Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
2009-001
Study information
Scientific title
A phase I, open-label, dose-finding study to evaluate the safety and pharmacokinetics of ONX 0801, a novel alpha-folate receptor-mediated thymidylate synthase inhibitor, in patients with advanced solid tumours
Acronym
Study hypothesis
Is ONX 0801 tolerable and safe in cancer patients and can a dose be identified which inhibits tumour cell growth in future clinical studies?
Ethics approval(s)
Royal Marsden Hospital Ethics Committee and the Hammersmith Ethics Committee – submission pending, planned for June 2009
Study design
Phase I open-label dose-finding study
Primary study design
Interventional
Secondary study design
Non randomised study
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details provided in the interventions section to request a patient information sheet
Condition
Advanced solid tumours
Intervention
Cohorts of 3 to 6 patients will receive ONX 0801 at escalating doses until a maximum tolerated dose (MTD) is determined. Each patient will receive a 3-hour intravenous (IV) infusion of ONX 0801 weekly (i.e., on days 1, 8, and 15) of repeated 21-day treatment cycles.
Contact details for patient information material:
Udai Banerji, MD, MRCP, PhD
Clinical Senior Lecturer
Section of Medicine
Institute of Cancer Research
The Royal Marsden Hospital
15 Cotswold Road
Sutton, UK SM2 5NG
+44 (0) 20 8661 3993
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase I
Drug/device/biological/vaccine name(s)
ONX 0801
Primary outcome measure
1. To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ONX 0801 based on dose limiting toxicities (DLTs) occurring within cycle 1
2. To characterise the safety profile of ONX 0801
Secondary outcome measures
1. Pharmacokinetics (PK) of ONX 0801:
Blood samples will be collected according to the following schedule:
1.1. Cycle 1, Day 1: predose and 30 minutes and 1, 2, 3, 3.5, 4, 6, 8, 12, 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours following the start of the infusion
1.2. Cycle 1, Days 8 and 15: predose and 3 hours following the start of the infusion
1.3. Cycle 2, Days 1 and 8: predose and 3 hours following the start of the infusion
2. Pharmacodynamics of ONX 0801:
2.1. Blood samples will be collected according to the following schedule: predose and 4, 8, 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours following the start of infusion in Cycle 1, Day 1 and approximately every 6 - 9 weeks during the course of the study
2.2. Tissue samples may be collected predose and up to 72 hours following the start of the infusion in Cycle 1, Day 1
2.3. 18FLT-PET scans may be performed predose and between 16 to 48 hours following the start of the infusion in Cycle 1, Day 1
3. Identifying a biologically effective dose (BED) equal to or lower than the MTD and/or RP2D of ONX 0801
4. Assess the preliminary antitumour activity of ONX 0801
Overall study start date
30/09/2009
Overall study end date
30/03/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically or cytologically proven solid tumours, including lymphomas. Patients must have disease which has failed standard therapy or for which no standard curative therapy exists.
2. Greater than or equal to 18 years of age, either sex
3. Eastern Cooperative Oncology Group performance status (ECOG PS) less than or equal to 2
4. Life expectancy greater than or equal to 12 weeks
5. Measurable (as defined by Response Evaluation Criteria in Solid Tumours [RECIST version 1.1]) or evaluable (based on radiological assessments or tumour markers) disease
6. Recovered (i.e., to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 3.0 Grade less than or equal to 1) from all toxicities associated with previous chemotherapy or radiotherapy (exception: patients may enter with continuing alopecia irrespective of CTCAE grade). The following intervals between starting last treatment and starting ONX 0801 must elapse:
6.1. Chemotherapy (see exception below): at least 4 weeks
6.2. Mitomycin C or a nitrosourea: at least 6 weeks
6.3. Targeted therapy: at least 2 weeks or 2 half-lives, whichever is longer
6.4. Biologics: at least 4 weeks
6.5. Radiotherapy: at least 4 weeks
7. Normal organ function
8. Normal electrocardiogram (ECG)
9. Archival tumour tissue available
Participant type(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
60
Participant exclusion criteria
1. Pregnant women, women who are lactating, or women of childbearing potential who are not currently on effective means of birth control
2. History of QT/QTc prolongation, clinically significant ventricular tachycardia, ventricular fibrillation, heart block, myocardial infarction within 1 year, congestive heart failure New York Heart Association Class III or IV, unstable angina, angina within 6 months, or other evidence of clinically significant coronary artery disease
3. Active, ongoing infection, including viral hepatitis
4. Undergone major surgery within the last 4 weeks
5. Organ transplant recipients
6. New brain metastasis. Patients with treated (surgically excised or irradiated) and stable brain metastases are eligible as long as the treatment was at least 4 weeks prior to initiation of study drug and baseline brain computed tomography (CT) with contrast or magnetic resonance imaging (MRI) within 2 weeks of initiation of study drug is negative for new brain metastases.
7. Patients who have been on other experimental clinical trials of investigational agents within the last 28 days
Recruitment start date
30/09/2009
Recruitment end date
30/03/2011
Locations
Countries of recruitment
United Kingdom, United States of America
Study participating centre
2100 Powell Street
Emeryville
94608
United States of America
Sponsor information
Organisation
Onyx Pharmaceuticals (USA)
Sponsor details
2100 Powell Street
Emeryville
94608
United States of America
Sponsor type
Industry
Website
http://www.onyx-pharm.com/wt/page/index
ROR
Funders
Funder type
Industry
Funder name
Onyx Pharmaceuticals (USA)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|