A phase I study to evaluate the safety and pharmacokinetics of ONX 0801 in advanced solid tumours

ISRCTN	ISRCTN79302332
DOI	https://doi.org/10.1186/ISRCTN79302332
Protocol serial number	2009-001
Sponsor	Onyx Pharmaceuticals (USA)
Funder	Onyx Pharmaceuticals (USA)

Submission date: 12/06/2009
Registration date: 30/06/2009
Last edited: 12/12/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Lynne Bui
Scientific

2100 Powell Street
Emeryville
94608
United States of America

Study information

Primary study design	Interventional
Study design	Phase I open-label dose-finding study
Secondary study design	Non randomised study
Study type	Participant information sheet
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
Study objectives	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
Health condition(s) or problem(s) studied	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
Phase	Phase I
Drug / device / biological / vaccine name(s)	ONX 0801
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	30/03/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	60
Key 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
Key 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
Date of first enrolment	30/09/2009
Date of final enrolment	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

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

12/12/2017: No publications found in PubMed, verifying study status with principal investigator.