Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05983367




Registration number
NCT05983367
Ethics application status
Date submitted
1/08/2023
Date registered
9/08/2023
Date last updated
4/11/2024

Titles & IDs
Public title
A Study to Investigate Ompenaclid Combined With FOLFIRI Plus Bevacizumab in Advanced/Metastatic Colorectal Cancer
Scientific title
A Randomized Phase 2 Study of Ompenaclid Versus Placebo in Combination With FOLFIRI Plus Bevacizumab in Patients With Previously Treated RAS Mutant Advanced or Metastatic Colorectal Cancer
Secondary ID [1] 0 0
RGX-202-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Metastatic Colon Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ompenaclid (RGX-202)
Treatment: Drugs - Placebo
Treatment: Drugs - Bevacizumab
Treatment: Drugs - FOLFIRI regimen

Experimental: RGX-202-01 + FOLFIRI + 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.

Placebo comparator: Placebo + + FOLFIRI + 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.


Treatment: Drugs: Ompenaclid (RGX-202)
RGX-202

Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: Bevacizumab
Bevacizumab

Treatment: Drugs: FOLFIRI regimen
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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate
Timepoint [1] 0 0
36 months
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Duration of Response
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Disease Control Rate
Timepoint [3] 0 0
36 months

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
70
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Belgium
State/province [2] 0 0
Brussels Capital Region
Country [3] 0 0
Belgium
State/province [3] 0 0
Anderlecht
Country [4] 0 0
Belgium
State/province [4] 0 0
Antwerp
Country [5] 0 0
Belgium
State/province [5] 0 0
Brussels
Country [6] 0 0
Belgium
State/province [6] 0 0
Charleroi
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Belgium
State/province [8] 0 0
Liege
Country [9] 0 0
France
State/province [9] 0 0
Loire-Atlantique
Country [10] 0 0
France
State/province [10] 0 0
Besançon
Country [11] 0 0
France
State/province [11] 0 0
Dijon
Country [12] 0 0
France
State/province [12] 0 0
Marseille
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Plérin
Country [15] 0 0
France
State/province [15] 0 0
Saint Herblain Cedex
Country [16] 0 0
France
State/province [16] 0 0
Villejuif
Country [17] 0 0
Spain
State/province [17] 0 0
Cantabria
Country [18] 0 0
Spain
State/province [18] 0 0
Cataluna
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Córdoba
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Majadahonda
Country [23] 0 0
Spain
State/province [23] 0 0
Sevilla
Country [24] 0 0
Spain
State/province [24] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Inspirna, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05983367
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Osamu Takahashi, MD
Address 0 0
Inspirna, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Stephanie Hansen
Address 0 0
Country 0 0
Phone 0 0
(646) 856-9261
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05983367