Phase I Trial of ONX-0801 Once Weekly or Alternate Weekly

NCT02360345 | Completed Phase 1

• 2 other identifiers: CCR39412013-000569-34
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumours

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Establish the maximum tolerated dose of ONX-0801 when given on a weekly or alternate weekly schedule.

  2 cycles (56 days)

• 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)

  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

  2 cycles (56 days)

Secondary Outcomes (1)

• Pharmacokinetic profile of ONX-0801 (Cmax, AUC and volume of distribution)

  36 months

Other Outcomes (3)

• Anti-tumour activity (disease response by RECIST criteria version 1.1)

  36 months

• Predictive Biomarkers (Analyse archival tumour tissue for α-FR)

  36 months

• Pharmacodynamic behaviour of ONX-0801 (levels of apoptosis markers (m30 and m65) in surrogate tissue)

  36 months

Study Arms (2)

q1week schedule

EXPERIMENTAL

ONX-0801 will be administered over a 1-hour IV infusion on Days 1, 8, 15 and 22 of repeated 28-day treatment cycles.

Drug: ONX-0801

q2week schedule

EXPERIMENTAL

ONX-0801 will be administered over a 1-hour IV infusion on Days 1 and 15 of repeated 28-day treatment cycles.

Drug: ONX-0801

Interventions

ONX-0801 DRUG

q1week schedule; q2week schedule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically proven solid tumours (to include Non-Hodgkin's and Hodgkin's lymphoma). Patients must have disease which has failed standard therapy or for whom no standard curative therapy exists. At the dose expansion phase, entry will be limited to patients with ovarian and endometrial cancers with availability of archival paraffin embedded tissue
• Measurable (as defined by RECIST version 1.1) or evaluable (based on tumour markers) disease
• Life expectancy of at least 12 weeks
• World Health Organisation (WHO) performance status of 0-1 (Appendix 1)
• Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient goes in the trial.
• Laboratory Test Value required Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible Serum creatinine ≤ 1.5 x ULN PT and APTT ≤ 1.25x ULN
• Normal (no clinically significant abnormalities) 12-lead ECG, QTc interval \<470 ms
• Pulmonary function test FVC of \>70%, DLCOc (DLCO corrected for Hb) of \>60%
• years or over
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

You may not qualify if:

• Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.
• Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the DDU should not exclude the patient
• Patients with new brain metastases. 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 brain MRI within 2 weeks of initiation of study drug is negative for new metastases.
• Patients with pulmonary metastases
• History of thoracic radiation or other history likely to create pre-existing lung disease
• Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible..
• Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception \[condom plus spermicide\] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• Patients with sub-acute bowel obstruction
• Patients using heparin, or warfarin/coumadin type anticoagulants, however, low-dose (\<2mg) coumadin for portacath patency is allowed;
• Organ transplant recipients
• Patients with known systemic disease with pulmonary involvement, including active uncontrolled infection.
• Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• Patients with history of QT prolongation, clinically significant VT, VF, heart block, MI within 1 year, CHF NYHA Class III or IV, unstable angina, angina within 6 months, or other evidence of clinically significant coronary artery disease
• Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I study of ONX-0801. Participation in an observational trial would be acceptable.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Institute of Cancer Research, United Kingdom: collaborator
• Onyx Therapeutics, Inc.: collaborator

Study Sites (1)

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Banerjee S, Michalarea V, Ang JE, Ingles Garces A, Biondo A, Funingana IG, Little M, Ruddle R, Raynaud F, Riisnaes R, Gurel B, Chua S, Tunariu N, Porter JC, Prout T, Parmar M, Zachariou A, Turner A, Jenkins B, McIntosh S, Ainscow E, Minchom A, Lopez J, de Bono J, Jones R, Hall E, Cook N, Basu B, Banerji U. A Phase I Trial of CT900, a Novel alpha-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer. Clin Cancer Res. 2022 Nov 1;28(21):4634-4641. doi: 10.1158/1078-0432.CCR-22-1268.

  PMID: 35984704 RESULT

MeSH Terms

Interventions

BGC945

Study Officials

• Udai Banerji, MBBS, PhD

  The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 10, 2015
• Study Start: September 1, 2013
• Primary Completion: January 1, 2020
• Study Completion: March 1, 2021
• Last Updated: September 26, 2024

Record last verified: 2024-09

Locations

GB (1)