Ignite Creation Date:
2024-05-06 @ 1:10 PM
Last Modification Date:
2024-10-26 @ 1:10 PM
Study NCT ID:
NCT03958383
Status:
SUSPENDED
Last Update Posted:
2024-02-14
First Post:
2019-05-07
Brief Title:
IT-hu1418-IL2 With Radiation Nivolumab and Ipilimumab for Melanoma
Sponsor:
University of Wisconsin Madison
Organization:
University of Wisconsin Madison
Study Overview
Official Title:
Phase III Intratumoral Administration of Hu1418-IL2 With Local Radiation Nivolumab and Ipilimumab in Subjects With Advanced Melanoma
Status:
SUSPENDED
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Administrative
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial is designed to determine the maximum tolerated dose or the maximum administered dose of intratumoral administration of hu1418-IL2 and to evaluate side effects of intratumoral hu1418-IL2 when given alone after radiation therapy after radiation therapy and in combination with nivolumab and after radiation therapy and in combination with nivolumab and ipilimumab in patients with melanoma that is advanced stage IV or with melanoma that cannot be removed by surgery and is considered surgically incurable Hu1418-IL2 is a molecule called a fusion protein that can bind to some tumor cells and cause immune cells to become activated to kill tumor cells Radiation therapy is a type of cancer treatment that uses beams of high energy x-rays to kill tumor cells and shrink tumors Immunotherapy with immune checkpoint inhibitors such as nivolumab and ipilimumab can help the bodys immune system attack cancer by releasing the brakes on the immune system to allow cancer fighting immune cells to remain activated This study will evaluate whether giving intratumoral hu1418-IL2 with radiation therapy nivolumab and ipilimumab has antitumor activity for participants with advanced melanoma
After completion of study treatment participants are followed up at 30 days every 12 weeks for up to 2 years and then every 6 months thereafter
After completion of study treatment participants are followed up at 30 days every 12 weeks for up to 2 years and then every 6 months thereafter
Detailed Description:
PRIMARY OBJECTIVES
I Determine the maximum tolerated dose MTD or maximum administered dose MAD of intratumoral IT-Hu1418-IL2 fusion protein hu1418-IL2 in subjects with advanced melanoma Phase IA
II Evaluate the safety and tolerability of IT-hu1418-IL2 when given alone Phase IA
III Determine the maximum tolerated dose MTD or maximum administered dose MAD of IT-hu1418-IL2 after receiving palliative radiation therapy RT in subjects with advanced melanoma Phase IB
IV Evaluate the safety and tolerability of the combination of palliative RT with IT-hu1418-IL2 Phase IB
V Determine the maximum tolerated dose MTD or maximum administered dose MAD of IT-hu1418-IL2 after receiving palliative RT and in combination with nivolumab in subjects with advanced melanoma Phase IC
VI Evaluate the safety and tolerability of the combination of palliative RT nivolumab and IT-hu1418-IL2 Phase IC
VII Determine the maximum tolerated dose MTD or maximum administered dose MAD of IT-hu1418-IL2 after receiving palliative RT and in combination with nivolumab and ipilimumab in subjects with advanced melanoma Phase ID
VIII Evaluate the safety and tolerability of the combination of palliative RT nivolumab ipilimumab and IT-hu1418-IL2 Phase ID
IX Evaluate local and systemic objective tumor responses to treatment with IT-hu1418-IL2 in combination with palliative RT nivolumab and ipilimumab Phase ID
SECONDARY OBJECTIVES
I Evaluate progression-free survival PFS overall survival OS clinical benefit CB defined as complete response CR partial response PR stable disease SD and duration of response to hu1418-IL2 in combination with RT nivolumab and ipilimumab
II Evaluate pathologic tissue evidence of immune response at the injection site and untreated sites
III Evaluate PFS CB and duration of response to hu1418-IL2 in combination with palliative RT nivolumab and ipilimumab based on resistance to prior treatment with anti-CTLA-4 andor anti PD1PD-L1 antibody
IV Evaluate serial serum samples to determine the pharmacokinetics of hu1418-IL2 administered intratumorally
V Evaluate each subjects tumor cells for expression of GD2 and PD-L1 and determine if either antitumor activity or selected treatment-associated biologic effects are more likely for tumors that are GD2 then GD2- and PD-L1 than PD-L1-
VI Evaluate whether PD-L1 expression is induced or augmented from baseline following initiation of treatment by comparing serial biopsies
VII Evaluate the immunologic activation induced in vivo by IT-hu1418-IL2 addressed by in vitro cellular serologic and flow cytometry immune assays
VIII Evaluate for histological evidence of antitumor activity based on the presence of necrotic tumor cells inflammatory infiltrate cellular phenotype of infiltrate and presence of hu1418-IL2 within the tumor at selected post-treatment timepoints
IX Evaluate circulating tumor cells exosomes endogenous antibodies andor deoxyribonucleic acid DNA as exploratory biomarkers associated with clinical response to IT-hu1418-IL2 in combination with RT nivolumab and ipilimumab
X Evaluate serial peripheral blood mononuclear cell PBMC samples to monitor the induction of T cell responses to melanoma-associated antigens
XI Evaluate objective tumor responses both locally and systemically by immune-related response criteria in Phases IA IB and IC of this trial involving IT-hu1418-IL2 alone and in combinations with palliative RT and with palliative RT and nivolumab respectively
OUTLINE This is a dose escalation study of hu1418-IL2 fusion protein
PHASE IA Participants receive hu1418-IL2 fusion protein intratumorally IT once daily QD on days 1-3 Treatment repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity A total of 9-18 participants will be enrolled in 3 escalating dose levels to determine the Maximum Tolerated Dose MTDMaximum Administered Dose MAD of hu1418-IL2 in Phase IA
PHASE IB Participants undergo palliative RT on days -8 to -4 of cycle 1 only Participants also receive hu1418-IL2 fusion protein IT as in phase IA Treatment with hu1418-IL2 repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity The MTDMAD of IT-hu1418-IL2 following palliative RT will be determined starting 1 dose level below the Phase IA determined MTDMAD of IT-hu1418-IL2 up to the Phase IA determined MTDMAD
PHASE IC Participants undergo palliative RT on days -8 to -4 of cycle 1 only Nivolumab 3 mgkg is given every 2 weeks for up to 1 year with the initial dose given between day -7 and day -1 of cycle 1 Participants also receive hu1418-IL2 fusion protein IT as in phase IA Treatment with hu1418-IL2 repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity The MTDMAD of IT-hu1418-IL2 following palliative RT in combination with nivolumab will be determined starting 1 dose level below the Phase IB determined MTDMAD of IT-hu1418-IL2 up to the Phase IB determined MTDMAD
PHASE ID Participants undergo palliative RT on days -8 to -4 of cycle 1 only Nivolumab 1 mgkg in combination with ipilimumab 3 mgkg is given every 3 weeks for 4 cycles with the initial dose given between day -7 and day -1 of cycle 1 Following 4 cycles no additional ipilimumab will be administered Following cycle 4 maintenance nivolumab 3 mgkg can be given for up to one year Participants also receive hu1418-IL2 fusion protein IT as in phase IA Treatment with hu1418-IL2 repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity The MTDMAD of IT-hu1418-IL2 following palliative RT in combination with nivolumab and ipilimumab will be determined starting 1 dose level below the Phase IC determined MTDMAD of IT-hu1418-IL2 up to the Phase IC determined MTDMAD A total of 28 participants will be enrolled at the Phase ID MTDMAD of IT-hu1418-IL2
I Determine the maximum tolerated dose MTD or maximum administered dose MAD of intratumoral IT-Hu1418-IL2 fusion protein hu1418-IL2 in subjects with advanced melanoma Phase IA
II Evaluate the safety and tolerability of IT-hu1418-IL2 when given alone Phase IA
III Determine the maximum tolerated dose MTD or maximum administered dose MAD of IT-hu1418-IL2 after receiving palliative radiation therapy RT in subjects with advanced melanoma Phase IB
IV Evaluate the safety and tolerability of the combination of palliative RT with IT-hu1418-IL2 Phase IB
V Determine the maximum tolerated dose MTD or maximum administered dose MAD of IT-hu1418-IL2 after receiving palliative RT and in combination with nivolumab in subjects with advanced melanoma Phase IC
VI Evaluate the safety and tolerability of the combination of palliative RT nivolumab and IT-hu1418-IL2 Phase IC
VII Determine the maximum tolerated dose MTD or maximum administered dose MAD of IT-hu1418-IL2 after receiving palliative RT and in combination with nivolumab and ipilimumab in subjects with advanced melanoma Phase ID
VIII Evaluate the safety and tolerability of the combination of palliative RT nivolumab ipilimumab and IT-hu1418-IL2 Phase ID
IX Evaluate local and systemic objective tumor responses to treatment with IT-hu1418-IL2 in combination with palliative RT nivolumab and ipilimumab Phase ID
SECONDARY OBJECTIVES
I Evaluate progression-free survival PFS overall survival OS clinical benefit CB defined as complete response CR partial response PR stable disease SD and duration of response to hu1418-IL2 in combination with RT nivolumab and ipilimumab
II Evaluate pathologic tissue evidence of immune response at the injection site and untreated sites
III Evaluate PFS CB and duration of response to hu1418-IL2 in combination with palliative RT nivolumab and ipilimumab based on resistance to prior treatment with anti-CTLA-4 andor anti PD1PD-L1 antibody
IV Evaluate serial serum samples to determine the pharmacokinetics of hu1418-IL2 administered intratumorally
V Evaluate each subjects tumor cells for expression of GD2 and PD-L1 and determine if either antitumor activity or selected treatment-associated biologic effects are more likely for tumors that are GD2 then GD2- and PD-L1 than PD-L1-
VI Evaluate whether PD-L1 expression is induced or augmented from baseline following initiation of treatment by comparing serial biopsies
VII Evaluate the immunologic activation induced in vivo by IT-hu1418-IL2 addressed by in vitro cellular serologic and flow cytometry immune assays
VIII Evaluate for histological evidence of antitumor activity based on the presence of necrotic tumor cells inflammatory infiltrate cellular phenotype of infiltrate and presence of hu1418-IL2 within the tumor at selected post-treatment timepoints
IX Evaluate circulating tumor cells exosomes endogenous antibodies andor deoxyribonucleic acid DNA as exploratory biomarkers associated with clinical response to IT-hu1418-IL2 in combination with RT nivolumab and ipilimumab
X Evaluate serial peripheral blood mononuclear cell PBMC samples to monitor the induction of T cell responses to melanoma-associated antigens
XI Evaluate objective tumor responses both locally and systemically by immune-related response criteria in Phases IA IB and IC of this trial involving IT-hu1418-IL2 alone and in combinations with palliative RT and with palliative RT and nivolumab respectively
OUTLINE This is a dose escalation study of hu1418-IL2 fusion protein
PHASE IA Participants receive hu1418-IL2 fusion protein intratumorally IT once daily QD on days 1-3 Treatment repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity A total of 9-18 participants will be enrolled in 3 escalating dose levels to determine the Maximum Tolerated Dose MTDMaximum Administered Dose MAD of hu1418-IL2 in Phase IA
PHASE IB Participants undergo palliative RT on days -8 to -4 of cycle 1 only Participants also receive hu1418-IL2 fusion protein IT as in phase IA Treatment with hu1418-IL2 repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity The MTDMAD of IT-hu1418-IL2 following palliative RT will be determined starting 1 dose level below the Phase IA determined MTDMAD of IT-hu1418-IL2 up to the Phase IA determined MTDMAD
PHASE IC Participants undergo palliative RT on days -8 to -4 of cycle 1 only Nivolumab 3 mgkg is given every 2 weeks for up to 1 year with the initial dose given between day -7 and day -1 of cycle 1 Participants also receive hu1418-IL2 fusion protein IT as in phase IA Treatment with hu1418-IL2 repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity The MTDMAD of IT-hu1418-IL2 following palliative RT in combination with nivolumab will be determined starting 1 dose level below the Phase IB determined MTDMAD of IT-hu1418-IL2 up to the Phase IB determined MTDMAD
PHASE ID Participants undergo palliative RT on days -8 to -4 of cycle 1 only Nivolumab 1 mgkg in combination with ipilimumab 3 mgkg is given every 3 weeks for 4 cycles with the initial dose given between day -7 and day -1 of cycle 1 Following 4 cycles no additional ipilimumab will be administered Following cycle 4 maintenance nivolumab 3 mgkg can be given for up to one year Participants also receive hu1418-IL2 fusion protein IT as in phase IA Treatment with hu1418-IL2 repeats every 21 days for cycles 1-4 Participants who are eligible may continue to receive hu1418-IL2 fusion protein maintenance therapy QD on days 1-3 beginning with cycle 5 Maintenance cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity The MTDMAD of IT-hu1418-IL2 following palliative RT in combination with nivolumab and ipilimumab will be determined starting 1 dose level below the Phase IC determined MTDMAD of IT-hu1418-IL2 up to the Phase IC determined MTDMAD A total of 28 participants will be enrolled at the Phase ID MTDMAD of IT-hu1418-IL2
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| Protocol Version 7302020 | OTHER | UW Madison | httpsreporternihgovquickSearchR35CA197078 |
| 2017-1464 | OTHER | None | None |
| R35CA197078 | NIH | None | None |
| A534260 | OTHER | None | None |
| SMPHMEDICINEHEM-ONC | OTHER | None | None |