Solid TumorPhase 1NCT02968485
Phase I Study of SHR7390 in Patients With Advanced Solid Tumors
A Phase 1 study testing SHR7390 in people with Solid Tumor, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
Trial summary
This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors. To evaluate the pharmacokinetics of SHR7390 in patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Solid Tumor
- What is being tested?
- SHR7390
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- Nov 2016to Jul 2019
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The study is open to all males and females who meet the following inclusion criteria at screening and baseline to participate in the study.
- To be included to participate in this study each patient must:
- 18-70 years of age, both women and men;
- invalid the standard treatment or non standard and effective treatment in patients with advanced solid tumors diagnosed by pathology;
- the Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS) of 0-1;
- the expected lifetime ≥ 3 months;
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- organ function you must meet the following requirements:
- Adequate bone marrow reserve: including neutrophil absolute count,platelets and hemoglobin;
- Liver: serum albumin ≥ 3.0 g/dl; bilirubin, Alanine aminotransferase（ALT）and aspartate aminotransferase（AST）≤ 1.5 x upper limit of normal value (ULN),if there is liver metastasis, the ALT or AST
- 5x upper limit of normal value (ULN);
- Kidneys: creatinine clearance ≥ 50 mL/min (Cockcroft-Gault of the standard formula）；
- Heart: left ventricular ejection fraction ≥ 50%; normal Electrocardiograph (ECG) and corrected QT interval（QTc）;
- The damage of the patients caused by other treatments has been restored;
- A agreement to use a highly effective, non-hormonal form of contraception is required for women of childbearing potential and men with partners of childbearing potential, who were not sterilized surgically, for duration of the study treatment and after the last dose of study treatment; For female patients of child bearing potential,who was not sterilized surgically,the serum human chorionic gonadotropin （HCG） pregnancy test must be the negative
- Written informed consent is provided by signing the informed consent form.
Who cannot join
- Subjects who meet any of the criteria listed below will not be eligible for participation in this study. A patient will not be eligible for study participation if:
- Previous treatment with other protein kinase MEK inhibitors;
- Use of other investigational anti-cancer drugs or the termination of the investigational drugs within the last four weeks;
- Currently or possibly receiving other cancer therapy during the study period;
- Presence of a factor that influences the oral drug (such as inability to swallow) or presence of active gastrointestinal disease or other conditions that will interfere significantly with the absorption, distribution, metabolism, or excretion of drug;
- History of retinal vascular occlusion （RVO） or central serous retinopathy;
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- Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis or central serous retinopathy;
- Intraocular pressure>21mmHg as measured by tonography or glaucoma;
- Tumor metastases of central nervous system or leptomeningeal metastases. primary malignancy of the central nervous system;
- Evidence of severe or uncontrolled systemic diseases (e.g. unstable or uncompensated respiratory, hepatic, renal or cardiac diseases);
- History of acute coronary syndromes (including unstable angina);
- Presence of arrhythmia, myocardial ischemia with drug intervention. III-IV stage heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Medical treatment for an acute phase of infection;
- hepatitis B virus（HBV) or hepatitis C virus (HCV) infection stage with abnormal liver function;
- History of immunodeficiency, or other acquired and congenital immunodeficiency disease;
- Psychological, familial, sociological or geographical conditions that do not permit compliance with protocol;
- Unwillingness or inability to follow the procedures outlined in the protocol;
- Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol;
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The Cancer Center,Sun Yat-sen University
Guangzhou, Guangdong, 510060
RuiHua Xu, MD, PhD, 86-20-87343008, xurh@sysucc.org.cn
About this study
Official title: A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR7390 in Patients With Advanced Solid Tumors
This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors.
To evaluate the pharmacokinetics of SHR7390 in patients with advanced solid tumors.
To study the effects of food on the pharmacokinetic parameters of SHR7390. To assess the antitumor activity of SHR7390 in patients with advanced solid tumors preliminarily and recommend reasonable dosage regimen for the follow-up clinical trial.
Read the detailed description
This is an open-label, dose escalation study of repeated doses of SHR7390 in the patients with advanced solid tumors that have no targeted agent as standard of therapy.
A study cycle is defined as SHR7390 administered once daily orally for 28 days. Dose limiting toxicities (DLT) will be assessed in the first cycle of treatment. the trial is dose escalation and is designed by Accelerated Titration Designs during initial accelerated phase. when the significant toxicity or DLT is observed in any course of treatment,the accelerated titration trial terminates and subsequent cohort sizes and dose escalation are a conventional design of 3+3 patients. If one adverse event （AE） meets dose limiting toxicity (DLT) criteria at a given dose, 3 additional patients will be enrolled in this dose cohort. If 2 DLTs are determined at a given dose level, this dose will be designated as the MTD.
Additional patients will be enrolled for PK evaluations at different dose levels based on preliminary safety and tolerability. Multiple blood samples at designated time points will be collected for PK evaluations.
The safety, tolerability and AEs will be closely monitored throughout the study duration. The preliminary effectiveness and clinical benefits of SHR7390 will be evaluated as a single agent.
The evaluation of the effects of a high-fat, high-calorie meal on the single-dose pharmacokinetics (PK) of SHR7390.The design to assess food-effect is a randomized, balanced, 2-treatment(fed vs. fasted), separated by an adequate wash-out period.
- Conditions
- Solid Tumor
- Being tested
- SHR7390
- Keywords
- advanced solid tumor, Protein Kinase MEK inhibitor (MEKi), Safety, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR7390Drug
Also called MEK inhibitor
SHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg and 0.5 mg. Multiple tablets of SHR7390 will be administered daily to achieve targeted doses of SHR7390: 0.25 mg-4 mg. Tablets will be orally administered with 240 ml water, once daily, 2 hours after a meal.
| Study group | Role | What they receive |
|---|---|---|
| SHR7390 | Experimental | 60 subjects with advanced solid tumors were received single and then multiple oral doses of SHR7390(2 cycles,each cycle 28days). Receives: Drug: SHR7390 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
to assess safety and tolerability of SHR7390 with a maximum tolerated dose (MTD) of SHR7390 in patients with advanced solid tumors
Measured: Day 1 to 28 ( Cycle 1)
Secondary outcomes (20)
The measurement of maximum plasma concentration (Cmax)
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of the area under the plasma concentration-time versus time curve(AUC)
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of elimination half life (T1/2)
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of time of maximum plasma concentration (Tmax)
Measured: Up to 2 cycles(each cycle 28 days)
The Measurement of mean retention time (MRT)
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of apparent volume of distribution (Vd)
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of clearance (Cl)
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of linear Relationship
Measured: Up to 2 cycles(each cycle 28 days)
The measurement of drug accumulation ratio
Measured: Up to 2 cycles(each cycle 28 days)
The comparison of maximum plasma concentration (Cmax) in the fed and fasted states
Measured: 2 weeks
The comparison of the area under the plasma concentration-time versus time curve(AUC) in the fed and fasted states
Measured: 2 weeks
The comparison of elimination half life(T1/2) in the fed and fasted states
Measured: 2 weeks
The comparison of time of maximum concentration (Tmax) in the fed and fasted states
Measured: 2 weeks
The comparison of mean retention time (MRT) in the fed and fasted states
Measured: 2 weeks
The comparison of apparent volume of distribution (Vd）in the fed and fasted states
Measured: 2 weeks
The comparison of clearance (Cl) in the fed and fasted states
Measured: 2 weeks
The comparison of AUC 0-24h in the fed and fasted states
Measured: 2 weeks
The imaging data of the subjects will be evaluated at the ends of cycle 1 and cycle 2 by RECIST1.1 evaluation criteria separately.
Measured: 2 cycles(each cycle 28 days)
Response rate objective (ORR) will be evaluated at the different dose levels
Measured: 2 cycles(each cycle 28 days)
Disease control rate (DCR) will be evaluated at the different dose levels
Measured: 2 cycles(each cycle 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionApr 2019 (estimated)
- Study completionJul 2019 (estimated)
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.
- More trials run by Jiangsu HengRui Medicine Co., Ltd.The sponsor's other registered studies.
- 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- RuiHua Xu, MD, PhD, Principal investigator, The Cancer Center,Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02968485
- Sponsor's protocol ID
- SHR7390-I-101-AST
- Status last verified
- Feb 2018
- First submitted
- 7 Oct 2016
- Last updated
- 15 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR7390 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02968485
- Acronym / sponsor ID
- SHR7390-I-101-AST
- Conditions
- Solid Tumor
- Keywords
- advanced solid tumor, Protein Kinase MEK inhibitor (MEKi), Safety, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Nov 2016
- Primary completion
- Apr 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 18 Nov 2016 (estimated)
- 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.
This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors.
To evaluate the pharmacokinetics of SHR7390 in patients with advanced solid tumors.
To study the effects of food on the pharmacokinetic parameters of SHR7390. To assess the antitumor activity of SHR7390 in patients with advanced solid tumors preliminarily and recommend reasonable dosage regimen for the follow-up clinical trial.
Detailed description
This is an open-label, dose escalation study of repeated doses of SHR7390 in the patients with advanced solid tumors that have no targeted agent as standard of therapy.
A study cycle is defined as SHR7390 administered once daily orally for 28 days. Dose limiting toxicities (DLT) will be assessed in the first cycle of treatment. the trial is dose escalation and is designed by Accelerated Titration Designs during initial accelerated phase. when the significant toxicity or DLT is observed in any course of treatment,the accelerated titration trial terminates and subsequent cohort sizes and dose escalation are a conventional design of 3+3 patients. If one adverse event （AE） meets dose limiting toxicity (DLT) criteria at a given dose, 3 additional patients will be enrolled in this dose cohort. If 2 DLTs are determined at a given dose level, this dose will be designated as the MTD.
Additional patients will be enrolled for PK evaluations at different dose levels based on preliminary safety and tolerability. Multiple blood samples at designated time points will be collected for PK evaluations.
The safety, tolerability and AEs will be closely monitored throughout the study duration. The preliminary effectiveness and clinical benefits of SHR7390 will be evaluated as a single agent.
The evaluation of the effects of a high-fat, high-calorie meal on the single-dose pharmacokinetics (PK) of SHR7390.The design to assess food-effect is a randomized, balanced, 2-treatment(fed vs. fasted), separated by an adequate wash-out period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SHR7390 | Experimental | Drug: SHR739060 subjects with advanced solid tumors were received single and then multiple oral doses of SHR7390(2 cycles,each cycle 28days). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- The study is open to all males and females who meet the following inclusion criteria at screening and baseline to participate in the study.
- 18-70 years of age, both women and men;
- invalid the standard treatment or non standard and effective treatment in patients with advanced solid tumors diagnosed by pathology;
- the Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS) of 0-1;
- the expected lifetime ≥ 3 months;
Key exclusion criteria (18 listed)
- Subjects who meet any of the criteria listed below will not be eligible for participation in this study. A patient will not be eligible for study participation if:
- Previous treatment with other protein kinase MEK inhibitors;
- Use of other investigational anti-cancer drugs or the termination of the investigational drugs within the last four weeks;
- Currently or possibly receiving other cancer therapy during the study period;
- Presence of a factor that influences the oral drug (such as inability to swallow) or presence of active gastrointestinal disease or other conditions that will interfere significantly with the absorption, distribution, metabolism, or excretion of drug;
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 |
|---|---|---|
| SHR7390Also: MEK inhibitorSHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg and 0.5 mg. Multiple tablets of SHR7390 will be administered daily to achieve targeted doses of SHR7390: 0.25 mg-4 mg. Tablets will be orally administered with 240 ml water, once daily, 2 hours after a meal. | Drug | SHR7390 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Day 1 to 28 ( Cycle 1)
to assess safety and tolerability of SHR7390 with a maximum tolerated dose (MTD) of SHR7390 in patients with advanced solid tumors
20 secondary outcomes
The measurement of maximum plasma concentration (Cmax)
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of the area under the plasma concentration-time versus time curve(AUC)
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of elimination half life (T1/2)
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of time of maximum plasma concentration (Tmax)
Time frame: Up to 2 cycles(each cycle 28 days)
The Measurement of mean retention time (MRT)
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of apparent volume of distribution (Vd)
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of clearance (Cl)
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of linear Relationship
Time frame: Up to 2 cycles(each cycle 28 days)
The measurement of drug accumulation ratio
Time frame: Up to 2 cycles(each cycle 28 days)
The comparison of maximum plasma concentration (Cmax) in the fed and fasted states
Time frame: 2 weeks
The comparison of the area under the plasma concentration-time versus time curve(AUC) in the fed and fasted states
Time frame: 2 weeks
The comparison of elimination half life(T1/2) in the fed and fasted states
Time frame: 2 weeks
The comparison of time of maximum concentration (Tmax) in the fed and fasted states
Time frame: 2 weeks
The comparison of mean retention time (MRT) in the fed and fasted states
Time frame: 2 weeks
The comparison of apparent volume of distribution (Vd）in the fed and fasted states
Time frame: 2 weeks
The comparison of clearance (Cl) in the fed and fasted states
Time frame: 2 weeks
The comparison of AUC 0-24h in the fed and fasted states
Time frame: 2 weeks
The imaging data of the subjects will be evaluated at the ends of cycle 1 and cycle 2 by RECIST1.1 evaluation criteria separately.
Time frame: 2 cycles(each cycle 28 days)
Response rate objective (ORR) will be evaluated at the different dose levels
Time frame: 2 cycles(each cycle 28 days)
Disease control rate (DCR) will be evaluated at the different dose levels
Time frame: 2 cycles(each cycle 28 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2019.
- 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.
RuiHua Xu, MD, PhD principal investigator
The Cancer Center,Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SHR7390 in people with Solid Tumor, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
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 18 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: status not confirmed, as of the sponsor's last update on 15 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact RuiHua Xu, MD, PhD (86-20-8734-3008, xurh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Day 1 to 28 ( Cycle 1)). 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 15 Jan 2019.