Ignite Creation Date:
2025-12-24 @ 2:19 PM
Ignite Modification Date:
2026-02-25 @ 6:35 PM
Study NCT ID:
NCT05495295
Status:
RECRUITING
Last Update Posted:
2025-04-08
First Post:
2022-07-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
First-in-human Trial of PhOx430, a First-in-class Acetylglucosaminyltransferase V Inhibitor, in Advanced Solid Tumours
Sponsor:
Phost'In Therapeutics
Organization:
Study Overview
Official Title:
An Adaptive First-in-human Trial of PhOx430, a First-in-class Acetylglucosaminyltransferase V Inhibitor, in Patients With Advanced Solid Tumours (PhAST Trial)
Status:
RECRUITING
Status Verified Date:
2025-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PhAST
Brief Summary:
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.
Detailed Description:
The PhAST Trial is a first-in-human clinical trial of the acetylglucosaminyltransferase V inhibitor PhOx430 in patients with advanced solid tumours. The trial includes two parts, a dose escalation phase (part I) which will enroll patients with non-selected tumour types, followed by a cohort expansion phase (part II) in selected tumour types.
POPULATION:
Adult patients with advanced or metastatic solid malignancies with radiologically documented progression on a previous line of treatment and for which effective treatment options do not exist.
DOSE ESCALATION'S PRIMARY OBJECTIVE:
To determine the Maximal Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of PhOx430 in patients with advanced solid tumours
DOSE ESCALATION'S SECONDARY OBJECTIVE:
1. to determine the safety and tolerability profile of PhOx430 at increasing dose levels;
2. to characterize the pharmacokinetic (PK) profile of PhOx430, including food effect on drug disposition;
3. to evaluate the antitumour activity of PhOx430.
DOSE ESCALATION'S EXPLORATORY OBJECTIVE:
4. to characterize the pharmacodynamics (PD) effect of PhOx430 on blood, urine and tumour samples collected before and after treatment;
5. to identify predictive response biomarkers by profiling responsive patterns.
DOSE EXPANSIONS' PRIMARY OBJECTIVE:
To better characterize the safety and tolerability profile of PhOx430 given at the RP2D in three cohorts of patients affected by 1) glioblastoma multiforme (GBM), 2) triple-negative breast cancer, and 3) selected types of solid tumours.
DOSE EXPANSION'S SECONDARY OBJECTIVE:
1. to characterize the pharmacokinetic (PK) profile of PhOx430 at the RP2D.
2. to evaluate the antitumour activity of PhOx430 in the specific tumour types selected for the dose expansion cohorts.
DOSE EXPANSIONS' EXPLORATORY OBJECTIVE:
3. to characterize the pharmacodynamic (PD) effect of PhOx430 on blood, urine and tumour samples collected before and after treatment;
4. to identify predictive response biomarkers by profiling responsive patterns.
STUDY DESIGN AND TREATMENT PLAN:
Dose Escalation Phase - STEP 1-2: a 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), at least three patients will be included and the first patient will be observed for at least 21 days before enrolling the following two.
Dose Escalation Phase - STEP 3 (Dosing-optimization Cohort): The implementation of this Dosing-optimization 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 be administered a flat dose of PhOx430 (1,200 mg by patients weighing ≥ 50 kg and of 600 mg by patients weighing \< 50 kg) orally thrice a day (tid) for 21 days, and then, starting from day 22, four times a day (qid), continuously in cycles of 21 days. 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, three additional patients will be enrolled without waiting time between them. In case the daily dose tested with the tid schedule is not deemed safe, the flat dose of PhOx430 will be tested twice a day (bid).
Cohort Expansion Phase: in the cohort expansion phase, the safety profile of PhOx430 will be further characterized by testing the RP2D in three parallel cohorts of patients affected by glioblastoma multiforme (GBM) (cohort 1), triple-negative breast cancer (TNBC) (cohort 2), and solid tumour types selected by the Protocol Steering Committee (PSC) on the basis of preclinical pharmacological data and of the antitumour activity observed during the Dose Escalation Phase if any (cohort 3), respectively. Cycles will be of 21 days.
ESTIMATED TRIAL DURATION and SAMPLE SIZE:
Dose Escalation Phase Step 1,2,3: approximately 1.5 years Expansion Phase: approximately 1.5 years. The end of trial is defined as 30 days after the last dose of the last enrolled patient.
The following numbers of patients are foreseen: up to 149 patients.
POPULATION:
Adult patients with advanced or metastatic solid malignancies with radiologically documented progression on a previous line of treatment and for which effective treatment options do not exist.
DOSE ESCALATION'S PRIMARY OBJECTIVE:
To determine the Maximal Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of PhOx430 in patients with advanced solid tumours
DOSE ESCALATION'S SECONDARY OBJECTIVE:
1. to determine the safety and tolerability profile of PhOx430 at increasing dose levels;
2. to characterize the pharmacokinetic (PK) profile of PhOx430, including food effect on drug disposition;
3. to evaluate the antitumour activity of PhOx430.
DOSE ESCALATION'S EXPLORATORY OBJECTIVE:
4. to characterize the pharmacodynamics (PD) effect of PhOx430 on blood, urine and tumour samples collected before and after treatment;
5. to identify predictive response biomarkers by profiling responsive patterns.
DOSE EXPANSIONS' PRIMARY OBJECTIVE:
To better characterize the safety and tolerability profile of PhOx430 given at the RP2D in three cohorts of patients affected by 1) glioblastoma multiforme (GBM), 2) triple-negative breast cancer, and 3) selected types of solid tumours.
DOSE EXPANSION'S SECONDARY OBJECTIVE:
1. to characterize the pharmacokinetic (PK) profile of PhOx430 at the RP2D.
2. to evaluate the antitumour activity of PhOx430 in the specific tumour types selected for the dose expansion cohorts.
DOSE EXPANSIONS' EXPLORATORY OBJECTIVE:
3. to characterize the pharmacodynamic (PD) effect of PhOx430 on blood, urine and tumour samples collected before and after treatment;
4. to identify predictive response biomarkers by profiling responsive patterns.
STUDY DESIGN AND TREATMENT PLAN:
Dose Escalation Phase - STEP 1-2: a 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), at least three patients will be included and the first patient will be observed for at least 21 days before enrolling the following two.
Dose Escalation Phase - STEP 3 (Dosing-optimization Cohort): The implementation of this Dosing-optimization 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 be administered a flat dose of PhOx430 (1,200 mg by patients weighing ≥ 50 kg and of 600 mg by patients weighing \< 50 kg) orally thrice a day (tid) for 21 days, and then, starting from day 22, four times a day (qid), continuously in cycles of 21 days. 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, three additional patients will be enrolled without waiting time between them. In case the daily dose tested with the tid schedule is not deemed safe, the flat dose of PhOx430 will be tested twice a day (bid).
Cohort Expansion Phase: in the cohort expansion phase, the safety profile of PhOx430 will be further characterized by testing the RP2D in three parallel cohorts of patients affected by glioblastoma multiforme (GBM) (cohort 1), triple-negative breast cancer (TNBC) (cohort 2), and solid tumour types selected by the Protocol Steering Committee (PSC) on the basis of preclinical pharmacological data and of the antitumour activity observed during the Dose Escalation Phase if any (cohort 3), respectively. Cycles will be of 21 days.
ESTIMATED TRIAL DURATION and SAMPLE SIZE:
Dose Escalation Phase Step 1,2,3: approximately 1.5 years Expansion Phase: approximately 1.5 years. The end of trial is defined as 30 days after the last dose of the last enrolled patient.
The following numbers of patients are foreseen: up to 149 patients.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2021-004170-55 | EUDRACT_NUMBER | None | View |