Ignite Creation Date:
2024-05-05 @ 11:59 PM
Last Modification Date:
2024-10-26 @ 10:43 AM
Study NCT ID:
NCT01469975
Status:
TERMINATED
Last Update Posted:
2017-05-17
First Post:
2011-11-03
Brief Title:
First in Man Study Investigating the Biodistribution the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10
Sponsor:
Centre Leon Berard
Organization:
Centre Leon Berard
Study Overview
Official Title:
First in Man Study Investigating the Biodistribution the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10 FZD10 in Patients With Relapsed or Refractory Non Resectable Synovial Sarcomas
Status:
TERMINATED
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Too slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SYNFRIZZ
Brief Summary:
Advanced synovial sarcoma represents an unmet medical need The gene encoding frizzled homologue 10 FZD10 a 7-transmenbrane receptor member of the Wnt signalling receptor family is overexpressed in SS and is undetectable in normal human tissues except placenta
OncoTherapy Science Inc has developed a chimeric humanized monoclonal antibody mAb against FZD10 named OTSA101 Non-radiolabeled OTSA101 antibody has only weak antagonistic activity on SS cell growth However Yttrium 90-radiolabeled OTSA101 OTSA101-DTPA-90Y showed significant antitumor activity following a single intravenous injection in mouse xenograft model
This first in man clinical trial Phase I in relapsing SS patients resistant to Doxorubicin and ifosfamide will be divided in 2 parts
In Part 1 imaging part using OTSA101 radiolabelled with Indium 111 111In the biodistribution and tumor uptake of OTSA101-DTPA-111In will be followed using 111In as radiotracer
In Part 2 therapeutic part with OTSA101 radiolabelled with Yttrium 90 90Y the safety and PK profiles of OTSA101-DTPA-90Y will be determined and preliminary efficacy data will be collected
This first in Man study should allow defining the optimal recommended dose of OTSA101-DTPA-90Y
Patients will be followed during 1 year
OncoTherapy Science Inc has developed a chimeric humanized monoclonal antibody mAb against FZD10 named OTSA101 Non-radiolabeled OTSA101 antibody has only weak antagonistic activity on SS cell growth However Yttrium 90-radiolabeled OTSA101 OTSA101-DTPA-90Y showed significant antitumor activity following a single intravenous injection in mouse xenograft model
This first in man clinical trial Phase I in relapsing SS patients resistant to Doxorubicin and ifosfamide will be divided in 2 parts
In Part 1 imaging part using OTSA101 radiolabelled with Indium 111 111In the biodistribution and tumor uptake of OTSA101-DTPA-111In will be followed using 111In as radiotracer
In Part 2 therapeutic part with OTSA101 radiolabelled with Yttrium 90 90Y the safety and PK profiles of OTSA101-DTPA-90Y will be determined and preliminary efficacy data will be collected
This first in Man study should allow defining the optimal recommended dose of OTSA101-DTPA-90Y
Patients will be followed during 1 year
Detailed Description:
PART 1 Imaging with OTSA101 DTPA-111In OTSA101-DTPA-111In 15mg OTSA101-DTPA radiolabeled with 185 MBq of 11In will be administered intravenously IV as a single injection on Day -28 D-28 Patients will undergo serial anterior-posterior gamma scans and single photon emission computed tomography SPECTCT at 1 5 24 48 72 144 hours post-dosing to estimate absorbed radiation doses to tumor to normal organs ie liver lung kidney and bone marrow and whole body in order to determine OTSA101-DTPA-111In tumor uptake IDg of injected dose ID per gram of tumor and biodistribution ratio tumornormal tissue of estimated radiation-absorbed dose PK sampling will be performed at the same time points with additional sampling at D-14 and D0
A Steering Committee meeting is planned at the end of PART 1 for each patient The Steering Committee will evaluate on a case by case basis at Day -7 for each patient if heshe can proceed to the therapeutic part based on tumor targeting biodistribution safety and clinical assessments
Patients with expected biodistribution and tumor uptake no safety concerns and no overt signs of disease progression will proceed to the therapeutic part of the study after validation by the Steering Committee
Patients displaying abnormalunexpected biodistribution of OTSA101-DTPA-111In safety concerns andor overt sign of disease progression will be taken off the study and other therapeutic plan will be envisaged
PART 2 Therapeutic dose of OTSA101-DTPA-90Y OTSA101-DTPA-90Y will be administered IV as a single injection on Day 0 ie 14 days after the injection of OTSA101-DTPA-111In - A 1week-delay ie 7 days is authorized from the planned D0
Twelve 12 patients should be randomized in the PART 2 and treated with OTSA101-DTPA-90Y at two initial dose levels 6 patients per dose level
Arm A 15 mg of OTSA101-DTPA radiolabeled with 370MBq of 90Y Dose level 1 DL1
Arm B 15 mg of OTSA101-DTPA radiolabeled with 1110 MBq of 90Y Dose level 2 DL2
Based on safety and preliminary efficacy data a third dose level will be evaluated in 6 additional patients
Arm C 3 mg of OTSA101-DTPA radiolabeled with 2220 MBq of 90Y Dose level 3 DL3
Such a study design will allow the determination of an optimal and recommended dose surrounded by a lower suboptimal dose and a higher maximal tolerated or possibly toxic dose
The first 3 patients will be enrolled at Centre Léon Bérard Following the randomization of the first 2 patients the accrual will be stopped for a maximal period of 1 month The safety data will be reviewed every 2 randomized patients Thee benefitrisk ratio will be regularly reviewed by the iDSMB and the Steering Committee See Section Study Committee
A compassionate program is planned for all randomized patients who derive clinical benefit from the study drug at least stable disease and acceptable tolerance A maximum of 4 injections per year will be planned Subsequent injection will be performed provided that the eligibility criteria except criteria related to previous treatment are met before the day of administration All inclusion in the compassionate program will be validated by the Steering Committee
A Steering Committee meeting is planned at the end of PART 1 for each patient The Steering Committee will evaluate on a case by case basis at Day -7 for each patient if heshe can proceed to the therapeutic part based on tumor targeting biodistribution safety and clinical assessments
Patients with expected biodistribution and tumor uptake no safety concerns and no overt signs of disease progression will proceed to the therapeutic part of the study after validation by the Steering Committee
Patients displaying abnormalunexpected biodistribution of OTSA101-DTPA-111In safety concerns andor overt sign of disease progression will be taken off the study and other therapeutic plan will be envisaged
PART 2 Therapeutic dose of OTSA101-DTPA-90Y OTSA101-DTPA-90Y will be administered IV as a single injection on Day 0 ie 14 days after the injection of OTSA101-DTPA-111In - A 1week-delay ie 7 days is authorized from the planned D0
Twelve 12 patients should be randomized in the PART 2 and treated with OTSA101-DTPA-90Y at two initial dose levels 6 patients per dose level
Arm A 15 mg of OTSA101-DTPA radiolabeled with 370MBq of 90Y Dose level 1 DL1
Arm B 15 mg of OTSA101-DTPA radiolabeled with 1110 MBq of 90Y Dose level 2 DL2
Based on safety and preliminary efficacy data a third dose level will be evaluated in 6 additional patients
Arm C 3 mg of OTSA101-DTPA radiolabeled with 2220 MBq of 90Y Dose level 3 DL3
Such a study design will allow the determination of an optimal and recommended dose surrounded by a lower suboptimal dose and a higher maximal tolerated or possibly toxic dose
The first 3 patients will be enrolled at Centre Léon Bérard Following the randomization of the first 2 patients the accrual will be stopped for a maximal period of 1 month The safety data will be reviewed every 2 randomized patients Thee benefitrisk ratio will be regularly reviewed by the iDSMB and the Steering Committee See Section Study Committee
A compassionate program is planned for all randomized patients who derive clinical benefit from the study drug at least stable disease and acceptable tolerance A maximum of 4 injections per year will be planned Subsequent injection will be performed provided that the eligibility criteria except criteria related to previous treatment are met before the day of administration All inclusion in the compassionate program will be validated by the Steering Committee
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ET11-062 | OTHER | Sponsor number | None |
| 2011-002574-23 | EUDRACT_NUMBER | None | None |