First-in-human Trial of PhOx430, a First-in-class Acetylglucosaminyltransferase V Inhibitor, in Advanced Solid Tumours
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorPhost'In Therapeutics
About this trial
The PhAST Trial is an adaptive first-in-human clinical trial of the acetylglucosaminyltransferase V inhibitor PhOx430 in patients with advanced solid tumours conceived and designed with the contribution of the Gianni Bonadonna Foundation, a non-profit academic research institution aimed at promoting therapeutic innovation in oncology.. The trial includes two parts, a dose escalation phase which will enroll patients with non-selected tumour types, followed by a cohort expansion phase in selected tumour types.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed diagnosis of cancer.
Dose escalation phase: patients with any solid tumour type or histology.
Expansion cohort 1: Patients affected by GBM.
Expansion cohort 2: Patients with triple-negative breast cancer (TNBC), defined as estrogen receptor (ER) negative (< 1% of nuclei reacting for ER in IHC), progesterone receptor (PgR) negative (< 1% of nuclei reacting for PgR in IHC), HER2 negative (IHC score = 0 or 1 or ICH score = 2 with FISH negative for HER2 overexpression. If only FISH was performed, negative result for HER2 overexpression).
Disqualifiers
Major surgery, chemotherapy, radical radiotherapy, investigational agents, or other anticancer therapy in the last 4 weeks before treatment start.
For all patients with the exception of GBM patients: active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and have been clinically stable for at least 3 months, and off steroids or anticonvulsants, before day 1 treatment).
For GBM patients: disease progression within three months following last prior radiation therapy.
Inability or unwillingness to swallow.
Trial design
Design model
Single group
Treatments tested in this trial
PhOx430
DrugA standard 3 + 3 design will be followed. PhOx430 will be administered orally twice a day (bid), at a 12-hour interval, continuously in cycles of 21 days. At each dose level (DL), three patients will be included and the first patient will be observed for at least 21 days before enrolling the following two. Three additional patients will be enrolled at each DL if a DLT is observed in the first three patients. A maximum of 4 increasing Dose Levels are foreseen (10, 20, 40 and 70 mg/kg/day), and PhOx430 will be administered in two doses at a 12-hour interval.
PhOx430
DrugThe implementation of this cohort (Step 3) was decided by the Protocol Steering Committee (PSC) based on clinical and pharmacokinetic data obtained in Steps 1 and 2. Six patients will be enrolled, who will receive PhOx430 orally thrice a day (tid) at a -6-hour interval over 12 hours for 21 days, and then, starting from day 22, four times a day (qid) at a 4-hour interval over 12 hours, continuously in cycles of 21 days. PhOx430 will be taken in single doses of 1,200 mg to patients weighing ≥ 50 kg and of 600 mg to patients weighing \< 50 kg, with no requirement for a full or empty stomach. The first patient will be observed after treatment start for at least 21 days before enrolling the following two. After the third patient is observed for 21 days after treatment start, 3 additional patients will be enrolled without waiting time between them. If the daily dose tested with the tid schedule is not deemed safe, the flat dose will be tested twice a day (bid) at a 12-hour interval.
Treatment groups
149 Participants
are divided into 1 treatment groupGroup A: Advanced Solid TumoursExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
DOSE ESCALATION PRIMARY OUTCOME (Dose Limiting Toxicities (DLTs))
Dose Limiting Toxicities (DLTs)
Time frame
At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)2
DOSE EXPANSION PRIMARY OUTCOME (treatment-emergent Adverse Events)
Incidence, severity and seriousness of treatment-emergent Adverse Events (AEs)
Time frame
Through study completion, up to 5 yearsSecondary outcomes
1
DOSE ESCALATION SECONDARY OUTCOME #1 (treatment-emergent Adverse Events)
Incidence, severity and seriousness of treatment-emergent Adverse Events (AEs)
Time frame
Through study completion, up to 5 years2
DOSE ESCALATION SECONDARY OUTCOME #2 (Plasma concentration levels of PhOx430)
Plasma concentration levels of PhOx430
Time frame
During Cycle1 and Cycle 2 (each cycle is 21 days)3
DOSE ESCALATION SECONDARY OUTCOME #3 (Objective response rate)
Objective response rate (ORR)
Time frame
Through dose escalation completion, an average of 1 year4
DOSE EXPANSION SECONDARY OUTCOME #1 (Plasma concentration levels of PhOx430 )
Plasma concentration levels of PhOx430
Time frame
During Cycle1 and Cycle 2 (each cycle is 21 days)Sponsors and contacts
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Source ClinicalTrials.gov