Phase I Trial of ONX-0801 Once Weekly or Alternate Weekly (ONX-0801)
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|ClinicalTrials.gov Identifier: NCT02360345|
Recruitment Status : Completed
First Posted : February 10, 2015
Last Update Posted : March 9, 2021
This is an open label, single-centre dose escalation phase 1 clinical trial of ONX-0801.
The study will evaluate two schedules of ONX-0801 concurrently: once weekly and alternate week dosing, of repeated 28-day treatment cycles.
The study will consist of two stages: the dose escalation phase, in which the recommended phase II dose will be determined; and the expansion phase, in which up to 30 patients will be treated at the recommended phase II dose and schedule to further support the design of subsequent trials of ONX-0801.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumours||Drug: ONX-0801||Phase 1|
During the dose escalation phase, patients will be enrolled alternately to either:
- a q1wk schedule in which ONX-0801 will be administered over a 1-hour IV infusion on Days 1, 8, 15 and 22 of repeated 28-day treatment cycles; the starting dose will be 1 mg/m2 for the first cohort; OR
- a q2wk schedule in which ONX-0801 will be administered over a 1-hour IV infusion on Days 1 and 15 of repeated 28-day treatment cycles; the starting dose will be 2 mg/m2 for the first cohort;
Cohorts of 3 patients will receive ONX-0801 at escalating doses on each schedule until a Dose Limiting Toxicities (DLTs) occur and an Maximum Tolerated Dose (MTD) is determined for each schedule.
Once the recommended Phase II dose (RP2D) and schedule has been established, additional patients may be recruited in a dose expansion phase to a maximum total of 30 patients to further characterize safety, tolerability and pharmacodynamics. This subgroup of patients will be limited to those expected to have high rates of over expression of α-FR, such as patients with ovarian or endometrial, cancer.
Approximately 66 patients with solid tumours will be entered into this study.
Dose escalation: Approximately 18 patients in each schedule in the dose escalation phase. The final number for the dose escalation phase will depend on the number of dose escalations required to reach DLT.
Dose expansion: Up to 30 patients will be enrolled in the dose expansion phase, and this cohort will be enriched with patients with tumour types expected to have high rates of over expression of α-folate receptor, including ovarian and endometrial cancer. A minimum of 20 patients with platinum resistant/refractory ovarian cancer will be enrolled.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||111 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of ONX-0801 (a Novel α-folate Receptor-mediated Thymidylate Synthase Inhibitor) Exploring Once Weekly and Alternate Week Dosing Regimens in Patients With Solid Tumours|
|Actual Study Start Date :||September 2013|
|Actual Primary Completion Date :||January 2020|
|Actual Study Completion Date :||March 2021|
Experimental: q1week schedule
ONX-0801 will be administered over a 1-hour IV infusion on Days 1, 8, 15 and 22 of repeated 28-day treatment cycles.
Experimental: q2week schedule
ONX-0801 will be administered over a 1-hour IV infusion on Days 1 and 15 of repeated 28-day treatment cycles.
- Maximum Tolerated Dose [ Time Frame: 2 cycles (56 days) ]Establish the maximum tolerated dose of ONX-0801 when given on a weekly or alternate weekly schedule.
- Safety and Toxicity Profile 9adverse event to ONX-0801 and grading severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0) [ Time Frame: 2 cycles (56 days) ]Assign causality of each adverse event to ONX-0801 and grading severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
- Pharmacokinetic profile of ONX-0801 (Cmax, AUC and volume of distribution) [ Time Frame: 36 months ]Document Cmax, AUC and volume of distribution of ONX-0801 and determine if it is possible to achieve a plasma concentration of ≥ 0.05μM at the maximally tolerated dose in each schedule.
- Anti-tumour activity (disease response by RECIST criteria version 1.1) [ Time Frame: 36 months ]Determine disease response by RECIST criteria version 1.1, GCIC CA125 criteria and change in tumour size.
- Predictive Biomarkers (Analyse archival tumour tissue for α-FR) [ Time Frame: 36 months ]Analyse archival tumour tissue for α-FR as a predictive biomarker of disease response to ONX-0801. Correlate anti-tumour activity with the expression of α-FR
- Pharmacodynamic behaviour of ONX-0801 (levels of apoptosis markers (m30 and m65) in surrogate tissue) [ Time Frame: 36 months ]To determine the levels of apoptosis markers (m30 and m65) in surrogate tissue
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02360345
|The Royal Marsden NHS Foundation Trust|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Principal Investigator:||Udai Banerji, MBBS, PhD||The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust|