Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06630624
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-06
Brief Title:
Dose Finding Efficacy and Immunological Response of IP-001 Following RFA MWA or IRE for CRLM
Sponsor:
None
Organization:
None
Study Overview
Official Title:
INJECTABL-II Dose Finding Efficacy and Immunological Response of a Novel Immuno-Adjuvant IP-001 Following Radiofrequency Ablation Microwave Ablation or Irreversible Electroporation for Colorectal Liver Metastases
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INJECTABL-II
Brief Summary:
The primary objectives of this phase III prospective clinical trial are to assess the optimal dose efficacy safety and immunological effect of ablation and intra-tumoral injection of a novel immuno-adjuvant IP-001 for colorectal liver metastases CRLM The study consists of three parts devided into two phases
Phase 1 is a dose-escalation study according to a classic 33 design to identify the dose level at which IP-001 exhibits an acceptable level of toxicity following microwave ablation MWA of CRLM in refractory metastatic colorectal cancer CRC patients
Phase 2 part 1 and part 2 are performed simultaneously In phase 2 part 1 a single arm study assesses the efficacy of IP-001 following MWA for CRLM for curative intent In phase 2 part 2 a randomized 3-armed study assesses the efficacy and immunomodulation of IP-001 following three ablative modalities arm A radiofrequency ablation RFA arm B MWA and arm C irreversible electroporation IRE for CRLM in refractory metastatic CRC patients
Phase 1 is a dose-escalation study according to a classic 33 design to identify the dose level at which IP-001 exhibits an acceptable level of toxicity following microwave ablation MWA of CRLM in refractory metastatic colorectal cancer CRC patients
Phase 2 part 1 and part 2 are performed simultaneously In phase 2 part 1 a single arm study assesses the efficacy of IP-001 following MWA for CRLM for curative intent In phase 2 part 2 a randomized 3-armed study assesses the efficacy and immunomodulation of IP-001 following three ablative modalities arm A radiofrequency ablation RFA arm B MWA and arm C irreversible electroporation IRE for CRLM in refractory metastatic CRC patients
Detailed Description:
Rationale As ablative therapies lead to in situ availability of ablated tumor material RFA MWA and IRE have been shown to trigger an anti-tumor immune response However the magnitude of this response seems insufficient to induce a detectable abscopal effect shrinkage or disappearance of distant untreated tumors In recent years there has been a growing interest in exploring the potential synergy between ablative techniques and immune activating strategies to induce a more robust long-term systemic anti-tumor immune response
A novel immuno-adjuvant IP-001 has been developed to address this synergy and trigger a tumor-specific systemic immune response when exposed to liberated tumor antigens following tumor ablation 10 IP-001 for Injection IP-001 is injected in and around the ablation zone immediately following ablation IP-001 creates a depot of released tumor antigens after ablation and drives a potent downstream adaptive immune response against these antigens
The combination of IP-001 with an ablative treatment in patients with CRLM could prove beneficial in terms of improved distant progression free survival PFS and possibly OS
Study design The INJECTABL-II trial is a phase I-II prospective clinical trial The primary conducting center will be the Amsterdam UMC Amsterdam the Netherlands The purpose of this trial is to assess the optimal dose efficacy safety and immunological effect intra-tumoral injection of IP-001 following ablation The trial consists of three study parts divided into two phases In phase 1 a dose-finding study will be conducted followed by two parallel phase 2 studies called phase 2 part 1 and phase 2 part 2
The investigators will first conduct a phase 1 dose-escalation study according to a classic 33 design to determine the maximum tolerated dose MTD of intra-tumoral IP-001 injection following MWA In phase 2 part 1 a single arm study will be performed with the optimal dose found in phase 1 to assess efficacy of intra-tumoral IP-001 injection following MWA in patients with CRLM who will receive ablation for curative intent The investigators hypothesize that MWA IP-001 is superior to MWA alone in terms of 1-year distant progression-free survival DPFS 1-year DPFS will be compared to a matched historical prospective cohort of the COLLISION trial in which 126 patients have been included For the sample size calculation the one-sided Z-Test with pooled variance has been used yielding 59 patients to be included in this phase of the trial MWA IP-001 Phase 2 part 2 will be conducted in parallel as a randomized 3-armed study assessing the efficacy and immunomodulation of intra-tumoral IP-001-injection following three ablative modalities arm A RFA arm B MWA or arm C IRE in patients with refractory metastatic CRC Efficacy of each randomized study arm will be assessed independently and thus a single-group design has been used for the sample size calculations The study treatment is considered effective when a DCR of 25 is reached at 16 weeks A one-sided one-sample Z-test has been used to estimate the standard deviation Bonferroni correction is used to correct for multiple comparisons 21 patients per study arm arm A RFA arm B MWA and arm C IRE will be randomized in phase 2 part 2 of the trial
Study population In phase 1 of the trial patients with refractory metastatic CRC and at least 3 CRLM 1-3 cm will be included In phase 2 part 1 of the trial patients with 1-3 CRLM 3 cm who will receive MWA for curative intent will be included In phase 2 part 2 of the trial patients with refractory liver only or liver dominant metastatic CRC limited extra-hepatic disease and 1-4 CRLM 3 cm eligible for RFA MWA or IRE will be included
Intervention All patients will receive ablation and intra-tumoral injection of IP-001 of CRLM During phase 1 2 CRLM will be treated with intra-tumoral injection of IP-001 following MWA During phase 2 part 1 1-3 CRLM eligble for MWA with curative intent will be treated with intra-tumoral injection of IP-001 following MWA During phase 2 part 2 1-4 CRLM will be treated with intra-tumoral injection of IP-001 following MWA RFA or IRE
A novel immuno-adjuvant IP-001 has been developed to address this synergy and trigger a tumor-specific systemic immune response when exposed to liberated tumor antigens following tumor ablation 10 IP-001 for Injection IP-001 is injected in and around the ablation zone immediately following ablation IP-001 creates a depot of released tumor antigens after ablation and drives a potent downstream adaptive immune response against these antigens
The combination of IP-001 with an ablative treatment in patients with CRLM could prove beneficial in terms of improved distant progression free survival PFS and possibly OS
Study design The INJECTABL-II trial is a phase I-II prospective clinical trial The primary conducting center will be the Amsterdam UMC Amsterdam the Netherlands The purpose of this trial is to assess the optimal dose efficacy safety and immunological effect intra-tumoral injection of IP-001 following ablation The trial consists of three study parts divided into two phases In phase 1 a dose-finding study will be conducted followed by two parallel phase 2 studies called phase 2 part 1 and phase 2 part 2
The investigators will first conduct a phase 1 dose-escalation study according to a classic 33 design to determine the maximum tolerated dose MTD of intra-tumoral IP-001 injection following MWA In phase 2 part 1 a single arm study will be performed with the optimal dose found in phase 1 to assess efficacy of intra-tumoral IP-001 injection following MWA in patients with CRLM who will receive ablation for curative intent The investigators hypothesize that MWA IP-001 is superior to MWA alone in terms of 1-year distant progression-free survival DPFS 1-year DPFS will be compared to a matched historical prospective cohort of the COLLISION trial in which 126 patients have been included For the sample size calculation the one-sided Z-Test with pooled variance has been used yielding 59 patients to be included in this phase of the trial MWA IP-001 Phase 2 part 2 will be conducted in parallel as a randomized 3-armed study assessing the efficacy and immunomodulation of intra-tumoral IP-001-injection following three ablative modalities arm A RFA arm B MWA or arm C IRE in patients with refractory metastatic CRC Efficacy of each randomized study arm will be assessed independently and thus a single-group design has been used for the sample size calculations The study treatment is considered effective when a DCR of 25 is reached at 16 weeks A one-sided one-sample Z-test has been used to estimate the standard deviation Bonferroni correction is used to correct for multiple comparisons 21 patients per study arm arm A RFA arm B MWA and arm C IRE will be randomized in phase 2 part 2 of the trial
Study population In phase 1 of the trial patients with refractory metastatic CRC and at least 3 CRLM 1-3 cm will be included In phase 2 part 1 of the trial patients with 1-3 CRLM 3 cm who will receive MWA for curative intent will be included In phase 2 part 2 of the trial patients with refractory liver only or liver dominant metastatic CRC limited extra-hepatic disease and 1-4 CRLM 3 cm eligible for RFA MWA or IRE will be included
Intervention All patients will receive ablation and intra-tumoral injection of IP-001 of CRLM During phase 1 2 CRLM will be treated with intra-tumoral injection of IP-001 following MWA During phase 2 part 1 1-3 CRLM eligble for MWA with curative intent will be treated with intra-tumoral injection of IP-001 following MWA During phase 2 part 2 1-4 CRLM will be treated with intra-tumoral injection of IP-001 following MWA RFA or IRE
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