A Phase 1 Study of Dexanabinol in Patients With Advanced... | NCT01489826

NCT01489826

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dexanabinol 2 mg/kg	Experimental	Dexanabinol 2 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)	Drug: Dexanabinol Other: Cremophor
Dexanabinol 3 mg/kg	Experimental	Dexanabinol 3 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)	Drug: Dexanabinol Other: Cremophor
Dexanabinol 6 mg/kg	Experimental	Dexanabinol 6 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)	Drug: Dexanabinol Other: Cremophor
Dexanabinol 12 mg/kg	Experimental	Dexanabinol 12 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)	Drug: Dexanabinol Other: Cremophor
Dexanabinol 15 mg/kg	Experimental	Dexanabinol 15 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)	Drug: Dexanabinol Other: Cremophor

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dexanabinol	Drug	Patients will (initially) be given a slow intravenous (i.v.) infusion of Dexanabinol over 3 hours on Days 1, 8 and 15 of a three weekly (21 day) cycle.	Dexanabinol 12 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients Experiencing Dose Limiting Toxicity (DLT)	Patients will be sequentially assigned to increasing doses of Dexanabinol, to establish the maximum tolerated dose (MTD) (highest dose it is safe to give patients) or alternatively the maximum administered dose (MAD). 3 patients will be enrolled to a cohort to assess each dose level. Dose escalation to a cohort of 3 new patients will occur when all patients in the previous cohort have completed the first cycle i.e. the first 3 doses followed by observation through to Day 22, and no DLT has occurred. Upon occurrence of the first DLT within a cohort, an additional 3 patients were to be added to that cohort. For a six patient cohort, all 6 patients were to have completed their first dexanabinol treatment cycle with no more than 1 DLT before dose escalation to the next cohort. If 2 or more DLTs occur in a cohort, the next lower dose level will be declared the MTD. DLTs will be graded for severity based on the National Cancer Institute (NCI) Common Terminology Criteria version 4.03.	Each patient will be followed for 22 days

Secondary Outcomes

Measure	Description	Time Frame
Area Under Curve (AUC) of Dexanabinol on Cycle 1 Day 1	Geometric mean AUC of Dexanabinol (0-infinity) on Cycle 1 Day 1.	Cycle 1- Day 1: pre-dose (0h); 1, 2, 3 h post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24 h post-end infusion.
Maximum Concentration (Cmax) of Dexanabinol Cycle 1 Day 1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult patients defined by age ≥18 years.
Patients with histologically or cytologically confirmed solid tumours that are advanced, metastatic and or progressive, for whom there is no effective standard therapy available.
Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2.
Any acute or chronic adverse effects of prior chemotherapy or radiotherapy have resolved to < Grade 2 as determined by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, with the exception of alopecia.
Evaluable disease, either measurable on imaging, or with informative tumour marker(s), as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Eisenhauer, et al. 2009).
Laboratory values at Screening:
- Absolute neutrophil count ≥1.5 x 109/L;
- Platelets ≥100 x 109/L;
- Total bilirubin <1.5 times the upper limit of normal;
- Aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal;
- Alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal;
- Estimated glomerular filtration rate (GFR) of >50 mL/min (based on the Wright formula (Wright, et al. 2001); and
- Negative human chorionic gonadotropin (hCG) test in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry). Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control (e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study and for 1 month after final administration of Dexanabinol, or the patient must be surgically sterile (with documentation in the patient's medical records).
If there is a history of treated brain metastases, these must have been clinically stable for ≥4 weeks prior to enrollment.
Have a life expectancy of >3 months.
Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.
Be willing and able to comply with the study protocol procedures.

Exclusion Criteria:

Patient is pregnant or breast feeding.
History of clinically significant cardiac condition, including ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months of Cycle 1, Day 1.
Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control.
Major surgery within 6 weeks prior to Cycle 1, Day 1.
Known human immunodeficiency virus positivity.
Active hepatitis B or C or other active liver disease (other than malignancy).
Use of any investigational agents within 4 weeks of Cycle 1, Day 1.
Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
History of significant chronic or recurrent infections requiring treatment or any uncontrolled intercurrent illness that would jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Ruth Plummer, MD	Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK	Principal Investigator
Alan Anthoney, MD	Leeds Cancer Centre at St. James's University Hospital	Principal Investigator
Jeff Evans, MD	The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Leeds Cancer Centre at St. James's University Hospital		Leeds	England	LS9 7TF	United Kingdom
Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	Dexanabinol 2 mg/kg	Dexanabinol 2 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG001	Dexanabinol 3 mg/kg	Dexanabinol 3 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG002	Dexanabinol 6 mg/kg	Dexanabinol 6 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG003	Dexanabinol 12 mg/kg	Dexanabinol 12 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG004	Dexanabinol 15 mg/kg	Dexanabinol 15 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG005	Dexanabinol 22 mg/kg	Dexanabinol 22 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG006	Dexanabinol 30 mg/kg	Dexanabinol 30 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG007	Dexanabinol 36 mg/kg	Dexanabinol 36 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)
FG008	Dexanabinol Expansion Phase	Dexanabinol 30 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0023 subjects FG0037 subjects FG0043 subjects FG0053 subjects FG0069 subjects FG0073 subjects FG0086 subjects
COMPLETED		FG0003 subjects FG0013 subjects FG0023 subjects FG0037 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Dexanabinol Dose Escalation - Cohort 1	Open label, dose escalation phase to assess tolerability and pharmacokinetics of dexanabinol in patients with advanced tumours
BG001	Dexanabinol Dose Escalation - Cohort 2

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Number of Patients Experiencing Dose Limiting Toxicity (DLT)	Patients will be sequentially assigned to increasing doses of Dexanabinol, to establish the maximum tolerated dose (MTD) (highest dose it is safe to give patients) or alternatively the maximum administered dose (MAD). 3 patients will be enrolled to a cohort to assess each dose level. Dose escalation to a cohort of 3 new patients will occur when all patients in the previous cohort have completed the first cycle i.e. the first 3 doses followed by observation through to Day 22, and no DLT has occurred. Upon occurrence of the first DLT within a cohort, an additional 3 patients were to be added to that cohort. For a six patient cohort, all 6 patients were to have completed their first dexanabinol treatment cycle with no more than 1 DLT before dose escalation to the next cohort. If 2 or more DLTs occur in a cohort, the next lower dose level will be declared the MTD. DLTs will be graded for severity based on the National Cancer Institute (NCI) Common Terminology Criteria version 4.03.	Patients will be sequentially assigned to increasing doses of Dexanabinol, to establish the MTD (highest dose it is safe to give patients) or alternatively the Maximum Administered Dose(MAD). DLT evaluation in 3 to 6 patients at end of 1 treatment cycle	Posted		Number		Number of patients with DLT		Each patient will be followed for 22 days

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dexanabinol 2 mg/kg	Dexanabinol 2 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (16.1)

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Clinical Operations Manager	e-Therapeutics plc	+44 1993 880000		contact@etherapeutics.co.uk

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009369	Neoplasms

Intervention Browse Module

ID	Term
C062018	HU 211
C022131	cremophor

Masking Info

Dexanabinol 15 mg/kg

Dexanabinol 22 mg/kg

Dexanabinol 30 mg/kg

Dexanabinol 36 mg/kg

Dexanabinol Expansion Phase

Open label, dose escalation phase to assess tolerability and pharmacokinetics of dexanabinol in patients with advanced tumours

EG0000 events0 affected3 at risk

EG0010 events0 affected3 at risk

EG0020 events0 affected3 at risk

EG0031 events1 affected7 at risk

EG0041 events1 affected3 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected9 at risk

EG0070 events0 affected3 at risk

EG0081 events1 affected6 at risk

EG0012 events2 affected3 at risk

EG0020 events0 affected3 at risk

EG0033 events2 affected7 at risk

EG00412 events2 affected3 at risk

EG0051 events1 affected3 at risk

EG0067 events2 affected9 at risk

EG0075 events3 affected3 at risk

EG0081 events1 affected6 at risk

Upper inter-quartile range could not be calculated due to censored value.

OG00343.0(36.0 to 51.0)

OG004176.0(86.0 to 176.0)

OG005293.0(293.0 to 293.0)

OG00640.5(36.0 to 66.0)

OG007NA(43.0 to NA)Median could not be calculated as there were only two values. Upper inter-quartile range could not be calculated due to censored value.

OG00837.0(36.0 to 49.0)