Clinical trial NCT04983238: Evaluation of Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With a Single Arm run-in Period to Evaluate the Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Byondis B.V.
Sponsor class: INDUSTRY
First posted: 2021-07-30
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This multicenter, randomized, double-blind, placebo-controlled trial with a single arm run-in period is to evaluate the safety and efficacy of sodium thiosulfate (BYON5667) eye drops to reduce ocular toxicity in cancer patients treated with the antibody-drug conjugate (ADC) SYD985

Detailed description: This multicenter trial has a single arm run-in period followed by a randomized, placebo-controlled, double-blind comparative part. In the single arm part of the trial, patients with HER2-expressing locally advanced or metastatic solid tumours will be enrolled and treated with the antibody-drug conjugate (ADC) SYD985 once every 3 weeks until disease progression or unacceptable toxicity. All patients will receive concomitant BYON5667 eye drops. When the primary safety and efficacy analysis of the BYON5667 eye drops at Day 63 is favorable, the trial may continue to the comparative part in which patients with locally advanced or metastatic HER2-positive breast cancer will be treated with SYD985. Patients will be randomly assigned (1:1) to receive BYON5667 or placebo eye drops.

Eligibility criteria: Main Inclusion Criteria:

1. Male or female, age ≥18 years at the time of signing first informed consent;
2. Patient with histologically-confirmed, unresectable locally advanced or metastatic cancer with the following restriction:

   Single arm part: patient with solid tumours of any origin (excluding gastric tumours and adenocarcinomas of the gastroesophageal junction) who has progressed on standard therapy or for whom no standard therapy exists; Randomized part: patient with breast cancer who had either progression during or after at least two human epidermal growth factor receptor 2 (HER2)-targeting treatment regimens for locally advanced or metastatic disease, or progression during or after \[ado-\]trastuzumab emtansine treatment for locally advanced or metastatic disease;
3. HER2 tumour status as determined by a local laboratory using immunohistochemistry (IHC) and/or in situ hybridization (ISH):

   Single arm part: at least IHC 1+; Randomized part: IHC 3+ and/or ISH positive;
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
5. Patient should refrain from wearing any kind of contact lenses during trial treatment;
6. Adequate organ function

Main Exclusion Criteria:

1. Current or previous use of prohibited medication as listed in the protocol
2. History of infusion-related reactions and/or hypersensitivity to trastuzumab containing treatment or excipients of the trial treatments which led to permanent discontinuation of the treatment;
3. History or presence of keratitis;
4. Left ventricular ejection fraction (LVEF) \< 50%, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment;
5. History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;
6. History or presence of clinically significant cardiovascular disease;
7. Severe, uncontrolled systemic disease;
8. Symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks.

Primary outcomes:
measure: Efficacy of BYON5667 eye drops by assessing the percentage of patients with SYD985-related ocular adverse events Grade >=1 at Day 63
timeFrame: 63 days
Secondary outcomes:
measure: Ocular toxicity
timeFrame: Day 63 or Day 126
measure: Tolerability of BYON5667 eye drops by means of Eye Drop Tolerability questionnaire scores
timeFrame: Up to 2 years
measure: National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores
timeFrame: Up to 2 years
measure: SYD985-related ocular adverse events (AE)
timeFrame: Up to 2 years
measure: Discontinuation due to SYD985-related ocular toxicity
timeFrame: Up to 2 years
measure: Efficacy of SYD985 by assessing the objective response rate (ORR)
timeFrame: Up to 2 years
measure: Efficacy of SYD985 by assessing the progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Efficacy of SYD985 by assessing the overall survival
timeFrame: Up to 2 years
measure: Safety of SYD985 by assessing incidence and severity of treatment-emergent drug-related adverse events
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Leuven
country: Belgium
facility: UZ Leuven
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lille
country: France
facility: Centre Oscar Lambret
city: Paris
country: France
facility: Hôpital Saint Louis
city: Barcelona
country: Spain
facility: Vall d' Hebron
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO I'Hospitalet - Hospital Duran i Reynals
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: START Madrid HU Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START Madrid HU HM Sanchinarro
Study officials:
affiliation: Byondis B.V., The Netherlands
name: Ellen Mommers, PhD
role: STUDY_DIRECTOR
References: