The goal of this clinical trial is to learn if a new injectable drug (IP-001), administered after standard liver tumor ablation, can help prevent cancer from returning in people (males/females, ≥18 years old) with colorectal cancer that has spread only to the liver. The study will determine if injecting IP-001 into a liver tumor(s) after ablation will reduce the risk of cancer coming back in the liver and from spreading elsewhere in the body, will stimulate the immune system, will have any side effects, and will help improve a patient's response to other cancer therapies. Researchers will compare a standard of care liver ablation alone (microwave ablation \[MWA\], a technique that destroys tumors using heat), with MWA plus a high-dose IP-001 or MWA with a low-dose IP-001. During the treatment procedures, the doctor first performs the standard microwave ablation to destroy the tumor. Then, in the experimental-drug arms, IP-001 is injected in and around the treated tumor area to activate the immune system locally so that the body is more likely to find and eliminate any remaining cancer cells.
This is a Phase 2/3, three-arm, dose finding, randomized, controlled, patient-blinded, international, adaptive design study in patients with liver-only metastatic colorectal cancer. The purpose is to investigate the efficacy and safety of the two different dose concentrations of IP-001 for Injection administered intratumorally following standard of care (SOC) complete thermal ablation of liver tumors with microwave ablation (MWA) compared SOC MWA alone. MWA alone is selected as the control because, in patients with liver-only metastatic colorectal cancer treated with curative intent, MWA is an accepted SOC therapeutic strategy and routine continuation of systemic therapy in this context is not mandated by guidelines and remains heterogeneous across institutions. The study is designed with a seamless transition from Phase 2 to the Phase 3 based on prespecified dose selection and interim efficacy and safety criteria. Phase 2 will include three-arms: MWA alone, MWA plus 10 mg/ml IP-001, or MWA plus 1 mg/ml IP-001. Crossover from the Control Arm to an Experimental Arm is not allowed. Phase 3 will continue to be randomized between the MWA alone (control) and the MWA plus IP-001 dose selected based on the Phase 2 interim (futility) analysis. The trial will consist of the following three periods described below. 1. Screening Period: Up to 28 days for screening assessments to determine study eligibility. 2. Treatment and Follow-up Period: On Treatment Day 1, in a single session, all patients will undergo SOC hepatic tumor MWA with predetermined margins. Immediately following ablation, patients in the Experimental Arms will receive the appropriate dose of IP-001 intratumorally into all ablated tumor(s). Blood samples will be taken before treatment starts, and then again on various days after treatment to help check for important blood markers in and how the drug works in the body. In addition, patients will undergo post-treatment efficacy and safety and tolerability efficacy assessments for 12 weeks before patients move on to standard surveillance monitoring. 3. Surveillance Period: Patients will be followed for efficacy, concomitant medication and procedures, and survival, every 3 months for the first year, and then every 6 months thereafter for 5 years after the initial treatment. Patients who develop a new or recurrent tumor(s) may be eligible receive additional treatment, as appropriate, including study retreatment, other standard liver treatments, or systemic anti-cancer therapy. Patients will be followed for subsequent anticancer therapies/procedures, progression, and survival status, as indicated, for 5 years after the original treatment day to help researchers determine if IP-001 will improve a patient's response to other cancer therapies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
717
IP-001 is a novel, non-cytotoxic, immunostimulatory glycan polymer administered as a single intratumoral injection into the ablation zone immediately following standard of care image-guided microwave thermal ablation of a target tumor lesion.
IP-001 is a novel, non-cytotoxic, immunostimulatory glycan polymer administered as a single intratumoral injection into the ablation zone immediately following standard of care image-guided microwave thermal ablation of a target tumor lesion.
Microwave ablation is a common medical procedure where doctors use imaging (like ultrasound or CT) to guide a thin probe into a tumor. The probe gives off microwave energy that heats up the tumor from the inside, causing the cancer cells in that spot to die. Unlike treatments such as chemotherapy or immunotherapy, which travel through the whole body, microwave ablation works only on the specific area being treated. It does not involve any drugs or medicines circulating in the bloodstream. It is a local treatment that targets just the tumor.
To compare the efficacy of IP-001 following standard-of-care (SOC) complete hepatic tumor ablation vs SOC complete hepatic tumor ablation alone in prolonging progression-free survival
Progression-free survival (PFS) is defined as the time from randomization to first occurrence of objectively documented (1) extrahepatic progression or (2) intrahepatic progression (that could not be treated with curative-intent locoregional therapy) per RECIST v1.1, assessed by a Blinded Independent Central Review (BICR), or (3) death from any cause, whichever occurs first.
Time frame: From date of randomization to first documented progression (extrahepatic, or intrahepatic that could not be treated with curative-intent locoregional therapy) or death from any cause, whichever comes first, assessed up to 5 years.
To compare disease control of IP-001 following SOC complete hepatic tumor ablation vs SOC complete hepatic tumor ablation alone
* Extrahepatic PFS (ePFS) is defined as the time from randomization to first documented extrahepatic progression per RECIST v1.1 assessed by BICR, or death from any cause, whichever occurs first. * Intrahepatic PFS (iPFS) is defined as the time from randomization to first documented intrahepatic progression per RECIST v1.1 assessed by BICR, or death from any cause, whichever occurs first. * PFS is defined as the time from randomization to first documented (1) extrahepatic progression or (2) intrahepatic progression that could not be treated with curative-intent locoregional therapy per RECIST v1.1, assessed by the Investigator, or (3) death from any cause, whichever occurs first. * ePFS is defined as the time from randomization to first occurrence of objectively documented extrahepatic progression per RECIST v1.1, assessed by the Investigator, or death from any cause, whichever occurs first.
Time frame: From date of randomization to first documented progression (extrahepatic, or intrahepatic that could not be treated with curative-intent locoregional therapy) or death from any cause, whichever comes first, assessed up to 5 years.
To compare survival outcomes of IP-001 following SOC complete hepatic tumor ablation vs SOC complete hepatic tumor ablation alone
Overall survival (OS) is defined as the time from randomization to death from any cause.
Time frame: From date of randomization to first documented progression (extrahepatic, or intrahepatic that could not be treated with curative-intent locoregional therapy) or death from any cause, whichever comes first, assessed up to 5 years.
To compare time to progression events between IP-001 following SOC complete hepatic tumor ablation and SOC complete hepatic tumor ablation alone
* Time to Progression (TTP) is defined as the time from randomization to objectively documented intrahepatic or extrahepatic progression, per RECIST v1.1, assessed by BICR. * TTP is defined as the time from randomization to objectively documented intrahepatic or extrahepatic progression, per RECIST v1.1, assessed by the Investigator. * Time to Loss of Hepatic Control (TLHC) is defined as the time from randomization to objectively documented intrahepatic progression that cannot be treated with curative intent by locoregional therapy, assessed by the Investigator.
Time frame: From date of randomization to first documented progression (extrahepatic or intrahepatic), assessed up to 5 years.
To compare safety and tolerability (via incidence of treatment-emergent adverse events) of IP-001 following SOC complete hepatic tumor ablation and SOC complete hepatic tumor ablation alone.
Incidence and severity of AEs, serious adverse events (SAEs), adverse events of special interest (AESIs), deaths, and laboratory abnormalities.
Time frame: 12 weeks following treatment or resolution (whichever is longer).
To compare the impact on patient-reported disease-specific health-related quality of life (HRQoL) outcomes of treatment with IP-001 following SOC complete hepatic tumor ablation vs SOC complete hepatic tumor ablation alone
Changes in questionnaire dimensions from baseline to 1 year post treatment as determined by scores on the patient-reported outcome (PRO) scale European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC) QLQ-C30 with the Colorectal Liver Metastases Module LMC21 for global health status/HRQoL, physical function, and role function.
Time frame: From baseline (screening) until 1 year after treatment.
To compare the impact on patient-reported general health-related quality of life (HRQoL) outcomes of treatment with IP-001 following SOC complete hepatic tumor ablation vs SOC complete hepatic tumor ablation alone
Changes in questionnaire dimensions from baseline to end of study as determined by scores on the patient-reported outcome (PRO) scale EuroQoL 5 Dimension 5 Level (EQ-5D-5L)
Time frame: From baseline (screening) until patient's last visit, assessed up to 5 years.
To determine the maximum plasma concentration (Cmax) of intratumorally administered IP-001
Cmax will be obtained after administration of IP-001
Time frame: Baseline (screening) through Day 45
To determine the time to reach maximum plasma concentration (Tmax) of intratumorally administered IP-001
Tmax will be obtained after administration of IP-001
Time frame: Baseline (screening) through Day 45
To determine the area under the plasma concentration-time curve (AUC0-t) of intratumorally administered IP-001
AUC0-t will be obtained after administration of IP-001
Time frame: Baseline (screening) through Day 45
To determine the half-life (T1/2) of intratumorally administered IP-001
T1/2 will be obtained after administration of IP-001
Time frame: Baseline (screening) through Day 45
Kelly E Porterfield
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