A Study to Investigate Ompenaclid Combined With FOLFIRI Plus Bevacizumab in Advanced/Metastatic Colorectal Cancer
- Conditions
- Colorectal CancerMetastatic Colon Cancer
- Interventions
- Registration Number
- NCT05983367
- Lead Sponsor
- Inspirna, Inc.
- Brief Summary
The purpose of this study is to measure tumor response to treatment with ompenaclid (RGX-202-01) in patients with previously treated RAS mutant advanced or metastatic CRC. All patients will receive treatment with FOLFIRI and bevacizumab. In addition, patients will be randomized to receive either ompenaclid 3000 mg BID or matching placebo (herein referred to as Study Drug). Each treatment cycle is 28 days in duration.
- Detailed Description
This is a Phase 2, randomized, double-blind placebo-controlled study of ompenaclid or matching placebo (Study Drug) in combination with standard-of-care FOLFIRI plus bevacizumab as background therapy in patients with previously treated RAS mutant advanced or metastatic CRC. Randomization will be stratified by whether or not the patient received prior treatment with bevacizumab or an EMA-approved biosimilar. Written informed consent must be obtained prior to initiating any screening activities, except where patients have agreed to the use of previously available tests completed within 28 days of the planned first dose of Study Drug, e.g., computed tomography (CT)/magnetic resonance imaging (MRI) scans. Screening for study eligibility must be completed within 28 days prior to first dose of Study Drug. Patients who are determined to be eligible, based on Screening assessments, will be randomized in the study, and receive their first dose of Study Drug on Cycle 1, Day 1. A treatment cycle is 28 days in duration. Patients will be randomized in a 1:1 ratio to receive oral administration of the five 600-mg tablets BID of ompenaclid or matching placebo (Study Drug). The intravenous FOLFIRI dose and schedule for all patients will be irinotecan 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours,followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. The bevacizumab dose of 5 mg/kg will be administered intravenously on Days 1 and 15 of each 28-day cycle. During treatment, patients will attend study center visits and have study evaluations performed as detailed in the Schedule of Events (Table 1-1). All routine study visits are to be conducted on an outpatient basis. Patients may continue to receive Study Drug until the development of PD, or another discontinuation criterion is met, including unacceptable toxicity, voluntary withdrawal from treatment, or closure of the study by the Sponsor; no maximum duration of therapy has been set. After discontinuation of the Study Drug, patients will complete an End of Treatment (EOT) visit within 21 days after their last dose of Study Drug. Safety follow-up is to be conducted by telephone 30 days (+/- 3 days) after their last dose of Study Drug and longer if drug-related AEs have not resolved at that time. Patients and/or their health care providers will also be contacted by telephone approximately every 90 days for information on evidence of PD in settings in which discontinuation of Study Drug was for reasons other than PD, such as an adverse event (AE) or investigator discretion, and/or for assessment of survival status (tumor measurements as specified in the protocol are not required after the EOT visit). This extended follow-up for disease status and survival after discontinuation of the Study Drug may continue until the target number of disease progression events have been observed or for 12 months after the patient's EOT visit, whichever is later. The End of Study for a given patient is defined as the date of the last extended follow-up disease/survival status, or until death, withdrawal of consent, loss to follow-up, or study closure, whichever occurs first.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 70
Not provided
- Persistent clinically significant toxicities (Grade ≥ 2) from previous anticancer therapy. Excluded are Grade 2 chemotherapy-related neuropathy and alopecia which are permitted and Grade 2 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, or can be managed with available medical therapies.
- CRC with histology (or component of histology) consistent with small cell, neuroendocrine, or squamous carcinoma, or lymphoma.
- Received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 14 days prior to study therapy administration (42 days for prior nitrosourea or mitomycin-C).
- Received treatment with an investigational systemic anticancer agent within 5 half lives of the investigational systemic therapy or within 28 days, whichever is shorter prior to Study Drug administration.
- Has an additional active malignancy that may confound the assessment of the study endpoints. Patients with a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer with no evidence of progressive disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ompenaclid + FOLFIRI + Bevacizumab Ompenaclid Ompenaclid (RGX-202-01) 3000mg PO (tablets) BID; Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle. Ompenaclid + FOLFIRI + Bevacizumab Bevacizumab Ompenaclid (RGX-202-01) 3000mg PO (tablets) BID; Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle. Ompenaclid + FOLFIRI + Bevacizumab FOLFIRI regimen Ompenaclid (RGX-202-01) 3000mg PO (tablets) BID; Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle. Placebo + FOLFIRI + Bevacizumab Placebo Placebo (tablets) PO + Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle. Placebo + FOLFIRI + Bevacizumab Bevacizumab Placebo (tablets) PO + Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle. Placebo + FOLFIRI + Bevacizumab FOLFIRI regimen Placebo (tablets) PO + Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Overall Response Rate From randomization until development of radiographic disease progression (estimated up to 24 months). ORR is defined as the proportion of patients achieving a best overall response (BOR) of complete response (CR) or partial response (PR) per the investigators using RECIST version 1.1.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) From randomization until development of radiographic disease progression or death due to any cause, whichever comes first (estimated up to 24 months). PFS is defined as the time from the date of randomization to the date of objectively determined progressive disease (PD) per the investigators using RECIST version 1.1 or death from any cause, whichever occurs first.
Overall Survival (OS) From randomization until death due to any cause (estimated up to 36 months). OS is defined as the time from the date of randomization to the date of death from any cause.
Duration of Response (DoR) From randomization until development of radiographic disease progression or death due to any cause, whichever comes first (estimated up to 24 months). DoR is defined as the time from the date of objectively determined PR or CR (whichever status is recorded first) to the date of PD per the investigators using RECIST version 1.1 or death from any cause, whichever occurs first.
Disease Control Rate (DCR) From randomization until development of radiographic disease progression (estimated up to 24 months). DCR is defined as the proportion of patients achieving a BOR of CR, PR, or stable disease (SD).
Frequency of Adverse Events (AEs) From the signing of informed consent until 30 days (+/- 3 days) after the last dose of study drug. (estimated up to 24 months). Percentage of patients with treatment-emergent AEs (TEAE).
Pharmacokinetics of ompenaclid At Cycle 1 day 15 and Cycle 2 day 15 (each cycle is 28 days in length). Steady state concentration
Exploratory biomarkers that may correlate with efficacy outcomes At baseline CKB levels identified in baseline tumor samples
Trial Locations
- Locations (27)
Imelda Ziekenhuis
🇧🇪Bonheiden, Antwerpen, Belgium
Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
🇧🇪Woluwe-Saint-Lambert, Brussels Capital Region, Belgium
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
Antwerp University Hospital
🇧🇪Antwerp, Belgium
UZ Brussel
🇧🇪Brussels, Belgium
Grand Hoptial De Charleroi
🇧🇪Charleroi, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHU de Liège University hospital in Liège
🇧🇪Liege, Belgium
CHU Nantes -hopital hotel Dieu
🇫🇷Nantes, Loire-Atlantique, France
CHU Hôpital Jean Minjoz
🇫🇷Besançon, France
Centre Georges-François Leclerc
🇫🇷Dijon, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Groupe Hospitalier Paris Saint Joseph - Oncologie
🇫🇷Paris, France
Hopital Prive des Cotes d'Armor
🇫🇷Plérin, France
Institut de Cancerologie de l'Ouest
🇫🇷Saint Herblain Cedex, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Cataluna, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitari Vall D Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Hospital Universitario Virgen de Valme
🇪🇸Sevilla, Spain
Hospital Clinico De Valencia
🇪🇸Valencia, Spain
Hospital Clinico Universitario De Valencia
🇪🇸Valencia, Spain