Solid TumorPhase 1NCT03990454
Safety Study of SLC-391 in Subjects With Solid Tumors
A Phase 1 study testing SLC-391 in people with Solid Tumor, run by SignalChem Lifesciences Corporation at 3 sites in Canada.
Trial summary
SLC-391 is a novel, potent and specific small molecule inhibitor of receptor tyrosine kinase AXL with desirable potency and pharmaceutical properties. It has demonstrated antiproliferative activity against different tumour cell lines in vitro and efficacy in different animal models including nonsmall cell lung cancer… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- SLC-391
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 3 sitesCanada
- Study dates
- 17 Sep 2019to 30 Jun 2023
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be 18 years of age or older at the time of signing the informed consent.
- Have a histologically or cytologically confirmed diagnosis of a solid tumour malignancy that is advanced and/or metastatic or unresectable and for which standard or curative measures do not exist or are no longer effective.
- Have measurable disease as per the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or as per a modified RECIST, if applicable.
- Have a performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- Be able to ingest oral medication.
- Have adequate organ function,
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- Have recovered to ≤ grade 1 from the effects of any prior cancer therapy, except for alopecia; irreversible neuropathy should have recovered to ≤ grade 2. Toxic effects also include laboratory test abnormalities.
- Be afebrile at baseline prior to SLC-391 administration (ie, < 38.0 °C).
- Have a life expectancy greater than 3 months, in the Investigator's opinion.
- The following time must have elapsed between previous therapy for cancer and first dose of SLC-391:
- At least 4 weeks since previous cancer-directed therapy, including investigational agents or devices (cytotoxic agents, targeted therapy including monoclonal antibodies, immunotherapy, hormonal therapy, and prior radiotherapy) with the exception of nitrosoureas/mitomycin where 6 weeks since these therapies.
- At least 4 weeks or 5 times the elimination half-life (whichever is shortest) of any investigational agents, including drugs, biologics, or combination products.
- At least 4 weeks since any major surgery.
- Sexually active women of child-bearing potential and sexually active male subjects with a female partner of child-bearing potential or pregnant must agree to use acceptable methods of contraception to avoid pregnancy from screening, for the duration of the study, and for 3 months after the last dose of study drug. Male subjects must also agree to refrain from donating sperm for the duration of the study, including during dose interruptions and for 3 months after the last dose administered.
- Be able and willing to provide signed informed consent and comply with the requirements, assessment schedule, dosing schedule, and restrictions listed in the informed consent form (ICF) and study protocol.
Who cannot join
- Prior use of any AXL inhibitor
- Localised or metastatic prostate cancer subjects who are concurrently receiving abiraterone or enzalutamide. Those subjects on stable (>3 months) anti-cancer hormonal therapy are allowed.
- Refractory nausea and vomiting, chronic gastrointestinal (GI) diseases, GI bleeding, ulceration, or perforation within 12 weeks prior to the first dose of the study drug, or significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of the study drug.
- History of myocardial infarction, unstable angina, congestive heart failure (New York Heart Association class ≥ III/IV), cerebrovascular accident, transient ischaemic attack, limb claudication at rest, stroke or subarachnoid hemorrhage, coagulopathy, deep vein thrombosis, pulmonary embolism in the 3 months prior to consent.
- Uncontrolled hypertension (≥ 160/100 mmHg).
- History of or ongoing symptomatic dysrhythmias, uncontrolled atrial or ventricular arrhythmias, or heart block (excluding 1st degree block, consisting of PR interval prolongation only). Controlled atrial fibrillation is allowed.
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- QTcF interval > 480 msec.
- Severe respiratory illness that significantly impacts functional status in daily life including a known history of active tuberculosis (Mycobacterium tuberculosis).
- History of significant weight loss (≥ 7 kgs/15 lbs) within 4 weeks prior to the first dose of study drug.
- History of primary immunodeficiency or those with known human immunodeficiency virus (HIV), or known active hepatitis B (HBV; including core antibody and surface antigen; AntiHBc and HBsAg, respectively) or hepatitis C (HCV) infection. Note: No testing for HIV, Hepatitis B or C is required unless mandated by a local health authority.
- Active uncontrolled infection, or an unstable or severe intercurrent medical condition that requires treatment.
- History of solid organ transplant or bone marrow transplant.
- Any condition or illness that, in the opinion of the Investigator, would compromise subject safety or interfere with the evaluation of the safety of the study drug and jeopardises compliance with the protocol and study visits.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- History of prior malignancy, except for the following: curatively treated basal or squamous cell carcinoma of the skin (nonmelanoma skin cancer); cervical or vaginal intra-epithelial neoplasia; or noninvasive breast cancer in situ at screening. Subjects with other curatively treated malignancies who have had no evidence of metastatic disease and a > 2-year disease-free interval may be enrolled after approval by the Medical Monitor or SignalChem Lifesciences (SLC) designee.
- Females who are pregnant, planning to become pregnant, or breastfeeding.
- Hypersensitivity to the study drug or excipients (lactose, microcrystalline cellulose, magnesium stearate, and gelatin capsule shell).
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2
The Ottawa Hospital Cancer Center
Ottawa, Ontario, K1H 8L6
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1, Open-label, Dose-escalationStudy of the Safety and Pharmacokinetics of the AXL Inhibitor SLC-391 Administered Orally to Subjects With Solid Tumours
SLC-391 is a novel, potent and specific small molecule inhibitor of receptor tyrosine kinase AXL with desirable potency and pharmaceutical properties. It has demonstrated antiproliferative activity against different tumour cell lines in vitro and efficacy in different animal models including nonsmall cell lung cancer (NSCLC), chronic myeloid leukemia (CML) and (acute myeloid leukemia (AML) models. It has also exhibited strong synergy with other approved targeted therapies in different animal models.
This is the first clinical study with SLC-391. The goals of this study are to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic profile of SLC-391, and then to identify a safe and pharmacologically active dose for evaluation in subsequent cohorts or clinical studies. In addition, change from baseline of possible blood biomarkers (soluble AXL and Gas 6) may be evaluated.
This is an open-label, multicentre, phase 1, dose-escalation, first in human study to evaluate the safety of SLC-391 administered orally (once or twice daily) in 21-day cycles to subjects with advanced solid tumours.
- Conditions
- Solid Tumor
- Being tested
- SLC-391
- Keywords
- AXL Inhibitor, Solid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLC-391Drug
SLC-391 is an AXL inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | The starting dose will be 25 mg/day and subsequent doses will be determined after an internal review by Data Review Committee of all available safety, PK and PD data from the minimum required number of subjects who complete cycle 1. All dose-escalation decisions and the rationale for progressing to the next cohort will be documented.
A subject may continue treatment with SLC-391 in 21-day cycles until the treatment discontinuation criteria are met. Receives: Drug: SLC-391 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events (AEs) as assessed by NCI-CTCAE v5.0
To assess AEs as criteria of safety of oral SLC-391
Measured: 2 years
Maximum Tolerated Dose of SLC-391
To determine the maximum tolerated dose (MTD) of SLC-391
Measured: 21 days
Secondary outcomes (10)
Area under the plasma concentration versus time curve (AUC) of SLC-391
Changes in AUC over time in subjects taking SLC-391 once or twice daily.
Measured: Day 1 predose through to Day 21 post-final dose
Maximum Observed Plasma Concentration (Cmax)
Cmax is the maximum observed plasma concentration in ng/mL
Measured: Day 1 predose through to Day 21 post-final dose
Time to the Maximum Observed Plasma Concentration (Tmax)
Tmax is the time in hours to reach Cmax following dosing
Measured: Day 1 predose through to Day 21 post-final dose
Terminal elimination half-life (t1/2)
The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase
Measured: Day 1 predose through to Day 21 post-final dose
Recommended Dose of SLC-391 for future trials
Determine the recommended phase 2 dose (RP2D) of SLC-391
Measured: 2 years
Preliminary efficacy of SLC-391
Determine tumour response defined by the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 to SLC-391
Measured: 2 years
Number of Participants with Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory investigation includes hematology, biochemistry, urinalysis, and Serology.
Measured: 2 years
Number of Participants with Clinically Significant Changes From Baseline in Vital Signs
Vital sign measurements includes blood pressure, heart rate, respiratory temperature, and oral temperature.
Measured: 2 years
Number of Participants with Clinically Significant Changes From Baseline in electrocardiogram (ECGs) Findings
ECG parameters includes heart rate, PR interval, QRS, QT, and QTcF.
Measured: 2 years
Number of Participants with Clinically Significant Changes From Baseline in physical examinations
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start17 Sep 2019
- Primary completion30 Jun 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies 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
- The study will employ a 3+3 dose-escalation design. Cohorts (same dose level) of 3 to 6 evaluable subjects will participate in a dose-escalation scheme in which the dose of SLC-391 will be increased in each consecutive cohort. Evaluation of a cohort of ≥ 3 subjects that have completed a 21-day cycle (cycle 1) is required prior to defining a new SLC-391 dose and schedule for the next cohort. Dose-escalation decisions by the Data Review Committee will take into account all available data including PK/pharmacodynamic data and the safety profile of prior cohorts. Based on all available emerging data, alternative dosing schedules, frequency, or dose reductions may be considered.
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- SignalChem Lifesciences Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zaihui Zhang, PhD, Study director, SignalChem Lifesciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03990454
- Sponsor's protocol ID
- SLC-391-101
- Status last verified
- Aug 2023
- First submitted
- 14 Jun 2019
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Dose-escalationStudy of the Safety and Pharmacokinetics of the AXL Inhibitor SLC-391 Administered Orally to Subjects With Solid Tumours
- ClinicalTrials.gov ID
- NCT03990454
- Acronym / sponsor ID
- SLC-391-101
- Conditions
- Solid Tumor
- Keywords
- AXL Inhibitor, Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- SignalChem Lifesciences CorporationIndustry (pharma, biotech, devices)
- Study start
- 17 Sep 2019 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 19 Jun 2019 (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.
SLC-391 is a novel, potent and specific small molecule inhibitor of receptor tyrosine kinase AXL with desirable potency and pharmaceutical properties. It has demonstrated antiproliferative activity against different tumour cell lines in vitro and efficacy in different animal models including nonsmall cell lung cancer (NSCLC), chronic myeloid leukemia (CML) and (acute myeloid leukemia (AML) models. It has also exhibited strong synergy with other approved targeted therapies in different animal models.
This is the first clinical study with SLC-391. The goals of this study are to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic profile of SLC-391, and then to identify a safe and pharmacologically active dose for evaluation in subsequent cohorts or clinical studies. In addition, change from baseline of possible blood biomarkers (soluble AXL and Gas 6) may be evaluated.
This is an open-label, multicentre, phase 1, dose-escalation, first in human study to evaluate the safety of SLC-391 administered orally (once or twice daily) in 21-day cycles to subjects with advanced solid tumours.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study will employ a 3+3 dose-escalation design. Cohorts (same dose level) of 3 to 6 evaluable subjects will participate in a dose-escalation scheme in which the dose of SLC-391 will be increased in each consecutive cohort. Evaluation of a cohort of ≥ 3 subjects that have completed a 21-day cycle (cycle 1) is required prior to defining a new SLC-391 dose and schedule for the next cohort. Dose-escalation decisions by the Data Review Committee will take into account all available data including PK/pharmacodynamic data and the safety profile of prior cohorts. Based on all available emerging data, alternative dosing schedules, frequency, or dose reductions may be considered.
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: SLC-391The starting dose will be 25 mg/day and subsequent doses will be determined after an internal review by Data Review Committee of all available safety, PK and PD data from the minimum required number of subjects who complete cycle 1. All dose-escalation decisions and the rationale for progressing to the next cohort will be documented. A subject may continue treatment with SLC-391 in 21-day cycles until the treatment discontinuation criteria are met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Be 18 years of age or older at the time of signing the informed consent.
- Have a histologically or cytologically confirmed diagnosis of a solid tumour malignancy that is advanced and/or metastatic or unresectable and for which standard or curative measures do not exist or are no longer effective.
- Have measurable disease as per the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or as per a modified RECIST, if applicable.
- Have a performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- Be able to ingest oral medication.
Key exclusion criteria (17 listed)
- Prior use of any AXL inhibitor
- Localised or metastatic prostate cancer subjects who are concurrently receiving abiraterone or enzalutamide. Those subjects on stable (>3 months) anti-cancer hormonal therapy are allowed.
- Refractory nausea and vomiting, chronic gastrointestinal (GI) diseases, GI bleeding, ulceration, or perforation within 12 weeks prior to the first dose of the study drug, or significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of the study drug.
- History of myocardial infarction, unstable angina, congestive heart failure (New York Heart Association class ≥ III/IV), cerebrovascular accident, transient ischaemic attack, limb claudication at rest, stroke or subarachnoid hemorrhage, coagulopathy, deep vein thrombosis, pulmonary embolism in the 3 months prior to consent.
- Uncontrolled hypertension (≥ 160/100 mmHg).
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 |
|---|---|---|
| SLC-391SLC-391 is an AXL inhibitor | Drug | Dose escalation |
Primary outcome
Number of Participants with Adverse Events (AEs) as assessed by NCI-CTCAE v5.0
Time frame: 2 years
To assess AEs as criteria of safety of oral SLC-391
Maximum Tolerated Dose of SLC-391
Time frame: 21 days
To determine the maximum tolerated dose (MTD) of SLC-391
10 secondary outcomes
Area under the plasma concentration versus time curve (AUC) of SLC-391
Time frame: Day 1 predose through to Day 21 post-final dose
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 predose through to Day 21 post-final dose
Time to the Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 1 predose through to Day 21 post-final dose
Terminal elimination half-life (t1/2)
Time frame: Day 1 predose through to Day 21 post-final dose
Recommended Dose of SLC-391 for future trials
Time frame: 2 years
Preliminary efficacy of SLC-391
Time frame: 2 years
Number of Participants with Clinically Significant Changes From Baseline in Laboratory Parameters
Time frame: 2 years
Number of Participants with Clinically Significant Changes From Baseline in Vital Signs
Time frame: 2 years
Number of Participants with Clinically Significant Changes From Baseline in electrocardiogram (ECGs) Findings
Time frame: 2 years
Number of Participants with Clinically Significant Changes From Baseline in physical examinations
Time frame: 2 years
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 18 Aug 2023.
- Individual participant dataSharing planned: No
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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.
Zaihui Zhang, PhD study director
SignalChem Lifesciences Corporation
3 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 SLC-391 in people with Solid Tumor, run by SignalChem Lifesciences Corporation at 3 sites in Canada.
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 15 inclusion and 17 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 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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?
Number of Participants with Adverse Events (AEs) as assessed by NCI-CTCAE v5.0 (time frame: 2 years). 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 18 Aug 2023.