Evaluating a new immuno-adjuvant for colorectal liver metastases after ablation treatments

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.

This study is testing a new treatment called IP-001 to see if it can boost the immune response and help people with colorectal liver metastases feel better after they have undergone ablation therapies.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Amsterdam UMC, location VUmc (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Amsterdam, North Holland)
• Trial ID: NCT06630624 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine the optimal dose and assess the efficacy, safety, and immunological response of a novel immuno-adjuvant, IP-001, following various ablative therapies for colorectal liver metastases (CRLM). The study is divided into two phases: Phase 1 focuses on dose escalation to identify a safe level of IP-001 after microwave ablation, while Phase 2 evaluates the efficacy of IP-001 in combination with different ablative techniques, including radiofrequency ablation, microwave ablation, and irreversible electroporation. The trial seeks to enhance the immune response against tumor antigens released during ablation, potentially improving patient outcomes. The primary conducting center for this trial is Amsterdam UMC in the Netherlands.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with measurable metastatic colorectal cancer who have undergone resection of the primary tumor or are asymptomatic.

Not a fit: Patients with compromised liver or kidney function may not benefit from this study due to the exclusion criteria.

Why it matters

Potential benefit: If successful, this study could lead to improved survival rates and better immune responses in patients with colorectal liver metastases.

How similar studies have performed: Other studies exploring the combination of immunotherapy with ablative techniques have shown promise, suggesting potential success for this approach.

Eligibility criteria

All phases:

Inclusion Criteria:

* 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;
* 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.

Exclusion Criteria:

* 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;
* 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

Inclusion Criteria:

* 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;

Exclusion Criteria:

\- No additional exclusion criteria.

Phase 2 part 1:

Inclusion Criteria:

* 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;

Exclusion Criteria:

* 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:

Inclusion Criteria:

* 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.;

Exclusion Criteria:

* 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;

Where this trial is running

Amsterdam, North Holland

• Amsterdam UMC - location VUmc — Amsterdam, North Holland, Netherlands (Recruiting)

Study contacts

• Principal investigator: Martijn R. Meijerink, Prof. — Amsterdam UMC
• Study coordinator: Danielle J. Vos, MD

Conditions Colorectal Cancer; Liver Metastases; Liver Metastasis Colon Cancer; Colorectal liver metastases; Colorectal hepatic metastases; irreversible electroporation; Microwave ablation; Immunotherapy