PERIOP-06: A Study of QBECO Versus Placebo in the Treatment of Colorectal Cancer That Has Spread to the Liver

Sponsor

Sunnybrook Health Sciences Centre (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05677113

Collaborator

(none)

115

Enrollment

Arms

83.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Liver Metastases	Drug: QBECO Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

115 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Feb 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QBECO 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 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.
Placebo Comparator: Placebo A placebo is a liquid that looks like the study drug, but contains no medication.	Drug: Placebo 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.

Arm

Intervention/Treatment

Experimental: QBECO

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

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.

Placebo Comparator: Placebo

A placebo is a liquid that looks like the study drug, but contains no medication.

Drug: Placebo

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.

Outcome Measures

Primary Outcome Measures

The primary outcome will be the 2-year Progression-Free Survival (PFS) rate [2 years]
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.

Secondary Outcome Measures

Clearance of ctDNA. [5 years]
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.
Side-effect profile of QBECO [through study completion, an average of 5 years]
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.
Quality of recovery [Baseline; postoperative day 3, and 6 weeks postoperatively]
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.
Five-year overall survival [5 years]
This will be measured from date of enrollment to the date of death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

Investigators

Principal Investigator: Paul Karanicolas, Paul.Karanicolas@sunnybrook.ca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

The Multiple Organ Dysfunction Syndrome.

Publications

Responsible Party:

Sunnybrook Health Sciences Centre

ClinicalTrials.gov Identifier:

NCT05677113

Other Study ID Numbers:

4023

First Posted:

Jan 10, 2023

Last Update Posted:

Jan 10, 2023

Last Verified:

Jan 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Colorectal Neoplasms

Study Results

No Results Posted as of Jan 10, 2023