A Study of QBECO Versus Placebo in the Treatment of Colorectal Cancer That Has Spread to the Liver

Study Overview
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Brief Summary
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The goal of this type of clinical trial is t to answer the following question: Can the chance of colorectal cancer progressing be lowered by taking a medication, QBECO, before and after surgery? The goal of this study is to find out if this approach is better or worse than the standard of care for your type of cancer. The standard of care is defined as care most people get for metastatic colorectal cancer. There is currently no standard of care drug being given before or after surgery to prevent further spread of your cancer. Participants will be asked to self-inject the study medication before surgery for minimum of 11 days and after surgery for minimum of 41 days. Participants will be followed up every 3 months for 2 years, with a final visit at year 5.

Detailed Description
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PERIOP-06 is a multicenter, phase II, blinded, randomized, placebo-controlled trial in adult patients planned to undergo resection of colorectal liver metastases (CRLM) for complete clearance of all visible disease. The investigational product for the study is QBECO. QBECO is a site specific immunomodulator (SSI) designed to promote innate immune responses in the gastrointestinal tract and related organs, including the liver. This trial is motivated by the promising preclinical and clinical data supporting the safety and efficacy of QBECO in attenuating postoperative immunosuppression and the resulting proliferation of cancer. The primary objective of this randomized controlled trial is to determine if QBECO administered perioperatively can improve 2-year Progression-Free Survival in adult patients undergoing resection of CRLMs for complete clearance of metastatic disease. The main secondary objectives will be to: Determine the effect of QBECO on the frequency and kinetics of clearance (and recurrence) of circulating tumor DNA (ctDNA) in the postoperative period and further evaluate the use ctDNA as part of ongoing surveillance. Determine the side-effect profile of perioperative QBECO. Determine the effect of QBECO on 5-year overall survival Approximately 115 participants will be randomized to receive a placebo or the investigational product, QBECO. QBECO or placebo will be administered according to the following regimen: 0.1mL subcutaneous injections every two days for 11-120 days preoperatively, and 41 days postoperatively. Participants will be followed for 5 years after surgery.

Official Title
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A Phase II Study of Perioperative QBECO Site Specific Immunomodulator (Qu Biologics®) in Patients With Metastatic Colorectal Adenocarcinoma Within the Liver Undergoing Resection

Conditions
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Colorectal Cancer, Liver Metastases

Intervention / Treatment
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* Drug: QBECO
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 years or older at time of enrollment. Pathologic diagnosis of colorectal carcinoma with clinical diagnosis of liver metastases Planned to undergo resection of liver lesions for complete clearance of all visible metastatic disease. This will include those who may undergo synchronous resection of the primary colorectal cancer and/or those who may receive a combination of surgery and ablation to treat all lesions. Computerized Tomography (CT) of the chest, abdomen, and pelvis with intravenous (IV) contrast within 6 weeks prior to enrollment. MRI of the liver within 6 weeks prior to enrollment OR within 6 weeks prior to starting neoadjuvant chemotherapy (for patients treated with chemotherapy). Planned to receive the last dose of neoadjuvant chemotherapy at least 25 days prior to surgery (for patients treated with neoadjuvant chemotherapy). Agree to comply with the contraceptive requirements of the protocol when applicable Willing and able to either perform subcutaneous injections according to the study protocol, or receive the injections from a caregiver delegated by the participant. Able to provide informed consent or has a substitute decision maker capable of providing consent on their behalf. Exclusion Criteria: Prior or current evidence of extrahepatic metastases. Patients with small (<1.0 cm) indeterminate pulmonary nodules may be included at the investigator's discretion. Prior hepatic arterial infusion or embolization. Prior portal vein embolization, ablation, or liver resection are permitted. Patients with any invasive cancer history other than colorectal cancer in the last 5 years. In situ disease (e.g., melanoma in situ, ductal carcinoma in situ of the breast) or non melanoma skin cancers are permitted. Patients with a documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents. This includes patient requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent, or depot corticosteroids in the 6 weeks before enrollment) or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporine, etc.) within the 14 days prior to enrollment or a reasonable expectation that the patient may require such treatment during the course of the study. Inhaled or topical or inter-articular steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Steroids used for premedication prior to chemotherapy or as part of a chemotherapy regimen are allowed. Patients with known active human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infections. Pregnant patients or those who are nursing an infant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QBECO<br>QBECO is an SSI formulated from inactivated E. coli bacteria that is specifically designed to target pathologies of the gastrointestinal (GI) tract and related organs, such as the liver. This trial will test the hypothesis that in patients undergoing resection of colorectal liver metastases (CRLMs), perioperative treatment with QBECO will attenuate the postoperative immune suppression and will improve progression-free survival (PFS). | Drug: QBECO<br>* QBECO is a site specific immunomodulator (SSI) designed to promote innate immune responses in the gastrointestinal tract and related organs, including the liver. QBECO will be administered according to the following regimen: 0.1mL self-administered subcutaneous injections every 2 days for 11-120 days preoperatively, and 41 days postoperatively.<br>|
| Placebo Comparator: Placebo<br>A placebo is a liquid that looks like the study drug, but contains no medication. | Drug: Placebo<br>* Placebo will be prepared in the same way as the IP. Placebo will be administered according to the following regimen: 0.1mL self-administered subcutaneous injections every 2 days for 11-120 days preoperatively, and 41 days postoperatively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be the 2-year Progression-Free Survival (PFS) rate | PFS will be defined as the time from enrollment to the first event that is either locoregional recurrence (of the resected primary colorectal adenocarcinoma or the resected ± intraoperatively ablated metastatic disease), distant metastases, or death from any cause. Section 5 further defines PFS and its measurement. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of ctDNA. | A substantial body of research has demonstrated associations between ctDNA and cancer progression.Timing of measurement will be at baseline (which will occur within 14 days prior to the first dose of Investigational Product (IP) and at least 14 days after the last dose of chemotherapy, when applicable), preoperatively on the day of surgery, and postoperatively. A sample of fresh tumour tissue will be obtained from each resected hepatic and extrahepatic (when applicable) tumour site, resection of the primary colorectal carcinoma, along with a sample of normal adjacent tissue (one per surgical specimen) to tailor the ctDNA assay to the individual participant's tumour profile. If tumour tissue is not available from the resected specimen, tumour tissue from a prior resection or biopsy of the participant's adenocarcinoma may be requested. If disease progression is detected, ctDNA will also be measured at that time. | 5 years | 
| Side-effect profile of QBECO | This will include an evaluation of AEs and postoperative complications in the treatment and control groups. A postoperative complication will be defined as any deviation from the normal postoperative course. All clearly related signs, symptoms, and abnormal diagnostic procedures should be recorded in the source document and should be grouped under one diagnosis. The deviation must be possibly or probably related to the surgery and must occur postoperatively. The modified Clavien-Dindo system will be used to define and classify postoperative complications. | through study completion, an average of 5 years | 
| Quality of recovery | Measured by the QoR-40. The QoR-40 is a validated tool designed to measure the early postoperative health status of patients. The tool has been widely used as a patient-reported outcome measure of recovery after surgery and has been translated into multiple languages. Timing of measurement will be at baseline (which will occur within 14 days prior to the first IP dose and at least 14 days after the last dose of chemotherapy, when applicable), on postoperative day (POD) 3, and 6 weeks postoperatively. The survey may be administered in person or virtually by telephone or video call. | Baseline; postoperative day 3, and 6 weeks postoperatively | 
| Five-year overall survival | This will be measured from date of enrollment to the date of death. | 5 years |