Trial Title:
A Study to Investigate Ompenaclid Combined With FOLFIRI Plus Bevacizumab in Advanced/Metastatic Colorectal Cancer
NCT ID:
NCT05983367
Condition:
Colorectal Cancer
Metastatic Colon Cancer
Conditions: Official terms:
Colorectal Neoplasms
Colonic Neoplasms
Bevacizumab
Conditions: Keywords:
Metastatic colon cancer
KRAS colon cancer
CRC advance cancer
malignant colorectal tumor
RAS mutant colon cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
randomized 1:1
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Ompenaclid
Description:
Ompenaclid (RGX-202-01)
Arm group label:
Ompenaclid + FOLFIRI + Bevacizumab
Other name:
RGX-202-01
Intervention type:
Drug
Intervention name:
Placebo
Description:
Placebo
Arm group label:
Placebo + FOLFIRI + Bevacizumab
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Bevacizumab
Arm group label:
Ompenaclid + FOLFIRI + Bevacizumab
Arm group label:
Placebo + FOLFIRI + Bevacizumab
Intervention type:
Drug
Intervention name:
FOLFIRI regimen
Description:
FOLFIRI regimen (irinotecan 180 mg/m2 over 90 minutes concurrently with folinic acid 400
mg/m2 over 2 hours, and then 5-FU 2400 mg/m2 over 46 hours on Days 1 and 15 of each
28-day cycle)
Arm group label:
Ompenaclid + FOLFIRI + Bevacizumab
Arm group label:
Placebo + FOLFIRI + Bevacizumab
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. Advanced disease, defined as cancer that is either metastatic or locally advanced
and unresectable and for which additional radiation therapy or other locoregional
therapies are not considered feasible.
2. Progression of disease after receiving only 1 prior regimen considered standard of
care for CRC in the advanced/metastatic setting, and it must have been an
oxaliplatin containing regimen. Patients who have mismatch repair deficiency/ high
microsatellite instability (dMMR/MSI-H) CRC must have also received prior treatment
with pembrolizumab or a Food and Drug Administration (FDA)/European Union
(EU)-approved programmed cell death protein 1 (PD-1)/ programmed death-ligand 1
(PD-L1) inhibitor. Patients may have received prior treatment with bevacizumab or an
European Medicines Agency (EMA) approved biosimilar. Patients who developed
metastatic CRC within 12 months of completion of adjuvant oxaliplatin and 5-FU based
therapy are also eligible.
3. Histologic or cytologic evidence of a malignant colorectal tumor of adenocarcinoma
or poorly differentiated histology that is laboratory-confirmed to be RAS mutant.
Confirmation of RAS mutant status by liquid biopsy is acceptable only if the tumor
sample is not available and the liquid biopsy was performed before initiation of the
patient's prior treatment regimen. Patients who convert to RAS mutant status after
initially having documented wild-type histology are not eligible.
4. Disease that is measurable by standard imaging techniques by Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1. For patients with prior radiation
therapy, measurable lesions must be outside of any prior radiation field(s), unless
disease progression has been documented at that disease site subsequent to
radiation.
5. At least 18 years old.
6. ECOG performance score ≤ 1.
7. Adequate baseline organ function, as demonstrated by the following:
1. Calculated creatinine clearance > 60 mL/min per institutional standard.
2. Serum albumin ≥ 2.5 g/dL.
3. Bilirubin ≤ 1.5 x institutional upper limit of normal range (ULN).
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
institutional ULN; patients with hepatic metastases may have AST and ALT ≤ 5 x
institutional ULN.
5. Absolute neutrophil count (ANC) ≥1.5x109/L.
6. Hemoglobin ≥ 8 g/dL and no red blood cell (RBC) transfusions during the prior
14 days.
7. Platelet count ≥ 100 x 109/L and no platelet transfusions during the prior 14
days.
8. If not taking warfarin (or similar vitamin K inhibitor) the following values are
required: international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5
x ULN and either partial thromboplastin time or activated partial thromboplastin
time (PTT or aPTT) ≤ 1.5 x ULN. Patients on warfarin (or similar vitamin K
inhibitor) may be included if on a stable dose with a therapeutic INR < 3.5.
9. Left ventricular ejection fraction (LVEF) x 45% as determined by either
echocardiography (ECHO) or multigated acquisition (MUGA) scanning.
10. Woman of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test within 2 weeks prior to treatment.
11. Men and WOCBP must agree to use acceptable contraceptive methods for the duration of
time on the study and continue to use acceptable contraceptive methods for at least
6 months from the last dose of bevacizumab or 2 months after the last dose of
ompenaclid, whichever is longer.
12. Provides signed informed consent prior to initiation of any study-specific
procedures or treatment.
13. Able to adhere to the study visit schedule and other protocol requirements,
including follow-up for survival assessment
Exclusion Criteria:
1. 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.
2. CRC with histology (or component of histology) consistent with small cell,
neuroendocrine, or squamous carcinoma, or lymphoma.
3. 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).
4. 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.
5. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Imelda Ziekenhuis
Address:
City:
Bonheiden
Zip:
2820
Country:
Belgium
Facility:
Name:
Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
Address:
City:
Woluwe-Saint-Lambert
Zip:
1200
Country:
Belgium
Facility:
Name:
Institut Jules Bordet
Address:
City:
Anderlecht
Country:
Belgium
Facility:
Name:
Antwerp University Hospital
Address:
City:
Antwerp
Zip:
2650
Country:
Belgium
Facility:
Name:
UZ Brussel
Address:
City:
Brussels
Zip:
1090
Country:
Belgium
Facility:
Name:
Grand Hoptial De Charleroi
Address:
City:
Charleroi
Zip:
6000
Country:
Belgium
Facility:
Name:
UZ Leuven
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Facility:
Name:
CHU de Liège University hospital in Liège
Address:
City:
Liege
Zip:
4000
Country:
Belgium
Facility:
Name:
CHU Nantes -hopital hotel Dieu
Address:
City:
Nantes
Zip:
44093
Country:
France
Facility:
Name:
CHU Hôpital Jean Minjoz
Address:
City:
Besançon
Zip:
25000
Country:
France
Facility:
Name:
Centre Georges-François Leclerc
Address:
City:
Dijon
Zip:
21000
Country:
France
Facility:
Name:
Institut Paoli-Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Facility:
Name:
Groupe Hospitalier Paris Saint Joseph - Oncologie
Address:
City:
Paris
Zip:
75074
Country:
France
Facility:
Name:
Hopital Prive des Cotes d'Armor
Address:
City:
Plérin
Zip:
22190
Country:
France
Facility:
Name:
Institut de Cancerologie de l'Ouest
Address:
City:
Saint Herblain Cedex
Zip:
44805
Country:
France
Facility:
Name:
Institut Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Facility:
Name:
Hospital Universitario Marqués de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Facility:
Name:
Hospital de la Santa Creu i Sant Pau
Address:
City:
Barcelona
Zip:
08025
Country:
Spain
Facility:
Name:
Hospital del Mar
Address:
City:
Barcelona
Zip:
08003
Country:
Spain
Facility:
Name:
Hospital Universitari Vall D Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Hospital Universitario Reina Sofía
Address:
City:
Córdoba
Zip:
14004
Country:
Spain
Facility:
Name:
Hospital Universitario Ramón y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Facility:
Name:
Hospital Puerta de Hierro Majadahonda
Address:
City:
Madrid
Zip:
28222
Country:
Spain
Facility:
Name:
Hospital Puerta de Hierro Majadahonda
Address:
City:
Majadahonda
Zip:
28220
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de Valme
Address:
City:
Sevilla
Zip:
41014
Country:
Spain
Facility:
Name:
Hospital Clinico De Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Facility:
Name:
Hospital Clinico Universitario De Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Start date:
October 10, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Inspirna, Inc.
Agency class:
Industry
Source:
Inspirna, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05983367
