Advanced CancerPhase 1NCT04336124
Safety and Pharmacokinetic Study of CVM-1118 Extended-Release in Advanced Cancer Patients
A Phase 1 study testing CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule) in people with Advanced Cancer, run by TaiRx, Inc. at 2 sites in Taiwan.
Trial summary
CVM-1118 Immediate-release (IR) Capsule and CVM-1118 Extended-release (ER) Capsule are proprietary oncology products developed by TaiRx, Inc. for the treatment of patients suffering from advanced cancer. Read more about this study
- Who is it for?
- Ages 20 to 99 years
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesTaiwan
- Study dates
- 25 May 2020to 8 Apr 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 20 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Tumor eligibility:
- Histologically or cytologically confirmed advanced malignancies, which is refractory to standard of care therapy, or for whom no standard of care therapy is available.
- Solid tumors must have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1). Target lesions that have been previously irradiated will not be considered measurable (lesion) unless increase in size is observed following completion of radiation therapy. Lymphomas must have measurable disease as per Revised Response Criteria for Malignant Lymphomas.
- ECOG performance status 0 to 2. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade 1 (except alopecia).
- Adequate organ function as defined by the following criteria:
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤3 x upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to underlying malignancy
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- Total serum bilirubin ≤1.5 x ULN (except for patients with documented Gilbert's syndrome)
- Absolute neutrophil count (ANC) 1,500/µL
- Platelets 90,000/µL
- Hemoglobin 9.0 g/dL
- Serum creatinine ≤1.5 x ULN or creatinine clearance of ≥ 60 mL/min
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the study prior to enrollment.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Patients presenting with any of the following will not be included in the study:
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of starting study treatment.
- Prior high-dose chemotherapy requiring hematopoietic stem cell rescue except for patients with lymphoma
- Current treatment on another clinical study.
- Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks.
- Any of the following within 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack; within 6 months prior to starting study treatment for pulmonary embolus. However, upon agreement between the investigator and sponsor, the 6-month post-event-free period for a patient with a pulmonary embolus can be waived if due to advanced cancers. Appropriate treatment with anticoagulants is permitted.
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- Hypertension that cannot be controlled by medications (>160/100 mmHg despite optimal medical therapy).
- Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO daily is allowed).
- Known human immunodeficiency virus infection.
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) with evidence of chronic active disease or receiving/requiring antiviral therapy.
- History of receiving organ transplantation or immune disorders that require continuous immunosuppressant agent therapy.
- Pregnancy or breastfeeding. Female patients must be surgically sterile or be post-menopausal or must agree to the use of effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, which would make the patient inappropriate for entry into this study.
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
China Medical University Hospital
Taichung
National Cheng Kung University Hospital
Tainan, 704
About this study
Official title: A Phase I Safety and Pharmacokinetic Study of CVM-1118 Extended-Release Capsules Administered Orally to Patients With Advanced Cancers
CVM-1118 Immediate-release (IR) Capsule and CVM-1118 Extended-release (ER) Capsule are proprietary oncology products developed by TaiRx, Inc. for the treatment of patients suffering from advanced cancer. Due to the short elimination half-life of CVM-1118 IR capsules, the extended release (ER) formulation, containing mini-tablets in hard capsule, has been developed to prolong the drug absorption and longer exposure after oral administration. The designed dose of CVM-1118 ER was 200 mg per capsule to provide a more patient-compliant and safe dosage of CVM-1118. The clinical study CVMEX-001 is therefore designed to evaluate the safety and pharmacokinetics of CVM-1118 extend release (ER) Capsule (200 mg/capsule) in patients with advanced cancer.
Read the detailed description
The CVM-1118 ER Capsule will be orally administered BID or TID before meal in 28-day treatment cycles. Patients will receive 400, 600, 800 to 1,200 mg of CVM-1118 ER Capsule in sequential cohort based on safety and dose tolerability. A single-patient cohort per dose level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800 mg/day. Within the first two cohorts, if any Grade 2 or greater toxicity at least possibly attributable to CVM-1118 ER capsule is reported in the first patient during first cycle, a single-patient cohort will be converted to conventional 3+3 study design once and expand to a minimum of 3 evaluable patients for assessment of toxicity within the first cycle. Dose escalation will occur until DLT occurs in 2 or more patients within a dose level. In any cohort, if 1 patient experiences a DLT, 3 additional patients will be enrolled to that dose level. If 2 or more patients experience a DLT, no further dose escalation will occur. Plasma pharmacokinetics samples will be collected at pre-determined time-points for all patients participating in the dose-escalation study.
This study will be completed and closed once the MTD is determined for CVM-1118 ER capsules. However, at the end of 4 cycles, it is recommended that some patients should continue receiving the clinical benefit from CVM-1118 ER capsules. Thus, patients may be continuously treated at the assigned dose level or next higher dose level provided it has been shown to be safe in a previously treated cohort by safety committee, until the treating physician feels the patient is no longer benefiting from the treatment, or CVM-1118 ER Capsule becomes commercially available, as applicable in the country in which the patient lives. In the event of unacceptable toxicity at a given dose, CVM-1118 can be reduced to the previous dose level or suggested lower dose by PI. If unacceptable toxicity persists despite 2 dose reductions, the patient should be removed from study.
- Conditions
- Advanced Cancer
- Being tested
- CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)
- Keywords
- Oncology, Advanced Solid Malignancy, Tumor Response, Safety and pharmacokinetics
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)Drug
Also called TRX-818 ER
Patients will receive initial dose regimen: 400 mg of CVM-1118 ER Capsule per day (200 mg BID) in a 28-day cycle for 4 cycles.
Dose escalates from 400, 600, 800, to 1200 mg of CVM-1118 ER capsules with either BID or TID dosing.
A single-patient cohort per dose level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800 mg/day.
If 2 or more patients experience a DLT, no further dose escalation will occur.
| Study group | Role | What they receive |
|---|---|---|
| CVM-1118 ER | Experimental | Dose escalation (escalation from 400, 600, 800 to 1200 mg of CVM-1118 ER Capsule) Receives: Drug: CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) of CVM-1118 ER Capsule
Dose escalation will occur until DLT occurs in 2 or more patients within a dose level. In any cohort, if 1 patient experiences a DLT, 3 additional patients will be enrolled to that dose level. If 2 or more patients experience a DLT, no further dose escalation will occur.
Measured: up to 28 days
Maximum tolerated dose (MTD) of CVM-1118 ER Capsule
The MTD will be defined as the dose level at which at most one of six patients experiences a DLT after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT. The Safety Committee may expand the cohort beyond six patients to better define the safety profile of this cohort in the search for the MTD.
Measured: up to 28 days
Secondary outcomes (6)
Preliminary assessment of anti-tumor activity of CVM-1118 ER Capsule
RECIST 1.1 for solid tumor and Revised Response Criteria for Malignant Lymphoma
Measured: up to 56 days
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include AUC(0-last)
AUC(0-last): area under the plasma concentration versus time curve to the time of the last measurable concentration
Measured: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include Cmax
Cmax: Maximum plasma concentration
Measured: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include Tmax
Tmax: Time to maximum plasma concentration
Measured: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include T(1/2)
T(1/2): Terminal elimination half-life
Measured: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Time to tumor progression (TTP)
Time to progression (TTP) is defined as the time from the first dose of study drug to the time of progression
Measured: up to 112 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2020
- Study start25 May 2020
- Primary completion8 Feb 2021
- Study completion8 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- TaiRx, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wu-Chou Su, M.D., Principal investigator, National Cheng Kung University Hospital,TaiwanLi-Yuan Bai, M.D., Principal investigator, China Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04336124
- Sponsor's protocol ID
- CVMEX-001
- Status last verified
- Nov 2022
- First submitted
- 31 Mar 2020
- Last updated
- 28 Nov 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Safety and Pharmacokinetic Study of CVM-1118 Extended-Release Capsules Administered Orally to Patients With Advanced Cancers
- ClinicalTrials.gov ID
- NCT04336124
- Acronym / sponsor ID
- CVMEX-001
- Conditions
- Advanced Cancer
- Keywords
- Oncology, Advanced Solid Malignancy, Tumor Response, Safety and pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- TaiRx, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 May 2020 (actual)
- Primary completion
- 8 Feb 2021 (actual)
- Study completion
- 8 Apr 2022 (actual)
- First posted
- 7 Apr 2020 (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.
CVM-1118 Immediate-release (IR) Capsule and CVM-1118 Extended-release (ER) Capsule are proprietary oncology products developed by TaiRx, Inc. for the treatment of patients suffering from advanced cancer. Due to the short elimination half-life of CVM-1118 IR capsules, the extended release (ER) formulation, containing mini-tablets in hard capsule, has been developed to prolong the drug absorption and longer exposure after oral administration. The designed dose of CVM-1118 ER was 200 mg per capsule to provide a more patient-compliant and safe dosage of CVM-1118. The clinical study CVMEX-001 is therefore designed to evaluate the safety and pharmacokinetics of CVM-1118 extend release (ER) Capsule (200 mg/capsule) in patients with advanced cancer.
Detailed description
The CVM-1118 ER Capsule will be orally administered BID or TID before meal in 28-day treatment cycles. Patients will receive 400, 600, 800 to 1,200 mg of CVM-1118 ER Capsule in sequential cohort based on safety and dose tolerability. A single-patient cohort per dose level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800 mg/day. Within the first two cohorts, if any Grade 2 or greater toxicity at least possibly attributable to CVM-1118 ER capsule is reported in the first patient during first cycle, a single-patient cohort will be converted to conventional 3+3 study design once and expand to a minimum of 3 evaluable patients for assessment of toxicity within the first cycle. Dose escalation will occur until DLT occurs in 2 or more patients within a dose level. In any cohort, if 1 patient experiences a DLT, 3 additional patients will be enrolled to that dose level. If 2 or more patients experience a DLT, no further dose escalation will occur. Plasma pharmacokinetics samples will be collected at pre-determined time-points for all patients participating in the dose-escalation study.
This study will be completed and closed once the MTD is determined for CVM-1118 ER capsules. However, at the end of 4 cycles, it is recommended that some patients should continue receiving the clinical benefit from CVM-1118 ER capsules. Thus, patients may be continuously treated at the assigned dose level or next higher dose level provided it has been shown to be safe in a previously treated cohort by safety committee, until the treating physician feels the patient is no longer benefiting from the treatment, or CVM-1118 ER Capsule becomes commercially available, as applicable in the country in which the patient lives. In the event of unacceptable toxicity at a given dose, CVM-1118 can be reduced to the previous dose level or suggested lower dose by PI. If unacceptable toxicity persists despite 2 dose reductions, the patient should be removed from study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CVM-1118 ER | Experimental | Drug: CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)Dose escalation (escalation from 400, 600, 800 to 1200 mg of CVM-1118 ER Capsule) |
Who may qualify
- Ages
- 20 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Tumor eligibility:
- Histologically or cytologically confirmed advanced malignancies, which is refractory to standard of care therapy, or for whom no standard of care therapy is available.
- Solid tumors must have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1). Target lesions that have been previously irradiated will not be considered measurable (lesion) unless increase in size is observed following completion of radiation therapy. Lymphomas must have measurable disease as per Revised Response Criteria for Malignant Lymphomas.
- ECOG performance status 0 to 2. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade 1 (except alopecia).
- Adequate organ function as defined by the following criteria:
Key exclusion criteria (13 listed)
- Patients presenting with any of the following will not be included in the study:
- Any of the following within 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack; within 6 months prior to starting study treatment for pulmonary embolus. However, upon agreement between the investigator and sponsor, the 6-month post-event-free period for a patient with a pulmonary embolus can be waived if due to advanced cancers. Appropriate treatment with anticoagulants is permitted.
- Hypertension that cannot be controlled by medications (>160/100 mmHg despite optimal medical therapy).
- Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO daily is allowed).
- Known human immunodeficiency virus infection.
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 |
|---|---|---|
| CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)Also: TRX-818 ERPatients will receive initial dose regimen: 400 mg of CVM-1118 ER Capsule per day (200 mg BID) in a 28-day cycle for 4 cycles. Dose escalates from 400, 600, 800, to 1200 mg of CVM-1118 ER capsules with either BID or TID dosing. A single-patient cohort per dose level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800 mg/day. If 2 or more patients experience a DLT, no further dose escalation will occur. | Drug | CVM-1118 ER |
Primary outcome
Dose limiting toxicity (DLT) of CVM-1118 ER Capsule
Time frame: up to 28 days
Dose escalation will occur until DLT occurs in 2 or more patients within a dose level. In any cohort, if 1 patient experiences a DLT, 3 additional patients will be enrolled to that dose level. If 2 or more patients experience a DLT, no further dose escalation will occur.
Maximum tolerated dose (MTD) of CVM-1118 ER Capsule
Time frame: up to 28 days
The MTD will be defined as the dose level at which at most one of six patients experiences a DLT after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT. The Safety Committee may expand the cohort beyond six patients to better define the safety profile of this cohort in the search for the MTD.
6 secondary outcomes
Preliminary assessment of anti-tumor activity of CVM-1118 ER Capsule
Time frame: up to 56 days
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include AUC(0-last)
Time frame: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include Cmax
Time frame: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include Tmax
Time frame: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include T(1/2)
Time frame: Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose
Time to tumor progression (TTP)
Time frame: up to 112 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2022.
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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. This study is not recruiting at the moment.
Wu-Chou Su, M.D. principal investigator
National Cheng Kung University Hospital,Taiwan
Li-Yuan Bai, M.D. principal investigator
China Medical University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule) in people with Advanced Cancer, run by TaiRx, Inc. at 2 sites in Taiwan.
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 13 inclusion and 13 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: finished, as of the sponsor's last update on 28 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) of CVM-1118 ER Capsule (time frame: up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Nov 2022; AzTrials last refreshed its copy on 7 Nov 2026.