Colorectal CancerPhase 1/2INJECTABL-IINCT06630624
Dose Finding, Efficacy and Immunological Response of IP-001 Following MWA or IRE for CRLM
A Phase 1/2 study testing IP-001 in people with Colorectal Cancer and Liver Metastases, run by M.R. Meijerink at 1 site in Netherlands.
Trial summary
The primary objectives of this phase I/II, 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Liver Metastases, Liver Metastasis Colon Cancer
- What is being tested?
- IP-001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Jul 2024to 1 Aug 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Measurable metastatic CRC based on RECIST v1.1;
- The primary tumor has been resected before study inclusion or the patient is asymptomatic with respect to the in situ primary tumor;
- Last imaging ≤ 4 weeks prior to the on-study ablative procedure;
- Age ≥ 18 years;
- Eastern Cooperative Oncology Group (ECOG) performance status of no more than 1;
- A life expectancy of at least 3 months at the time of inclusion;
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- Adequate bone marrow, liver, and renal function as assessed by laboratory tests. These results should be judged by the local investigator and should be conducted within 7 days prior to definite inclusion;
- Written informed consent.
- Progressive or stable metastatic CRC on CT-scan after at least 1 lines of standard of care systemic treatment. Standard of care systemic treatment will be defined and determined by the treating oncologist. A summary of standard of care systemic treatment for CRLM as used by the medical oncologists at Amsterdam UMC has been listed in Table 1. Patients can also be included if systemic treatment has to be terminated due to toxicity or when patients refuse (further) systemic treatment, or when patients are in a therapy break from systemic therapy as patients can continue with further systemic treatment one month after the study treatment;
- At least 2 CRLM eligible for MWA with a minimum diameter of 1cm and a maximum diameter of 3cm and one (optional but not required) CRLM that will be left untreated and is eligible for biopsy;
- No limitations on intrahepatic or extrahepatic disease;
- At least one CRLM and a maximum of three CRLM size ≤ 3 cm eligible for MWA with curative intent;
- Additional unablatable CRLM should be resectable with a maximum of 10 additional CRLM;
- Resectability and ablatability should be re-confirmed intra-operatively by US in case of combined/staged resection and ablation. Intra-operatively also full exploration for hepatic, peritoneal and regional lymph node metastases should be performed;
- Liver only or liver dominant measurable metastatic CRC based on RECIST v1.1;
- Liver dominant metastatic disease is defined as the hepatic tumorload (number and estimated volume) exceeding the extrahepatic tumorload, with a maximum of 5 unequivocal extrahepatic metastases in ≤2 different organ systems;
- At least 2 CRLM, of which at least one is eligible for the study treatment (RFA, MWA and IRE);
- At least 50% (number and estimated volume) of the CRLM should be eligible for ablation. A maximum of 4 CRLM can be assigned for the study treatment. One CRLM has to be left untreated;
- At least one untreated CRLM and one 'to-be-treated' CRLM should be eligible for biopsy;
- Maximum size of CRLM for study treatment is 3cm;
- Any CRLM with a maximum lesion size of 5cm at time of inclusion;
- Limited extrahepatic disease, restricted to the lungs and lymph nodes, with a maximum lesion size of 3cm at time of inclusion. See below for additional information regarding pulmonary nodules;
- Progressive disease on CT-scan after standard of care systemic treatment. Standard of care systemic treatment will be defined and determined by the treating oncologist. Patients can also be included if systemic treatment has to be terminated due to toxicity or when patients refuse (further) systemic treatment.;
Who cannot join
- Compromised liver function defined as warning signs of portal hypertension, INR \> 1,5 without use of anticoagulants, bilirubin \> x 1.5 Upper limit of normal range (ULN) ASAT \>5.0 x ULN, ALAT \>5.0 x ULN.
- Compromised kidney function defined as eGFR \<45 ml/min (using the Cockcroft Gault formula);
- Active autoimmune disease requiring disease-modifying therapy at the time of screening or during the study period: i.e. \> 10 mg prednisolone per day or other immunosuppressive therapy (e.g. methotrexate);
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results;
- Known allergic reaction to shellfish, crabs, crustaceans, or any trial components;
- Known history of HIV or active Hepatitis C or Hepatitis B infection;
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- Uncontrolled infections (\> grade 2 NCI-CTC version 3.0); requiring antibiotics;
- Pregnant or breast-feeding subjects; Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment;
- Known allergy to contrast agent that cannot be adequately prevented;
- Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study;
- Major surgery or radiotherapy ≤ 3 weeks (7 days for single fraction of palliative radiotherapy) prior to the on-study ablative procedure;
- Systemic therapy ≤ 4 weeks prior to the on-study ablative procedure;
- CTCAE Grade ≥1 from all side effects of prior therapies or prior procedures at the time of inclusion.
- Phase 1
- No additional exclusion criteria.
- Phase 2 part 1:
- Radical treatment unfeasible or unsafe (e.g. insufficient FLR);
- The presence of extrahepatic nodal or non-nodal metastases. One locally treatable lung metastasis is allowed;
- Any surgical resection or focal ablative liver therapy for CRLM prior to inclusion;
- Phase 2 part 2:
- Tumor diameter of ≥ 5 cm of any hepatic lesion at the time of inclusion. If lesion size exceeds 5 cm at start of the procedure, the patient will not be excluded;
- Metastases in the lungs or lymph nodes ≥ 3 cm. If lesion size exceeds 3 cm at start of the procedure, the patient will not be excluded;
- Metastases in any other organ than the liver, lungs of lymph nodes;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC - location VUmc
Amsterdam, North Holland, 1118 HV
Danielle J. Vos, MD, 020-44571 ext. +31, interventieradiologie@amsterdamumc.nl
Martijn R. Meijerink, Prof.
About this study
Official title: INJECTABL-II: Dose Finding, Efficacy and Immunological Response of a Novel Immuno-Adjuvant (IP-001) Following Microwave Ablation or Irreversible Electroporation for Colorectal Liver Metastases.
The primary objectives of this phase I/II, 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 '3+3' 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, two-armed study assesses the efficacy and immunomodulation of IP-001 following two ablative modalities: arm A (MWA) and arm C (irreversible electroporation (IRE)) for CRLM in refractory metastatic CRC patients.
Read the detailed description
Rationale: As ablative therapies lead to in situ availability of ablated tumor material, 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. 1.0% 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 '3+3' 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, two-armed study assessing the efficacy and immunomodulation of intra-tumoral IP-001-injection following three ablative modalities (arm A (MWA) or arm C (IRE)) in patients with 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 (MWA) and arm B (IRE)) will be randomized in phase 2 part 2 of the trial.
Study population: : In phase 1 of the trial, patients with metastatic CRC and at least 2 CRLM (1-3 cm) that have received at least 1 line of systemic therapy 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 MWA and 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 or IRE.
- Being tested
- IP-001
- Keywords
- Colorectal liver metastases, Colorectal hepatic metastases, irreversible electroporation, Microwave ablation, Immunotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IP-001Drug
Intra-tumoral injection of IP-001 following ablation (MWA or IRE).
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose esclatation of IP-001 | Experimental | Intra-tumoral injection of IP-001 following MWA of two pre-defined colorectal liver metastases (CRLM). Patients will receive sequentially higher doses of the IP-001, always divided equally over the two CRLM, regardless of size. Starting dose will be 8 mL and the dose-escalating steps will be 4 mL up to a total of 16 mL per patient. Receives: Drug: IP-001 |
| Phase 2 Part 1 MWA + IP-001 | Experimental | One to three colorectal liver metastases (CRLM) will be treated with MWA followed by intra-tumoral injection of IP-001. Receives: Drug: IP-001 |
| Phase 2 part 2 MWA + IP-001 | Experimental | One to four colorectal liver metastases (CRLM) will be treated with MWA followed by intra-tumoral injection of IP-001. Receives: Drug: IP-001 |
| Phase 2 part 2 IRE + IP-001 | Experimental | One to four colorectal liver metastases (CRLM) will be treated with IRE followed by intra-tumoral injection of IP-001. Receives: Drug: IP-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) (Phase 1)
The highest dose of IP-001 that does not cause unacceptable side effects defined as the dose level below the dose level that caused 2 or more Dose Limiting Toxicites (DLTs).
Measured: During the 10-day DLT-monitoring period.
1-Year Distant Progression Free Survival (DPFS) (Phase 2 part 1)
Overall DPFS is defined as the time from inclusion to the time of disease progression (according to the RECIST 1.1 guideline) or death (events). Death related to other causes is considered a failure event for DPFS.
Measured: 1 year
Disease Control Rate (DCR) (Phase 2 part 2)
DCR is calculated as the percentage of patients experiencing either iSD (Stable Disease), iPR (Partial Response) or iCR (Complete Response) as best response in target lesions at 16 weeks after treatment according to iRECIST.
Measured: 16 weeks
Secondary outcomes (18)
Elimination half-life of the study drug IP-001 in the blood (t1/2 ) (Phase 1 and phase 2 part 2)
Blood samples will be taken prior to and at different timepoints after the procedure for pharmacokinetic analysis defined as elimination half-life of the study drug IP-001 in the blood.
Measured: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Overall Survival (OS; per patient analysis) (All phases)
OS is defined as the time from focal therapy to the time of death due to any cause, assessed up to 5 years;
Measured: Up to 5 years
(Serious) Adverse Events ((S)AEs) (All phases)
(Serious) adverse events according to CTCAE v5.0, assessed up to 5 years.
Measured: Up to 5 years
Duration of best overall response (DoR, per patient analysis) (Phase 2 part 2)
DoR is defined from when the time measurement criteria are first met for CR/iCR or PR/iPR until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years;
Measured: Up to 3 years
Local Tumor Progression Free Survival (LTPFS, per lesion analysis) (All phases)
LTPFS is defined as the time from focal therapy to the time of local tumor progression or death from any cause, whichever occurs first. Local tumor is defined as the treated tumor, assessed up to 5 years.
Measured: Up to 5 years
Distant Progression Free Survival (DPFS; per patient analysis) (All phases)
DPFS is defined as the time from focal therapy to the time of distant disease progression or death from any cause, whichever occurs first, assessed up to 5 years. Distant disease is defined as extra-hepatic lesions and untreated, hepatic lesions;
Measured: Up to 5 years
Hepatic progression free survival (HPFS; per patient analysis) (All phases)
HPFS is defined as the time from focal therapy to the time of progression of any tumor in the liver (treated or untreated) or death from any cause, whichever occurs first, assessed up to 5 years;
Measured: Up to 5 years
Time to progression (TTP; per patient analysis) (All phases)
TTP is defined as the time from focal therapy to the time of unequivocal disease progression (events); the date of death from any cause or death without established RECIST progressive disease is considered to be a competing risk. TTP will be analysed with and without competing risks. Assessed up to 5 years.
Measured: Up to 5 years
Progression-free survival (PFS; per patient analysis) (All phases)
The time until the date of unequivocal disease progression (local site recurrence or metastatic disease) or death from any cause, whichever occurs first, assessed up to 5 years.
Measured: Up to 5 years
Disease-free survival (DFS; per patient analysis) (All phases)
DFS is defined as the time from focal therapy until the appearance or worsening of signs or symptoms of the disease or death from any cause, whichever occurs first, assesed up to 5 years.
Measured: Up to 5 years
Pain assessment (Per procedure analysis)
Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis). Assessed prior to, directly after and every three months after local treatment, and up to 1 year.
Measured: Up to 1 year
Ablative Success (All phases)
Ablative success (or technical success rate) is defined as the primary efficacy rate; the percentage of successfully eradicated tumor tissue after the local treatment, assessed directly after the treatment.
Measured: Directly after treatment
Quality of Life using EORCT QLQ-C30 questionnaireS (QoL; per patient analysis) (Phase 2)
The quality of life is assessed using EORCT QLQ-C30 questionnaires, prior to, and every three months after treatment during a total follow-up time of 1 year.
Measured: 1 year
Quality of Life using EQ-5D questionnaires (QoL; per patient analysis) (Phase 2)
The quality of life is assessed using EQ-5D questionnaires, prior to, and every three months after treatment during a total follow-up time of 1 year.
Measured: 1 year
Quality of Life using PRODISQ questionnaires(QoL; per patient analysis) (Phase 2)
The quality of life is assessed using PRODISQ questionnaires, prior to, and every three months after treatment during a total follow-up time of 1 year.
Measured: 1 year
Time of maximum observed concentration of the study drug IP-001 in the blood (Tmax) (Phase 1 and phase 2 part 2)
Blood samples will be taken prior to and at different timepoints after the procedure for pharmacokinetic analysis defined as time of maximum observed concentration of the study drug IP-001 in the blood.
Measured: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Maximum observed concentration of the study drug IP-001 in the blood (Cmax) (Phase 1 and phase 2 part 2)
Blood samples will be taken prior to and at different timepoints after the procedure for pharmacokinetic analysis defined as maximum observed concentration of the study drug IP-001 in the blood.
Measured: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Area under the curve from time 0 to the time of the last measurable concentration of the study drug IP-001 in the blood (AUC 0-t) (Phase 1 and phase 2 part 2)
Blood samples will be taken prior to and at different timepoints after the procedure for pharmacokinetic analysis defined as the area under the curve from time 0 to the time of the last measurable concentration of the study drug IP-001 in the blood.
Measured: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2024
- Study start10 Jul 2024
- Primary completion1 Aug 2029 (estimated)
- Study completion1 Aug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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
- Model description
- Firstly, a phase 1, dose-escalation study according to a classic '3+3' design will be performed 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 the ablation for curative intent. Phase 2 part 2 will be conducted in parallel to phase 2 part 1 as a randomized, two-armed study assessing the efficacy and immunomodulation of intra-tumoral IP-001-injection following two ablative modalities (arm A (MWA) or arm C (IRE)) in patients with refractory metastatic CRC.
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.R. Meijerink
- Sponsor type
- University, hospital or other
- Collaborators
- Immunophotonics, Inc., Angiodynamics, Inc.
- Responsible party
- Sponsor-investigator, M.R. Meijerink, Amsterdam UMC, location VUmc
- Investigators
- Martijn R. Meijerink, Prof., Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06630624
- Sponsor's protocol ID
- 2024.0610
- Other IDs
- 2023-504572-25-00, 2023
- Acronym
- INJECTABL-II
- Status last verified
- Jun 2025
- First submitted
- 6 Sep 2024
- Last updated
- 3 Jul 2025
- Results posted
- No
- 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 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INJECTABL-II: Dose Finding, Efficacy and Immunological Response of a Novel Immuno-Adjuvant (IP-001) Following Microwave Ablation or Irreversible Electroporation for Colorectal Liver Metastases.
- ClinicalTrials.gov ID
- NCT06630624
- Acronym / sponsor ID
- INJECTABL-II / 2024.0610
- Keywords
- Colorectal liver metastases, Colorectal hepatic metastases, irreversible electroporation, Microwave ablation, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- M.R. MeijerinkUniversity, hospital or other
- Collaborators
- Immunophotonics, Inc., Angiodynamics, Inc.
- Study start
- 10 Jul 2024 (actual)
- Primary completion
- 1 Aug 2029 (estimated)
- Study completion
- 1 Aug 2031 (estimated)
- First posted
- 8 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objectives of this phase I/II, 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 '3+3' 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, two-armed study assesses the efficacy and immunomodulation of IP-001 following two ablative modalities: arm A (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, 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. 1.0% 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 '3+3' 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, two-armed study assessing the efficacy and immunomodulation of intra-tumoral IP-001-injection following three ablative modalities (arm A (MWA) or arm C (IRE)) in patients with 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 (MWA) and arm B (IRE)) will be randomized in phase 2 part 2 of the trial.
Study population: : In phase 1 of the trial, patients with metastatic CRC and at least 2 CRLM (1-3 cm) that have received at least 1 line of systemic therapy 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 MWA and 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 or IRE.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Firstly, a phase 1, dose-escalation study according to a classic '3+3' design will be performed 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 the ablation for curative intent. Phase 2 part 2 will be conducted in parallel to phase 2 part 1 as a randomized, two-armed study assessing the efficacy and immunomodulation of intra-tumoral IP-001-injection following two ablative modalities (arm A (MWA) or arm C (IRE)) in patients with refractory metastatic CRC.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose esclatation of IP-001 | Experimental | Drug: IP-001Intra-tumoral injection of IP-001 following MWA of two pre-defined colorectal liver metastases (CRLM). Patients will receive sequentially higher doses of the IP-001, always divided equally over the two CRLM, regardless of size. Starting dose will be 8 mL and the dose-escalating steps will be 4 mL up to a total of 16 mL per patient. |
| Phase 2 Part 1 MWA + IP-001 | Experimental | Drug: IP-001One to three colorectal liver metastases (CRLM) will be treated with MWA followed by intra-tumoral injection of IP-001. |
| Phase 2 part 2 MWA + IP-001 | Experimental | Drug: IP-001One to four colorectal liver metastases (CRLM) will be treated with MWA followed by intra-tumoral injection of IP-001. |
| Phase 2 part 2 IRE + IP-001 | Experimental | Drug: IP-001One to four colorectal liver metastases (CRLM) will be treated with IRE followed by intra-tumoral injection of IP-001. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Measurable metastatic CRC based on RECIST v1.1;
- The primary tumor has been resected before study inclusion or the patient is asymptomatic with respect to the in situ primary tumor;
- Last imaging ≤ 4 weeks prior to the on-study ablative procedure;
- Age ≥ 18 years;
- Eastern Cooperative Oncology Group (ECOG) performance status of no more than 1;
Key exclusion criteria (23 listed)
- Compromised liver function defined as warning signs of portal hypertension, INR \> 1,5 without use of anticoagulants, bilirubin \> x 1.5 Upper limit of normal range (ULN) ASAT \>5.0 x ULN, ALAT \>5.0 x ULN.
- Compromised kidney function defined as eGFR \<45 ml/min (using the Cockcroft Gault formula);
- Active autoimmune disease requiring disease-modifying therapy at the time of screening or during the study period: i.e. \> 10 mg prednisolone per day or other immunosuppressive therapy (e.g. methotrexate);
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results;
- Known allergic reaction to shellfish, crabs, crustaceans, or any trial components;
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 |
|---|---|---|
| IP-001Intra-tumoral injection of IP-001 following ablation (MWA or IRE). | Drug | Phase 1 Dose esclatation of IP-001, Phase 2 Part 1 MWA + IP-001, Phase 2 part 2 IRE + IP-001, Phase 2 part 2 MWA + IP-001 |
Primary outcome
Maximum Tolerated Dose (MTD) (Phase 1)
Time frame: During the 10-day DLT-monitoring period.
The highest dose of IP-001 that does not cause unacceptable side effects defined as the dose level below the dose level that caused 2 or more Dose Limiting Toxicites (DLTs).
1-Year Distant Progression Free Survival (DPFS) (Phase 2 part 1)
Time frame: 1 year
Overall DPFS is defined as the time from inclusion to the time of disease progression (according to the RECIST 1.1 guideline) or death (events). Death related to other causes is considered a failure event for DPFS.
Disease Control Rate (DCR) (Phase 2 part 2)
Time frame: 16 weeks
DCR is calculated as the percentage of patients experiencing either iSD (Stable Disease), iPR (Partial Response) or iCR (Complete Response) as best response in target lesions at 16 weeks after treatment according to iRECIST.
18 secondary outcomes
Elimination half-life of the study drug IP-001 in the blood (t1/2 ) (Phase 1 and phase 2 part 2)
Time frame: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Overall Survival (OS; per patient analysis) (All phases)
Time frame: Up to 5 years
(Serious) Adverse Events ((S)AEs) (All phases)
Time frame: Up to 5 years
Duration of best overall response (DoR, per patient analysis) (Phase 2 part 2)
Time frame: Up to 3 years
Local Tumor Progression Free Survival (LTPFS, per lesion analysis) (All phases)
Time frame: Up to 5 years
Distant Progression Free Survival (DPFS; per patient analysis) (All phases)
Time frame: Up to 5 years
Hepatic progression free survival (HPFS; per patient analysis) (All phases)
Time frame: Up to 5 years
Time to progression (TTP; per patient analysis) (All phases)
Time frame: Up to 5 years
Progression-free survival (PFS; per patient analysis) (All phases)
Time frame: Up to 5 years
Disease-free survival (DFS; per patient analysis) (All phases)
Time frame: Up to 5 years
Pain assessment (Per procedure analysis)
Time frame: Up to 1 year
Ablative Success (All phases)
Time frame: Directly after treatment
Quality of Life using EORCT QLQ-C30 questionnaireS (QoL; per patient analysis) (Phase 2)
Time frame: 1 year
Quality of Life using EQ-5D questionnaires (QoL; per patient analysis) (Phase 2)
Time frame: 1 year
Quality of Life using PRODISQ questionnaires(QoL; per patient analysis) (Phase 2)
Time frame: 1 year
Time of maximum observed concentration of the study drug IP-001 in the blood (Tmax) (Phase 1 and phase 2 part 2)
Time frame: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Maximum observed concentration of the study drug IP-001 in the blood (Cmax) (Phase 1 and phase 2 part 2)
Time frame: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Area under the curve from time 0 to the time of the last measurable concentration of the study drug IP-001 in the blood (AUC 0-t) (Phase 1 and phase 2 part 2)
Time frame: Prior to and +1 hour, +2 hours, +6 hours, +12 hours and + 24 hours after study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Individual participant dataSharing planned: No
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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.
Martijn R. Meijerink, Prof. principal investigator
Amsterdam UMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IP-001 in people with Colorectal Cancer and Liver Metastases, run by M.R. Meijerink at 1 site in Netherlands.
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 23 inclusion and 23 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: looking for participants now, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Danielle J. Vos, MD (0204444571 ext. +31, interventieradiologie@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (Phase 1) (time frame: During the 10-day DLT-monitoring period.). The study lists 3 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 3 Jul 2025.