 h until the serum MTX levels are ≤0.1 μmol/L. In case delayed MTX elimination occurs with significant increase in S-creatinine and/or occurrence of oral mucositis or signs of hypo cellular bone marrow, the folate rescue dose and/or the administered hydration will be adjusted in accordance with the COG based MTX toxicity management recommendations.
All patients receives SOC (15 mg/m2) in the first 2 HDMTX courses and MOD in the following 2 courses. Patients are enrolled in one of two MOD dose cohorts: Cohort 1 (15 mg/m2) and Cohort 2 (30 or 7.5 mg/m2 depending on outcome of Cohort 1). Only patients with successful advancements from the first 2 HDMTX courses with Calcium Folinate are allowed to continue with MOD as rescue in the following MAP cycle.
Safety data will be reviewed by an independent board, Data and Safety Monitoring Board (DSMB) that will assess each patient and made recommendations regarding the enrolment of subsequent patients. Furthermore, the DSMB will make a dose level recommendation for Cohort 2 and also a recommendation whether younger children may be allowed in this cohort.
- Conditions
- Osteosarcoma
- Being tested
- Calcium Folinate, [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)
- Keywords
- Methotrexate, Rescue treatment
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Calcium FolinateDrug
Also called Leucovorin
The enrolled patients will be treated according to the MAP schedule and will receive the study drug Calcium Folinate commencing 24 hours after the administration of HDMTX and then every 6 hours (q6h) thereafter until the S-MTX levels are ≤ 0.1 µmol/L, in accordance with COG management recommendations.
All patients will receive standard o care (SOC) in the two (2) first HDMTX courses and [6R] 5,10-methylenetetrahydrofolate in the two (2) following courses. Patients will be enrolled in two (2) [6R] 5,10-methylenetetrahydrofolate dose cohort groups: with [6R] 5,10-methylenetetrahydrofolate start dose of 15 mg/m2 (i.e. the same as for SOC rescue) the first cohort will be administered, and 7.5 or 30 mg/m2 in the second cohort.
[6R] 5,10-methylenetetrahydrofolate (arfolitixorin)Drug
Also called Modufolin, arfolitixorin
The enrolled patients will be treated according to the MAP schedule and will receive the study drug [6R] 5,10-methylenetetrahydrofolate commencing 24 hours after the administration of HDMTX and then every 6 hours (q6h) thereafter until the S-MTX levels are ≤ 0.1 µmol/L, in accordance with COG management recommendations.
All patients will receive standard o care (SOC) in the two (2) first HDMTX courses and [6R] 5,10-methylenetetrahydrofolate in the two (2) following courses. Patients will be enrolled in two (2) [6R] 5,10-methylenetetrahydrofolate® dose cohort groups: with [6R] 5,10-methylenetetrahydrofolate start dose of 15 mg/m2 (i.e. the same as for SOC rescue) the first cohort will be administered, and 7.5 or 30 mg/m2 in the second cohort.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 1 MAP cycle (incl. 2 HDMTX Courses using Calcium Folinate rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX Courses using [6R] 5,10-methylenetetrahydrofolate rescue 15mg/m2) Receives: Drug: Calcium Folinate; Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) |
| Cohort 2 | Experimental | 1 MAP cycle (incl. 2 HDMTX Courses using Calcium Folinate rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX Courses using [6R] 5,10-methylenetetrahydrofolate rescue 7,5mg/m2 or 30mg/m2*)
*Dose will depend on outcome from Cohort 1 Receives: Drug: Calcium Folinate; Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of AEs Per Severity (All Courses)
Characterization (number and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Measured: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total
Number of HDMTX Related AEs Per Severity (All Courses)
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Measured: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total
Number of Ongoing AEs Per HDMTX Course
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Measured: From the start of HDMTX administration through 8 days post dose for each course of HDMTX
Number of Ongoing HDMTX Related AEs Per HDMTX Course
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Measured: From the start of HDMTX administration through 8 days post dose for each course of HDMTX
Secondary outcomes (10)
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Definition A: Successful advancement from 1st to 2nd HDMTX course within the same MAP cycle. Fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:
- Serum MTX: ≤0.1μmol/L
- Neutrophils: ≥0.25x109/L
- Platelets: ≥50x109/L
- Serum bilirubin: ≤1.25 x upper limit of normal (ULN)
- Glomerular filtration rate (GFR) ≥70 mL/min/1.73m2
- No AE Grade 2 or more related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator
Definition B: Successful advancement to next MAP cycle
Fulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:
- Serum MTX: ≤0.1μmol/L
- Neutrophils: ≥ 0.75 x 109/L
- Platelets: ≥75x109/L
- Serum bilirubin: ≤1.25xULN
- GFR ≥70 mL/min/1.73m2
- No AE Grade 2 or more related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator
Measured: 8 days after start of first and/or second HDMTX course in a MAP cycle
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.
Definition A: Successful advancement from first to second HDMTX course within the same MAP cycle
Fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:
- Serum MTX: ≤ 0.1 μmol/L
- Neutrophils: ≥ 0.25 x 109/L
- Platelets: ≥ 50 x 109/L
- Serum bilirubin: ≤ 1.25 x ULN
- GFR ≥ 70 mL/min/1.73 m2
- No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator
Measured: 8 days after start of first HDMTX course in a MAP cycle
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.
Definition B: Successful advancement to next MAP cycle
Fulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:
- Serum MTX: ≤ 0.1 μmol/L
- Neutrophils: ≥ 0.75 x 109/L
- Platelets: ≥ 75 x 109/L
- Serum bilirubin: ≤ 1.25 x ULN
- GFR ≥ 70 mL/min/1.73 m2
- No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator
Measured: 8 days after start of second HDMTX course in a MAP cycle
Time to Successful MTX Elimination (Definition C)
Definition C: Time to successful MTX elimination = Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Measured: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Measured: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Definition D: Delayed MTX elimination (according to COGs excretion toxicity management instructions)
S-MTX levels of:
> 10 μmol/L at 24 h after start of MTX administration, OR > 1 μmol/L at 48 h after start of MTX administration, OR > 0.1 μmol/L at 72 h after start of MTX administration or later
Measured: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Definition E: Delayed early MTX elimination (according to US label for Calcium Folinate)
S-MTX levels of:
- 50 μmol/L at 24 hours after start of MTX administration, OR
- 5 μmol/L at 48 hours after start of MTX administration OR An increase in S-Creatinine level of 100% or greater at 24 hours after start of MTX administration.
Measured: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Definition F: Delayed late MTX elimination (according to US label for Calcium Folinate)
S-MTX level:
> 0.2 μmol/L at 72 hours AND > 0.1 μmol/L at 96 hours after start of MTX administration.
Measured: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
The MTX-toxicity management instructions provided in the protocol are based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331, EURAMOS 1. The COG recommend changes in the hydration and the rescue frequency and/or dose to be done if pre-specified toxicities of different severity grades occur.
Measured: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
The severity of AEs have been done using NCI CTCAE v4.0. Total number of AEs per severity grade are presented for all AEs and for AEs related to MTX. For AEs related to MTX the number of AEs occurring per preferred term and severity grade are detailed.The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Measured: From the start of HDMTX administration through 8 days post dose for all 4 courses of HDMTX in total
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2013 (estimated)
- Study startDec 2013
- Primary completion3 Jan 2017
- Study completion3 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isofol Medical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mikael Eriksson, MD PhD, Principal investigator, Department of Oncology, Skåne University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01987102
- Sponsor's protocol ID
- ISO-MTX-003
- Status last verified
- Sep 2020
- First submitted
- 5 Nov 2013
- Last updated
- 25 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter, Phase I/II Clinical Trial to Identify the Modufolin® Dose With Most Favorable Safety Prospect and Confirmed Ability to Mitigate High-Dose Methotrexate Induced Toxicity During Treatment of Osteosarcoma Patients
- ClinicalTrials.gov ID
- NCT01987102
- Acronym / sponsor ID
- ISO-MTX-003
- Conditions
- Osteosarcoma
- Keywords
- Methotrexate, Rescue treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Isofol Medical ABIndustry (pharma, biotech, devices)
- Study start
- Dec 2013 (actual)
- Primary completion
- 3 Jan 2017 (actual)
- Study completion
- 3 Jan 2017 (actual)
- First posted
- 19 Nov 2013 (estimated)
- Results
- Posted 26 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, multicenter, phase I/II clinical trial to identify the [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) dose with most favorable safety prospect and confirmed ability to mitigate high-dose methotrexate induced toxicity during treatment of osteosarcoma patients
Detailed description
This is a non-blinded, multicenter, exploratory study in osteosarcoma patients. The study focuses on the overall safety of the HDMTX courses given within a Methotrexate, Adriamycin (doxorubin) and cisPlatin (MAP) treatment schedule, which is closely related to the efficacy of the concomitantly administered folate rescue treatment. Additionally the study aimes to collect pharmacokinetic (PK) profiles of metotrexate (MTX) in serum, of folate metabolites in plasma and to decide the Modufolin® dose to use in future studies.
Patients are enrolled in the study at the first, third or the fifth HDMTX course in a MAP treatment schedule and receive folate rescue therapy according to a strategy based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331.
Folate rescue treatment with Calcium Folinate (SOC) or Modufolin® (MOD) commence 24 h after start of HDMTX administration and then every 6 h until the serum MTX levels are ≤0.1 μmol/L. In case delayed MTX elimination occurs with significant increase in S-creatinine and/or occurrence of oral mucositis or signs of hypo cellular bone marrow, the folate rescue dose and/or the administered hydration will be adjusted in accordance with the COG based MTX toxicity management recommendations.
All patients receives SOC (15 mg/m2) in the first 2 HDMTX courses and MOD in the following 2 courses. Patients are enrolled in one of two MOD dose cohorts: Cohort 1 (15 mg/m2) and Cohort 2 (30 or 7.5 mg/m2 depending on outcome of Cohort 1). Only patients with successful advancements from the first 2 HDMTX courses with Calcium Folinate are allowed to continue with MOD as rescue in the following MAP cycle.
Safety data will be reviewed by an independent board, Data and Safety Monitoring Board (DSMB) that will assess each patient and made recommendations regarding the enrolment of subsequent patients. Furthermore, the DSMB will make a dose level recommendation for Cohort 2 and also a recommendation whether younger children may be allowed in this cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Calcium Folinate, Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)1 MAP cycle (incl. 2 HDMTX Courses using Calcium Folinate rescue 15mg/m2) 1 MAP cycle (incl. 2 HDMTX Courses using [6R] 5,10-methylenetetrahydrofolate rescue 15mg/m2) |
| Cohort 2 | Experimental | Drug: Calcium Folinate, Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)1 MAP cycle (incl. 2 HDMTX Courses using Calcium Folinate rescue 15mg/m2) 1 MAP cycle (incl. 2 HDMTX Courses using [6R] 5,10-methylenetetrahydrofolate rescue 7,5mg/m2 or 30mg/m2*) *Dose will depend on outcome from Cohort 1 |
Who may qualify
- Ages
- 6 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Involvement in another clinical trial within 30 days before enrolment in the study.
- Hypersensitivity to Calcium Folinate.
- Previous treatment with glucarpidase.
- 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
- Patients, who were included in the study in accordance with the inclusion criteria above, must have received 2 adjacent courses of HDMTX with SOC rescue according to the MAP treatment schedule in accordance with this study protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Calcium FolinateAlso: LeucovorinThe enrolled patients will be treated according to the MAP schedule and will receive the study drug Calcium Folinate commencing 24 hours after the administration of HDMTX and then every 6 hours (q6h) thereafter until the S-MTX levels are ≤ 0.1 µmol/L, in accordance with COG management recommendations. All patients will receive standard o care (SOC) in the two (2) first HDMTX courses and [6R] 5,10-methylenetetrahydrofolate in the two (2) following courses. Patients will be enrolled in two (2) [6R] 5,10-methylenetetrahydrofolate dose cohort groups: with [6R] 5,10-methylenetetrahydrofolate start dose of 15 mg/m2 (i.e. the same as for SOC rescue) the first cohort will be administered, and 7.5 or 30 mg/m2 in the second cohort. | Drug | Cohort 1, Cohort 2 |
| [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)Also: Modufolin, arfolitixorinThe enrolled patients will be treated according to the MAP schedule and will receive the study drug [6R] 5,10-methylenetetrahydrofolate commencing 24 hours after the administration of HDMTX and then every 6 hours (q6h) thereafter until the S-MTX levels are ≤ 0.1 µmol/L, in accordance with COG management recommendations. All patients will receive standard o care (SOC) in the two (2) first HDMTX courses and [6R] 5,10-methylenetetrahydrofolate in the two (2) following courses. Patients will be enrolled in two (2) [6R] 5,10-methylenetetrahydrofolate® dose cohort groups: with [6R] 5,10-methylenetetrahydrofolate start dose of 15 mg/m2 (i.e. the same as for SOC rescue) the first cohort will be administered, and 7.5 or 30 mg/m2 in the second cohort. | Drug | Cohort 1, Cohort 2 |
Primary outcome
Number of AEs Per Severity (All Courses)
Time frame: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total
Characterization (number and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Number of HDMTX Related AEs Per Severity (All Courses)
Time frame: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Number of Ongoing AEs Per HDMTX Course
Time frame: From the start of HDMTX administration through 8 days post dose for each course of HDMTX
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Number of Ongoing HDMTX Related AEs Per HDMTX Course
Time frame: From the start of HDMTX administration through 8 days post dose for each course of HDMTX
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
10 secondary outcomes
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Time frame: 8 days after start of first and/or second HDMTX course in a MAP cycle
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.
Time frame: 8 days after start of first HDMTX course in a MAP cycle
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.
Time frame: 8 days after start of second HDMTX course in a MAP cycle
Time to Successful MTX Elimination (Definition C)
Time frame: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Time frame: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Time frame: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Time frame: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Time frame: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Time frame: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Time frame: From the start of HDMTX administration through 8 days post dose for all 4 courses of HDMTX in total
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Pheochromocytoma, Paraganglioma
RecruitingPhase 2
Iscador® P (Mistletoe) Immunotherapy for Recurrent Resectable Osteogenic Sarcoma
Osteogenic Sarcoma Recurrent
RecruitingPhase 2
The CATSINDO Trial - Clinical and Translational Study in Newly Diagnosed Osteosarcoma
Osteosarcoma in Children, Osteosarcoma in Adolescents and Young Adults
RecruitingPhase 2
Evaluating Efficacy of B7-H3-CAR T Cells Administered at the End of Upfront Map Chemotherapy in Patients With Newly Diagnosed High-Risk Osteosarcoma
Pediatric Osteosarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikael Eriksson, MD PhD principal investigator
Department of Oncology, Skåne University Hospital
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Calcium Folinate and [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) in people with Osteosarcoma, run by Isofol Medical AB at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Czechia, Hungary, Poland, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of AEs Per Severity (All Courses) (time frame: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2020.