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An Open Study Assessing the Safety and Tolerability of U3-1784

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ClinicalTrials.gov Identifier: NCT02690350
Recruitment Status : Terminated (Program discontinued for business reasons (not safety).)
First Posted : February 24, 2016
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE February 12, 2016
First Posted Date  ICMJE February 24, 2016
Last Update Posted Date May 16, 2018
Actual Study Start Date  ICMJE February 29, 2016
Actual Primary Completion Date February 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 18, 2016)
  • number and severity of adverse events [ Time Frame: at week 4 ]
    To evaluate the safety and tolerability of U3-1784 in patients with advanced solid tumours after 4 weeks.
  • number of participants with treatment-related adverse events [ Time Frame: at week 4 ]
    number of participants with treatment-related adverse events as assessed by CTCAE v 4.0 at 4 weeks, to determine maximum tolerated dose (MTD).
Change History Complete list of historical versions of study NCT02690350 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2016)
  • Tmax time of maximum concentration [ Time Frame: at week 4 ]
    assess the pharmacokinetics of U3-1784 in patients
  • Cmax maximum concentration [ Time Frame: at week 4 ]
    assess the pharmacokinetics of U3-1784 in patients
  • AUC area under the concentration curve [ Time Frame: at week 4 ]
    assess the pharmacokinetics of U3-1784 in patients
  • level of antidrug antibodies (ADA) [ Time Frame: at week 8 ]
    To assess emergence of antidrug antibodies (ADAs) for the duration of treatment based (at least 8 weeks).
  • level of alpha-fetoprotein [AFP] [ Time Frame: at week 8 ]
    To evaluate biomarker that is related to the pharmacodynamics of drug action, or to the response to U3-1784 (alpha-fetoprotein [AFP]) After 8 weeks from start of treatment.
  • level of bile acids (BA) [ Time Frame: at week 8 ]
    To evaluate biomarker that is related to the pharmacodynamics of drug action, or to the response to U3-1784 (bile acids [BAs]) After 8 weeks from start of treatment.
  • level of aspartate aminotransferase [ Time Frame: at week 8 ]
    To evaluate biomarker that is related to the pharmacodynamics of drug action, or to the response to U3-1784 (aspartate aminotransferase) After 8 weeks from start of treatment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open Study Assessing the Safety and Tolerability of U3-1784
Official Title  ICMJE A Phase 1, Open-label, Two-part, Safety and Tolerability Study of U3-1784 in Patients With Advanced Solid Tumours
Brief 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Single arm, three cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Hepatocellular Cancer (HCC)
Intervention  ICMJE Drug: U3-1784
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
Other Name: Experimental product
Study Arms  ICMJE
  • Experimental: Cohort 1 U3-1784 2.5 mg/kg
    U3-1784 (2.5 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated
    Intervention: Drug: U3-1784
  • Experimental: Cohort 2 U3-1784 3.75 mg/kg
    U3-1784 (3.75 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated
    Intervention: Drug: U3-1784
  • Experimental: Cohort 3 U3-1784 5.6 mg/kg
    U3-1784 (5.6 mg/kg) by intravenous infusion, along with colestyramine or equivalent if clinically indicated
    Intervention: Drug: U3-1784
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 6, 2017)
10
Original Estimated Enrollment  ICMJE
 (submitted: February 18, 2016)
63
Actual Study Completion Date  ICMJE February 28, 2017
Actual Primary Completion Date February 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • 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

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02690350
Other Study ID Numbers  ICMJE U31784-A-E101
2015-002670-20 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alberto Martinez, PhD Daiichi Sankyo UK Ltd.
PRS Account Daiichi Sankyo, Inc.
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP