Solid Tumors (Phase 1)Phase 1AROG4-01-01NCT06652529
Phase 1 Dose Escalation and Expansion to Evaluate AROG4-01 in Patients With Advanced Solid Tumors
A Phase 1 study testing AROG4-01 in people with Solid Tumors (Phase 1) and Mesothelioma, run by Aromics Therapeutics.
Trial summary
The goal of this clinical trial is to learn if drug AROG4-01 is safe in patients with solid tumors who have no available treatment alternative. Different doses will be tested in order to identify the most suitable one. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors (Phase 1), Mesothelioma, Colorectal Carcinoma
- What is being tested?
- AROG4-01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- Jan 2025to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients, 18 years or older, with a diagnosis (histology or citology) of advanced (unresectable or metastatic) solid tumor for which there is no curative therapy, has progressed on SOC treatment or for whom SOC is no longer an option. In part B patients will be included in different cohorts according to the histology (mesothelioma vs. non-mesothelioma).
- Evaluable (part A) or measurable disease (part B) as per RECIST v1.1 (part A) or mRECIST v1.1. (part B). Progressive disease to the on or following the last line of antitumor treatment.
- ECOG performance status ≤ 2.
- Life expectancy ≥12 weeks.
- Hematology and clinical chemistry laboratory parameters within acceptable ranges.
- Adequate organ function as defined below:
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- Hemoglobin ≥9 g/dL
- Neutrophil count ≥1.000x10/mcL
- Platelets ≥100.000/mcL
- Total bilirubin ≤1,5 x Upper Limit of Normal (ULN) (unless Gilbert's Disease)
- AST (SGOT)/ALT (SGPT) ≤ 2,5 x institutional ULN (or ≤ 5X ULN in the presence of liver metastases)
- Creatinine ≤1.5 mg/dL and creatinine CL ≥40 mL/min (calculated using the Cockcroft-Gault formula)
- Adequate coagulation profile as defined below:
- INR≤ 1,5
- aPTT ≤ 1,5 x ULN
- Serum or urine negative pregnancy test for women with childbearing potential.
- No previous antitumor treatment (radiation therapy, systemic treatment, or surgery) in the previous 28 days and current adverse events from them ≤ grade 1.
Who cannot join
- Systemic anti-cancer therapy within 4 weeks prior to study admission.
- Radiation therapy within 4 weeks prior to study entry.
- Any major surgery within 4 weeks before first dose of study treatment No major surgery must be planned during the trial expected treatment. receiving study treatment. Participants with recent surgery with only local anesthesia may be included.
- Non-malignant systemic disease including cerebrovascular accident, myocardial infarction in the last 6 months, unstable angina pectoris, unstable cardiac arrhythmia, New York Heart Association (NYHA) Class III or IV heart failure, coagulation abnormalities and clinically significant pulmonary compromise, .
- Left ventricular ejection fraction below institutional normal limits.
- Patients with symptomatic central nervous system (CNS) primary tumor or metastases (including leptomeningeal carcinomatosis). Patients with documented treated CNS metastases stable for at least 4 weeks may be enrolled at the discretion of the investigator.
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- Breast feeding, pregnancy or not willing to adopt safe contraceptive measures by the patient or the patient's partner, to become pregnant during treatment or within 6 months after the end of treatment.
- Patients with active uncontrolled infection or known to be serologically positive for human immunodeficiency virus (HIV), hepatitis B (except HbsAc after vaccination) or hepatitis C infection.
- Any other diseases or medical condition that may interfere with the planned treatment, compliance, or place the patient at risk if participating in the study, at investigator criteria.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: First in Human Phase 1 Dose Escalation and Expansion Clinical Trial to Evaluate the Safety, Pharmacokinetics and Antitumor Activity of Intravenous AROG4-01 in Patients With Advanced Solid Tumors
The goal of this clinical trial is to learn if drug AROG4-01 is safe in patients with solid tumors who have no available treatment alternative. Different doses will be tested in order to identify the most suitable one. Once it is identiffied, up to 20 patients will be treated with that dose, to check if thye get clinical benefit.
Participants will: receive intravenous administrations of ARG4-01 twice weekly, and visit the clinic twice every week for checkups and tests.
Read the detailed description
This study is an open label, Phase 1 dose escalation trial with two expansion cohorts to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of AROG4-01 in patients with mesothelioma and other advanced solid tumors.
This clinical trial is divided into two parts: dose escalation (part A), and dose expansion (part B).
Dose escalation In the present trial, patients will be enrolled sequentially into escalating dose cohorts, and will continue receiving AROG4-01 until disease progression, unacceptable toxicity, withdrawal of consent or otherwise as specified in the investigational medicinal product (IMP) discontinuation criteria.
Patients in a dose cohort will receive AROG4-01 as intravenous (IV) administrations at the same dose in a dosing interval of twice a week, four weeks (equal to one cycle) consecutively without interruption, except when necessary to manage adverse events (AEs).
Six cohorts at escalating dose levels are envisaged. Dose escalation may continue beyond, until the recommended for part B dose, which will be the recommended for phase 2 dose (RP2D), can be defined based on safety, preliminary efficacy, PK and PD data, based on the recommendations of the Safety Review Committee (SRC). The RP2D is defined as the recommended for phase 2 dose, but two cohorts will be treated as part of the phase 1 expansion with that particular dose, in order to get more safety and efficacy data.
Escalation to the next dose level will occur following the SRC meeting for the most recently completed cohort. In considering the appropriate dose level for the next cohort the following will be applied:
- The maximum dose increment will be limited to 100% if patients of a given cohort experience one Grade ≥ 2 AE during the DLT period or if at least one patient decreases >10% weight.
- The maximum dose increment will be limited to 50% if a patient of a given cohort experiences one DLT during the DLT period.
If the prior circumstances do not occur, dose escalation will continue at higher increments (not exceeding three times prior dose level), as determined by the SRC.
Extension phase At the dose expansion part, two cohorts of patients with advanced solid tumor each will be recruited. One cohort of patients with advanced MPM (cohort 1) and a second cohort of patients with other solid tumors (cohort 2). Patients will be treated with AROG4-01 at the RP2D of AROG4-01 resulting from part A.
- Conditions
- Solid Tumors (Phase 1), Mesothelioma, Colorectal Carcinoma, Ovarian Cancer, NSCLC (Advanced Non-small Cell Lung Cancer)
- Being tested
- AROG4-01
- Keywords
- Phase I, AROG4-01, mesothelioma, solid tumors, NSCLC, ovarian cancer, colorectal cancer, dose escalation
- Medical subject headings
- Mesothelioma, Colorectal Neoplasms, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AROG4-01Drug
Also called Dose level 2, Dose level 3, Dose level 4, Dose level 5
AROG4-01 will be administered as IV infusions in biweekly dosing interval. The first dosing day will be Day 1, 28 days cycle.
AROG4-01Drug
AROG4-01 will be administered as IV infusions in biweekly dosing interval. The first dosing day will be Day 1, 28 days cycle.
This study is an open label, Phase 1 dose escalation trial with two expansion cohorts. The study consists of two parts:
- Part A: Dose escalation in patients with advanced solid tumors. Approximately 8 to 20 patients in total will be enrolled in part A, covering up to 6 dose levels.
- Part B: At the dose expansion phase, AROG4-01 two cohorts of ten patients with advanced solid tumor each will be recruited. One cohort of patients with advanced MPM (cohort 1) and a second cohort of patients with other solid tumors (cohort 2).
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | Four dose levels will be tested. If there are no safety concerns, dose escalation may continue with up to two additional dose levels Receives: Drug: AROG4-01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of AROG4-01
To evaluate the safety and tolerability of AROG4-01 in adult patients with advanced solid tumors, including determination of the main DLT associated to AROG4-01.
To assess the MTD (RP2D) defined as the highest dose at which no more than one in six patients experience a AROG4-01-related DLT. DLTs will be evaluated after the first treatment cycle.
Measured: 12 months
Secondary outcomes (3)
To assess the preliminary antitumor activity of AROG4-01 monotherapy as measured by Overall Response Rate (ORR) according to standard criteria (RECIST 1.1 [18] or mRECIST v1.1
- To assess progression-free survival (PFS) in patients with mesothelioma and other advanced solid tumors.
Measured: 24 months
To characterize the PK of AROG4-01.
Cmax
Measured: 24 months
To characterize the PK of AROG4-01
half-life
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study startJan 2025 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Solid Tumors (Phase 1)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- This clinical trial is divided into two parts: dose escalation (part A), and dose expansion (part B). In part A (dose escalation), patients will be treated with AROG4-01 at different doses, starting at 9 mg/m2. Escalation to next dose levels will occur following the Safety Review Committee meeting for the most recently completed cohort. The MTD decided as per part A (dose escalation) will be used for part B (dose expansion).
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aromics Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06652529
- Sponsor's protocol ID
- AROG4-01-01
- Acronym
- AROG4-01-01
- Status last verified
- Nov 2024
- First submitted
- 17 Oct 2024
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Aubets E, J Felix A, Garavis M, Reyes L, Avino A, Eritja R, Ciudad CJ, Noe V. Detection of a G-Quadruplex as a Regulatory Element in Thymidylate synthase for Gene Silencing Using Polypurine Reverse Hoogsteen Hairpins. Int J Mol Sci. 2020 Jul 16;21(14):5028. doi: 10.3390/ijms21145028.
PubMed 3270871019- Phan, A. T., & Patel, D. J. (2005). "RNA tetraplexes, structures and functions." Biochemistry, 44(2), 639-649. doi:10.1021/bi048804m
Simon, J. S., et al. (2018). "Hairpin structures near G-quadruplexes can modulate G4 stability and drug binding." Nature Communications, 9, 4621. doi:10.1038/s41467-018-07055-8
Rhodes D, Lipps HJ. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res. 2015 Oct 15;43(18):8627-37. doi: 10.1093/nar/gkv862. Epub 2015 Sep 8.
PubMed 26350216
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First in Human Phase 1 Dose Escalation and Expansion Clinical Trial to Evaluate the Safety, Pharmacokinetics and Antitumor Activity of Intravenous AROG4-01 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06652529
- Acronym / sponsor ID
- AROG4-01-01 / AROG4-01-01
- Conditions
- Solid Tumors (Phase 1), Mesothelioma, Colorectal Carcinoma, Ovarian Cancer, NSCLC (Advanced Non-small Cell Lung Cancer)
- Keywords
- Phase I, AROG4-01, mesothelioma, solid tumors, NSCLC, ovarian cancer, colorectal cancer, dose escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Aromics TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2025 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 22 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if drug AROG4-01 is safe in patients with solid tumors who have no available treatment alternative. Different doses will be tested in order to identify the most suitable one. Once it is identiffied, up to 20 patients will be treated with that dose, to check if thye get clinical benefit.
Participants will: receive intravenous administrations of ARG4-01 twice weekly, and visit the clinic twice every week for checkups and tests.
Detailed description
This study is an open label, Phase 1 dose escalation trial with two expansion cohorts to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of AROG4-01 in patients with mesothelioma and other advanced solid tumors.
This clinical trial is divided into two parts: dose escalation (part A), and dose expansion (part B).
Dose escalation In the present trial, patients will be enrolled sequentially into escalating dose cohorts, and will continue receiving AROG4-01 until disease progression, unacceptable toxicity, withdrawal of consent or otherwise as specified in the investigational medicinal product (IMP) discontinuation criteria.
Patients in a dose cohort will receive AROG4-01 as intravenous (IV) administrations at the same dose in a dosing interval of twice a week, four weeks (equal to one cycle) consecutively without interruption, except when necessary to manage adverse events (AEs).
Six cohorts at escalating dose levels are envisaged. Dose escalation may continue beyond, until the recommended for part B dose, which will be the recommended for phase 2 dose (RP2D), can be defined based on safety, preliminary efficacy, PK and PD data, based on the recommendations of the Safety Review Committee (SRC). The RP2D is defined as the recommended for phase 2 dose, but two cohorts will be treated as part of the phase 1 expansion with that particular dose, in order to get more safety and efficacy data.
Escalation to the next dose level will occur following the SRC meeting for the most recently completed cohort. In considering the appropriate dose level for the next cohort the following will be applied:
- The maximum dose increment will be limited to 100% if patients of a given cohort experience one Grade ≥ 2 AE during the DLT period or if at least one patient decreases >10% weight.
- The maximum dose increment will be limited to 50% if a patient of a given cohort experiences one DLT during the DLT period.
If the prior circumstances do not occur, dose escalation will continue at higher increments (not exceeding three times prior dose level), as determined by the SRC.
Extension phase At the dose expansion part, two cohorts of patients with advanced solid tumor each will be recruited. One cohort of patients with advanced MPM (cohort 1) and a second cohort of patients with other solid tumors (cohort 2). Patients will be treated with AROG4-01 at the RP2D of AROG4-01 resulting from part A.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This clinical trial is divided into two parts: dose escalation (part A), and dose expansion (part B). In part A (dose escalation), patients will be treated with AROG4-01 at different doses, starting at 9 mg/m2. Escalation to next dose levels will occur following the Safety Review Committee meeting for the most recently completed cohort. The MTD decided as per part A (dose escalation) will be used for part B (dose expansion).
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: AROG4-01Four dose levels will be tested. If there are no safety concerns, dose escalation may continue with up to two additional dose levels |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female patients, 18 years or older, with a diagnosis (histology or citology) of advanced (unresectable or metastatic) solid tumor for which there is no curative therapy, has progressed on SOC treatment or for whom SOC is no longer an option. In part B patients will be included in different cohorts according to the histology (mesothelioma vs. non-mesothelioma).
- Evaluable (part A) or measurable disease (part B) as per RECIST v1.1 (part A) or mRECIST v1.1. (part B). Progressive disease to the on or following the last line of antitumor treatment.
- ECOG performance status ≤ 2.
- Life expectancy ≥12 weeks.
- Hematology and clinical chemistry laboratory parameters within acceptable ranges.
Key exclusion criteria (9 listed)
- Systemic anti-cancer therapy within 4 weeks prior to study admission.
- Radiation therapy within 4 weeks prior to study entry.
- Any major surgery within 4 weeks before first dose of study treatment No major surgery must be planned during the trial expected treatment. receiving study treatment. Participants with recent surgery with only local anesthesia may be included.
- Non-malignant systemic disease including cerebrovascular accident, myocardial infarction in the last 6 months, unstable angina pectoris, unstable cardiac arrhythmia, New York Heart Association (NYHA) Class III or IV heart failure, coagulation abnormalities and clinically significant pulmonary compromise, .
- Left ventricular ejection fraction below institutional normal limits.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AROG4-01Also: Dose level 2, Dose level 3, Dose level 4, Dose level 5AROG4-01 will be administered as IV infusions in biweekly dosing interval. The first dosing day will be Day 1, 28 days cycle. | Drug | Dose escalation |
| AROG4-01AROG4-01 will be administered as IV infusions in biweekly dosing interval. The first dosing day will be Day 1, 28 days cycle. This study is an open label, Phase 1 dose escalation trial with two expansion cohorts. The study consists of two parts: * Part A: Dose escalation in patients with advanced solid tumors. Approximately 8 to 20 patients in total will be enrolled in part A, covering up to 6 dose levels. * Part B: At the dose expansion phase, AROG4-01 two cohorts of ten patients with advanced solid tumor each will be recruited. One cohort of patients with advanced MPM (cohort 1) and a second cohort of patients with other solid tumors (cohort 2). | Drug | Dose escalation |
Primary outcome
To evaluate the safety and tolerability of AROG4-01
Time frame: 12 months
To evaluate the safety and tolerability of AROG4-01 in adult patients with advanced solid tumors, including determination of the main DLT associated to AROG4-01. To assess the MTD (RP2D) defined as the highest dose at which no more than one in six patients experience a AROG4-01-related DLT. DLTs will be evaluated after the first treatment cycle.
3 secondary outcomes
To assess the preliminary antitumor activity of AROG4-01 monotherapy as measured by Overall Response Rate (ORR) according to standard criteria (RECIST 1.1 [18] or mRECIST v1.1
Time frame: 24 months
To characterize the PK of AROG4-01.
Time frame: 24 months
To characterize the PK of AROG4-01
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Background: PubMed 32708710Aubets E, J Felix A, Garavis M, Reyes L, Avino A, Eritja R, Ciudad CJ, Noe V. Detection of a G-Quadruplex as a Regulatory Element in Thymidylate synthase for Gene Silencing Using Polypurine Reverse Hoogsteen Hairpins. Int J Mol Sci. 2020 Jul 16;21(14):5028. doi: 10.3390/ijms21145028.
- Background19- Phan, A. T., & Patel, D. J. (2005). "RNA tetraplexes, structures and functions." Biochemistry, 44(2), 639-649. doi:10.1021/bi048804m
- BackgroundSimon, J. S., et al. (2018). "Hairpin structures near G-quadruplexes can modulate G4 stability and drug binding." Nature Communications, 9, 4621. doi:10.1038/s41467-018-07055-8
- Background: PubMed 26350216Rhodes D, Lipps HJ. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res. 2015 Oct 15;43(18):8627-37. doi: 10.1093/nar/gkv862. Epub 2015 Sep 8.
- Company websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AROG4-01 in people with Solid Tumors (Phase 1) and Mesothelioma, run by Aromics Therapeutics.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carme Plasencia, PhD (+34 670 594 309, carme.plasencia@aromics.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety and tolerability of AROG4-01 (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06652529, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.