Gastric CancerPhase 1NCT02252913
A Study of Safety and Pharmacokinetics of Volitinib With Docetaxel in Patients With Advanced Gastric Cancer
A Phase 1 study testing Volitinib and Docetaxel in people with Gastric Cancer, run by Hutchison Medipharma Limited at 1 site in China.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of volitinib in combination with docetaxel in patients with locally advanced or metastatic gastric cancer and to determine the Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of volitinib in combination with docetaxel. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Cancer
- What is being tested?
- Volitinib and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- Sep 2014to Dec 2015
- 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
- Signed Informed Consent Form
- Age ≥18 years
- Histologically or cytologically documented, locally advanced, or metastatic gastric cancer patients who have failed the first line platinum and fluoropyrimidine based treatment. Adjuvant or neoadjuvant chemotherapy will be considered as first line treatment for advanced disease if disease progression occurred during or within 6 months of treatment.
- In the dose expansion stage, patients must have positive cMet test results by a central laboratory
- Absolute neutrophil count (ANC) ≥ 1.5x109/L, hemoglobin ≥ 9 g/dL and platelet count ≥ 100x109/L
- Total bilirubin ≤ULN; SGOT (AST), SGPT (ALT), ≤ 1.5xULN; alkaline phosphatase (ALP) ≤ 2.5xULN
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- Serum creatinine <1.5xULN or creatinine clearance ≥50mls/minute; confirmation of creatinine clearance is only required when creatinine is >1.5 ULN
- International normalized ratio (INR) ≤1.5xthe ULN or activated partial thromboplastin time (aPTT) ≤1.5xthe ULN. The INR applies only to patients who do not receive therapeutic anti-coagulation.
- Evaluable disease at dose escalation stage and measurable disease at dose expansion stage per RECIST v1.1
- ECOG performance status of 0, or 1
- Expected survival > 3 months
- Male or female patients of child-producing potential must agree to double barrier contraception, condoms, intrauterine device (IUD), or contraceptives or other effective avoidance of pregnancy measures during the study and for 90 days after the last dose of treatment
- Female patients of child-producing potential must have a negative pregnancy test prior to start of dosing or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.
- Patients with known tumor thrombus or deep vein thrombosis (DVT) are eligible if stable on low molecular weight heparin (LMWH) for ≥4 weeks.
Who cannot join
- Prior taxane or cMet inhibitor therapy for advanced disease. Prior taxane containing regimen as adjuvant or neoadjuvant therapy can be allowed provided relapse occurred at least 6 months after therapy
- Co-existing malignancy or malignancies diagnosed within the last 3 years other than Gastric with the exception of skin basal cell carcinoma or cervical cancer in situ at dose expansion stage.
- Any anti-cancer therapy, including, but not limited to chemotherapy, hormonal therapy, target therapy, immunotherapy, biologic therapy, radiotherapy, or herbal therapy within 3 weeks prior to initiation of study treatment with the following exceptions:
- Hormone-replacement therapy or oral contraceptives
- Palliative radiation to bone metastases 2 weeks prior to Day 1
- Strong inducers or inhibitors of CYP3A4 or strong inhibitors of CYP1A2 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort). See appendix 5
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- Adverse events from prior anti-cancer therapy that have not resolved to CTC AE Grade 1, except for alopecia
- Clinically significant active infection
- Known clinically significant history of liver disease, including viral or other hepatitis , current alcohol abuse, or cirrhosis
- Known human immunodeficiency virus（HIV）infection
- Pregnant or lactating women
- NYHA Class II or greater congestive heart failure
- History of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months prior to study entry , or cardiac ventricular arrhythmias requiring medication
- Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin (LMWH) is allowed
- Brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation, or previously treated CNS metastases or spinal cord compression without evidence of stable disease (clinically stable imaging) for ≥ 14 days. Current leptomeningeal metastases.
- Inability to take oral medication, prior surgical procedures (except prior total or partial gastrectomy) or serious gastrointestinal disorders such as dysphagia and active peptic ulcer disease that may affect drug absorption in the opinion of the investigator
- Inability to comply with study and follow-up procedures
- Known hypersensitivity to taxanes, and/or any components of Volitinib tablet or docetaxel formulation components (eg, polysorbate 80).
- More than grade 2 peripheral neuropathy or grade 2 peripheral neuropathy with pain.
- Any other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory finding that, in the investigator's opinion, may give reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or may render the patient at high risk from treatment complications.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase Ib, Open-label Study of Safety and Pharmacokinetics of Volitinib in Combination With Docetaxel in Patients With Advanced Gastric Cancer
The purpose of this study is to evaluate the safety and tolerability of volitinib in combination with docetaxel in patients with locally advanced or metastatic gastric cancer and to determine the Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of volitinib in combination with docetaxel.
Read the detailed description
This is a phase Ib, open-label study.
There are two stages to this study: a dose-escalation stage and a dose-expansion stage. Approximately 40-50 patients will be enrolled in this two-stage study, about 12-18 patients in the dose-escalation stage and approximately 30 patients in the dose-expansion stage.
Dose escalation stage
Gastric cancer patients who failed the first line therapy (no matter the cMet status) who meet the eligibility criteria will be enrolled into this stage.
Cohort 1: Volitinib 600mg QD + docetaxel 75mg/m2 Cohort 2: Volitinib 800mg QD+ docetaxel 75mg/m2 The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and MTD or RP2D determination. Each treatment cycle will be composed of 3 weeks or 21 days. Dose escalation and entry of the next cohort will occur only after acceptable tolerance has been demonstrated throughout the entire Cycle1.
Dose expansion Stage
Additional patients will be enrolled at the MTD or RP2D to further refine the safety, tolerability, PK, and efficacy at this dose. Patients will be limited to the metastatic / locally advanced gastric cancer patients who failed the first therapy and with positive cMet test results. Patients will be divided into two treatment groups according their c-Met test results:
Group A: FISH + , IHC -/+(about 15 patients) Group B: IHC+ and FISH- (about 15 patients)
- Conditions
- Gastric Cancer
- Being tested
- Volitinib, Docetaxel
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolitinibDrug
Also called HMPL-504
oral administration
DocetaxelDrug
Also called Taxotere
intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| Volitinib+docetaxel | Experimental | Dose escalation stage: oral administration, Volitinib 600mg/800 QD + docetaxel 75mg/m2.
If the dose of docetaxel 75mg/m2 is not tolerable, docetaxel dose will be reduced to 60mg/m2 while keep volitinib at 600mg QD as the initial dose. Volitinib dose escalation will be re-started and end at the dose of 800mg QD.
Dose expansion Stage:Volitinib with docetaxel. Use the prefer dose from escalation stage Receives: Drug: Volitinib; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and tolerability
- Incidence and nature of DLTs
- Incidence and severity of AE/SAEs
Measured: 21days
Secondary outcomes (1)
PK parameters
- Area Under Curve (AUC)
- Maximum plasma concentration (Cmax)
- Clearance (CL/F)
- Volume of distribution (Vd/F)
- Other parameters, such as accumulation ratio, elimination half-life
Measured: 22 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Jin Li, Prof., Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02252913
- Sponsor's protocol ID
- 2014-504-00CH1
- Status last verified
- Apr 2016
- First submitted
- 16 Sep 2014
- Last updated
- 8 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-label Study of Safety and Pharmacokinetics of Volitinib in Combination With Docetaxel in Patients With Advanced Gastric Cancer
- ClinicalTrials.gov ID
- NCT02252913
- Acronym / sponsor ID
- 2014-504-00CH1
- Conditions
- Gastric Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Study start
- Sep 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 30 Sep 2014 (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.
The purpose of this study is to evaluate the safety and tolerability of volitinib in combination with docetaxel in patients with locally advanced or metastatic gastric cancer and to determine the Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of volitinib in combination with docetaxel.
Detailed description
This is a phase Ib, open-label study.
There are two stages to this study: a dose-escalation stage and a dose-expansion stage. Approximately 40-50 patients will be enrolled in this two-stage study, about 12-18 patients in the dose-escalation stage and approximately 30 patients in the dose-expansion stage.
Dose escalation stage
Gastric cancer patients who failed the first line therapy (no matter the cMet status) who meet the eligibility criteria will be enrolled into this stage.
Cohort 1: Volitinib 600mg QD + docetaxel 75mg/m2 Cohort 2: Volitinib 800mg QD+ docetaxel 75mg/m2 The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and MTD or RP2D determination. Each treatment cycle will be composed of 3 weeks or 21 days. Dose escalation and entry of the next cohort will occur only after acceptable tolerance has been demonstrated throughout the entire Cycle1.
Dose expansion Stage
Additional patients will be enrolled at the MTD or RP2D to further refine the safety, tolerability, PK, and efficacy at this dose. Patients will be limited to the metastatic / locally advanced gastric cancer patients who failed the first therapy and with positive cMet test results. Patients will be divided into two treatment groups according their c-Met test results:
Group A: FISH + , IHC -/+(about 15 patients) Group B: IHC+ and FISH- (about 15 patients)
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Volitinib+docetaxel | Experimental | Drug: Volitinib, Drug: DocetaxelDose escalation stage: oral administration, Volitinib 600mg/800 QD + docetaxel 75mg/m2. If the dose of docetaxel 75mg/m2 is not tolerable, docetaxel dose will be reduced to 60mg/m2 while keep volitinib at 600mg QD as the initial dose. Volitinib dose escalation will be re-started and end at the dose of 800mg QD. Dose expansion Stage:Volitinib with docetaxel. Use the prefer dose from escalation stage |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Signed Informed Consent Form
- Age ≥18 years
- Histologically or cytologically documented, locally advanced, or metastatic gastric cancer patients who have failed the first line platinum and fluoropyrimidine based treatment. Adjuvant or neoadjuvant chemotherapy will be considered as first line treatment for advanced disease if disease progression occurred during or within 6 months of treatment.
- In the dose expansion stage, patients must have positive cMet test results by a central laboratory
- Absolute neutrophil count (ANC) ≥ 1.5x109/L, hemoglobin ≥ 9 g/dL and platelet count ≥ 100x109/L
Key exclusion criteria (20 listed)
- Prior taxane or cMet inhibitor therapy for advanced disease. Prior taxane containing regimen as adjuvant or neoadjuvant therapy can be allowed provided relapse occurred at least 6 months after therapy
- Co-existing malignancy or malignancies diagnosed within the last 3 years other than Gastric with the exception of skin basal cell carcinoma or cervical cancer in situ at dose expansion stage.
- Any anti-cancer therapy, including, but not limited to chemotherapy, hormonal therapy, target therapy, immunotherapy, biologic therapy, radiotherapy, or herbal therapy within 3 weeks prior to initiation of study treatment with the following exceptions:
- Strong inducers or inhibitors of CYP3A4 or strong inhibitors of CYP1A2 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort). See appendix 5
- Adverse events from prior anti-cancer therapy that have not resolved to CTC AE Grade 1, except for alopecia
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 |
|---|---|---|
| VolitinibAlso: HMPL-504oral administration | Drug | Volitinib+docetaxel |
| DocetaxelAlso: Taxotereintravenous injection | Drug | Volitinib+docetaxel |
Primary outcome
safety and tolerability
Time frame: 21days
* Incidence and nature of DLTs * Incidence and severity of AE/SAEs
1 secondary outcome
PK parameters
Time frame: 22 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 8 Apr 2016.
- 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. This study is not recruiting at the moment.
Jin Li, Prof. principal investigator
Fudan 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 Volitinib and Docetaxel in people with Gastric Cancer, run by Hutchison Medipharma Limited 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 17 inclusion and 20 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 8 Apr 2016. 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?
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?
safety and tolerability (time frame: 21days). 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 8 Apr 2016; AzTrials last refreshed its copy on 8 Nov 2026.