Advanced Solid TumorsPhase 1NCT02690350
An Open Study Assessing the Safety and Tolerability of U3-1784
A Phase 1 study testing U3-1784 in people with Advanced Solid Tumors and Hepatocellular Cancer (HCC), run by Daiichi Sankyo at 4 sites in United Kingdom.
Trial summary
The main objectives of the trial are: To evaluate the safety and tolerability of U3-1784 in patients with advanced solid tumours To determine the maximum tolerated dose (MTD) and or establish the safety and tolerability of the maximum administered dose (MAD) of U3-1784 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Hepatocellular Cancer (HCC)
- What is being tested?
- U3-1784
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 29 Feb 2016to 28 Feb 2017
- 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
- Part 1: Patients with histologically or cytologically confirmed advanced solid tumours refractory to, intolerant of, or not eligible for standard treatment, or who decline standard therapy, or for whom no therapy with curative intent is available
- Part 2: Patients with histologically or cytologically confirmed HCC refractory to, intolerant of, or not eligible for standard treatment, or who decline standard therapy, or for whom no therapy with curative intent is available. If emerging Part 1 data suggest that a particular tumour type or specific tumour histology might be responsive to treatment, then patients with this tumour type or histology will also be included in Part 2 of the study.
- Male or female patients, 18 years of age or older.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment.
- Males and females of childbearing potential are permitted in the study so long as they consent to avoid getting their partner pregnant or becoming pregnant, respectively, by using a highly effective contraception method, as described below, throughout the study and for up to 90 days after completion. Highly effective methods of contraception include: hormonal methods associated with inhibition of ovulation, intrauterine device; surgical sterilization (including partner's vasectomy) or sexual abstinence, if this is the preferred and usual lifestyle of the subject. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year Eastern Cooperative Oncology Group performance status ≤ 1.
- Life expectancy of greater than 3 months.
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- Ability to understand and the willingness to sign a written informed consent form.
- Measurable or evaluable disease as defined by RECIST Version 1.1 in Part 1 of the study (patients included in Part 2 will be required to have measurable disease). The measurable lesion in HCC patients should not be one that has been previously treated by loco-regional therapies (e.g. TACE, RFA) unless this lesion has progressed and there is evidence of new, measurable, enhancement on dynamic imaging.
- Patient has 1 of the following available for pharmacodynamic analyses:
- Archived diagnostic or freshly obtained formalin-fixed paraffin embedded or frozen tumour tissue
- Tumour tissue biopsy collected prior to study drug administration
- Patient has adequate bone marrow, renal, and hepatic function as follows:
- Haemoglobin: ≥ 90 g/L
- Absolute Neutrophil Count: ≥ 1.5 × 109/L
- Platelets: ≥ 100 × 109/L (Part 1); ≥ 75 × 109/L (Part 2)
- Total Bilirubin: ≤ 1.5 × upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT): ≤ 2.5 × institutional ULN
- Prothrombin Time (PT)/International Normalised Ratio (INR): ≤ 1.5 (patients on anticoagulants will have PT and INR as determined by the Investigator)
- Serum creatinine: ≤ 1.5 × ULN or Creatinine Clearance (calculated from serum creatinine using Cockcroft-Gault formula) ≥ 60 mL/min for patients with creatinine levels above institutional normal
Who cannot join
- Patient has received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy or loco-regional therapy within a period of 21 days prior to Study Day 1 (6 weeks for nitrosureas or mitomycin C). Prior and concurrent use of hormone replacement therapy, use of gonadotropin-releasing hormone modulators for prostate cancer, and use of somatostatin analogues for neuroendocrine tumours are permitted.
- Patient has unresolved clinically significant toxicities from prior anticancer therapy, defined as any National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03; Grade 2 or higher, apart from alopecia.
- Patients with heart failure (New York Heart Association > Class II) within 6 months prior to study entry; symptomatic coronary artery disease; clinically significant cardiac arrhythmia defined as ≥ Grade 3 to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03; uncontrolled hypertension, myocardial infarction occurring within 6 months prior to study entry.
- Patient has active clinically serious infection defined as ≥ Grade 3 to NCI CTCAE, Version 4.03.
- Patients with clinically significant pericardial effusions, pleural effusions or ascites.
- Patient has had another active malignancy within the past 3 years except for nonmelanoma carcinoma of the skin, cervical carcinoma in situ, and superficial bladder tumours.
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- Patient has had major surgery within 4 weeks before enrolment.
- Patient has known hypersensitivity to colestyramine (or any of its excipients) or history of hypersensitivity/allergic reactions attributed to other monoclonal antibodies
- Patients with complete biliary obstruction
- Lactating women
- Additional exclusion criteria for HCC patients included in Part 1 and Part 2:
- Concomitant interferon therapy or therapies for active Hepatitis C Virus infection.
- Patient has history of liver transplant.
- Patient has Child-Pugh B-C cirrhotic status based on clinical findings and laboratory results during screening period.
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Study site
Glasgow, Lanarkshire, G12 0YN
Guy's Hospital
London
The Christie NHS Foundation Trust
Manchester
The Royal Marsden Hospital
Sutton, Surrey
About this study
Official title: A Phase 1, Open-label, Two-part, Safety and Tolerability Study of U3-1784 in Patients With Advanced Solid Tumours
The main objectives of the trial are:
- To evaluate the safety and tolerability of U3-1784 in patients with advanced solid tumours
- To determine the maximum tolerated dose (MTD) and or establish the safety and tolerability of the maximum administered dose (MAD) of U3-1784
- Conditions
- Advanced Solid Tumors, Hepatocellular Cancer (HCC)
- Being tested
- U3-1784
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
U3-1784Drug
Also called Experimental product
Solution for solution in 5% dextrose for infusion, intravenously administered every 2 weeks (q2w) as a 250 mL IV, along with colestyramine or equivalent if clinically indicated
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 U3-1784 2.5 mg/kg | Experimental | U3-1784 (2.5 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated Receives: Drug: U3-1784 |
| Cohort 2 U3-1784 3.75 mg/kg | Experimental | U3-1784 (3.75 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated Receives: Drug: U3-1784 |
| Cohort 3 U3-1784 5.6 mg/kg | Experimental | U3-1784 (5.6 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated Receives: Drug: U3-1784 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients with Adverse Events
Treatment emergent adverse events (TEAEs) are systematically collected - clinically significant changes in laboratory values are recorded as TEAEs in system organ class: Investigations
Measured: within 1 year
Number of Patients with Dose-Limiting Toxicities (DLTs)
Measured: from start of treatment until trial termination (within 2 months)
Secondary outcomes (3)
Maximum Concentration (Cmax)
Measured: within 2 months
Time to Cmax (Tmax)
Measured: within 2 months
Area Under the Curve to the Last Quantifiable Measure (AUClast)[
Measured: within 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study start29 Feb 2016
- Primary completion28 Feb 2017
- Study completion28 Feb 2017
Why it stopped: Program discontinued for business reasons (not safety).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Single arm, three cohorts
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alberto Martinez, PhD, Study director, Daiichi Sankyo UK Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02690350
- Sponsor's protocol ID
- U31784-A-E101
- Other IDs
- 2015-002670-20, 2015
- Status last verified
- May 2018
- First submitted
- 12 Feb 2016
- Last updated
- 16 May 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Two-part, Safety and Tolerability Study of U3-1784 in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT02690350
- Acronym / sponsor ID
- U31784-A-E101
- Conditions
- Advanced Solid Tumors, Hepatocellular Cancer (HCC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Program discontinued for business reasons (not safety).
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 29 Feb 2016 (actual)
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 24 Feb 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.
The main objectives of the trial are:
- To evaluate the safety and tolerability of U3-1784 in patients with advanced solid tumours
- To determine the maximum tolerated dose (MTD) and or establish the safety and tolerability of the maximum administered dose (MAD) of U3-1784
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Single arm, three cohorts
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 U3-1784 2.5 mg/kg | Experimental | Drug: U3-1784U3-1784 (2.5 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated |
| Cohort 2 U3-1784 3.75 mg/kg | Experimental | Drug: U3-1784U3-1784 (3.75 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated |
| Cohort 3 U3-1784 5.6 mg/kg | Experimental | Drug: U3-1784U3-1784 (5.6 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Part 1: Patients with histologically or cytologically confirmed advanced solid tumours refractory to, intolerant of, or not eligible for standard treatment, or who decline standard therapy, or for whom no therapy with curative intent is available
- Part 2: Patients with histologically or cytologically confirmed HCC refractory to, intolerant of, or not eligible for standard treatment, or who decline standard therapy, or for whom no therapy with curative intent is available. If emerging Part 1 data suggest that a particular tumour type or specific tumour histology might be responsive to treatment, then patients with this tumour type or histology will also be included in Part 2 of the study.
- Male or female patients, 18 years of age or older.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment.
- Males and females of childbearing potential are permitted in the study so long as they consent to avoid getting their partner pregnant or becoming pregnant, respectively, by using a highly effective contraception method, as described below, throughout the study and for up to 90 days after completion. Highly effective methods of contraception include: hormonal methods associated with inhibition of ovulation, intrauterine device; surgical sterilization (including partner's vasectomy) or sexual abstinence, if this is the preferred and usual lifestyle of the subject. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year Eastern Cooperative Oncology Group performance status ≤ 1.
Key exclusion criteria (14 listed)
- Patient has received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy or loco-regional therapy within a period of 21 days prior to Study Day 1 (6 weeks for nitrosureas or mitomycin C). Prior and concurrent use of hormone replacement therapy, use of gonadotropin-releasing hormone modulators for prostate cancer, and use of somatostatin analogues for neuroendocrine tumours are permitted.
- Patient has unresolved clinically significant toxicities from prior anticancer therapy, defined as any National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03; Grade 2 or higher, apart from alopecia.
- Patients with heart failure (New York Heart Association > Class II) within 6 months prior to study entry; symptomatic coronary artery disease; clinically significant cardiac arrhythmia defined as ≥ Grade 3 to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03; uncontrolled hypertension, myocardial infarction occurring within 6 months prior to study entry.
- Patient has active clinically serious infection defined as ≥ Grade 3 to NCI CTCAE, Version 4.03.
- Patients with clinically significant pericardial effusions, pleural effusions or ascites.
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 |
|---|---|---|
| U3-1784Also: Experimental productSolution for solution in 5% dextrose for infusion, intravenously administered every 2 weeks (q2w) as a 250 mL IV, along with colestyramine or equivalent if clinically indicated | Drug | Cohort 1 U3-1784 2.5 mg/kg, Cohort 2 U3-1784 3.75 mg/kg, Cohort 3 U3-1784 5.6 mg/kg |
Primary outcome
Number of Patients with Adverse Events
Time frame: within 1 year
Treatment emergent adverse events (TEAEs) are systematically collected - clinically significant changes in laboratory values are recorded as TEAEs in system organ class: Investigations
Number of Patients with Dose-Limiting Toxicities (DLTs)
Time frame: from start of treatment until trial termination (within 2 months)
3 secondary outcomes
Maximum Concentration (Cmax)
Time frame: within 2 months
Time to Cmax (Tmax)
Time frame: within 2 months
Area Under the Curve to the Last Quantifiable Measure (AUClast)[
Time frame: within 2 months
Results and safety
The study was stopped early (reason given: Program discontinued for business reasons (not safety).). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2018.
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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.
Alberto Martinez, PhD study director
Daiichi Sankyo UK Ltd.
4 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 U3-1784 in people with Advanced Solid Tumors and Hepatocellular Cancer (HCC), run by Daiichi Sankyo at 4 sites in United Kingdom.
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 19 inclusion and 14 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: stopped early, as of the sponsor's last update on 16 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom. 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 was stopped early (reason given: Program discontinued for business reasons (not safety).). Results are not available in the source record.
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 Patients with Adverse Events (time frame: within 1 year). 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 16 May 2018.