Dose Finding, Efficacy and Immunological Response of IP-001 Following MWA or IRE for CRLM

NCT06630624 | Recruiting Phase 1 DMC

• 2 other identifiers: 2024.06102023-504572-25-00
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Colorectal Cancer; Liver Metastases; Liver Metastasis Colon Cancer

Keywords

Colorectal liver metastases; Colorectal hepatic metastases; irreversible electroporation; Microwave ablation; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• 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).

  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.

  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.

  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)

  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)

  Up to 5 years

• (Serious) Adverse Events ((S)AEs) (All phases)

  Up to 5 years

• Duration of best overall response (DoR, per patient analysis) (Phase 2 part 2)

  Up to 3 years

• Local Tumor Progression Free Survival (LTPFS, per lesion analysis) (All phases)

  Up to 5 years

Other Outcomes (3)

• Immunomodulation in tissue biopsies (Phase 1 and phase 2 part 2)

  Prior to the procedure and 4 weeks post-procedure.

• Immunomodulation in circulating immunecells (Phase 1 and phase 2 part 2)

  prior to the study procedure and +1 day, +10 days, +4 weeks and +8 weeks after the study procedure

• Effect on circulating tumor DNA (ctDNA) (Phase 2 part 1)

  1 year

Study Arms (4)

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.

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.

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.

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.

Drug: IP-001

Interventions

IP-001 DRUG

Intra-tumoral injection of IP-001 following ablation (MWA or IRE).

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic CRC based on RECIST v1.1;
• 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;
• Written informed consent.

You may not qualify if:

• 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;
• Phase 1
• 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;

Sponsors & Collaborators

• M.R. Meijerink: lead
• Immunophotonics, Inc.: collaborator
• Angiodynamics, Inc.: collaborator

Study Sites (1)

Amsterdam UMC - location VUmc

Amsterdam, North Holland, 1118 HV, Netherlands

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

N-dihydrogalactochitosan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Martijn R. Meijerink, Prof.

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle J. Vos, MD

CONTACT

0204444571; interventieradiologie@amsterdamumc.nl

Martijn R. Meijernk, Prof.

CONTACT

020-4444571; interventieradiologie@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. dr.

Model Details: 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.

Study Record Dates

• First Submitted: September 6, 2024
• First Posted: October 8, 2024
• Study Start: July 10, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2031
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)