NCT05180695

HDM201 and Pazopanib in Patients With P53 Wild-type Advanced/Metastatic Soft Tissue Sarcomas

A Multicenter, Phase I/II Study Evaluating the Clinical Impact of HDM201 + Pazopanib in Patients With P53 Wild-type Advanced/ Metastatic Soft Tissue Sarcomas (AMPHISARC)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial is a two-step Phase I/II study comprising: Part 1: A dose escalation part with the aim to assess the safety of the proposed combination (N= up to 30 patients). In the dose escalation part, eligible patients will be treated with a fixed dose of pazopanib and escalating doses of HDM201. Part 2: An extension part to collect preliminary data about the clinical activity of the proposed combination according to the 6M-PFR.

Detailed description

This trial is a two-step Phase I/II study comprising: Part 1: A dose escalation part with the aim to assess the safety of the proposed combination (N= up to 30 patients). The dose escalation will be conducted according to a sequential and adaptive Bayesian scheme using the method of Time-to-event Continual Reassessment Method (CRM) to guide dose escalation and estimate the Maximum Tolerated Dose. In the dose escalation part, eligible patients will be treated with a fixed dose of pazopanib (800 mg/d) and escalating doses of HDM201: 60 mg (starting dose); 80 mg; 100 mg; 120 mg. For a safety reason, a dose level of 40 mg is included in case that the first dose level is found to be toxic. In addition, decrease of pazopanib dosing to 600 mg/d could be appropriate following protocol amendment. To ensure adequate patient safety during the dose escalation part, there will be a 3-day delay between the first and subsequent patients enrolled in each DL cohort to maximize the safety of enrolled patients. No intra-patient dose escalation is allowed. Part 2: An extension part to collect preliminary data about the clinical activity of the proposed combination according to the 6 months Progression Free Rate (6M-PFR).

Conditions

• Advanced Soft-tissue Sarcoma
• Metastatic Soft-tissue Sarcoma

Interventions

Type	Name	Description
DRUG	Pazopanib	Part 1: A dose escalation part with the aim to assess the safety of the proposed combination. Eligible patients will be treated with a fixed dose of pazopanib (800mg/d, continuously) and escalating doses of HDM201. Both study drugs will be administered as long as the patient experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression or withdrawal of consent. Part 2: An extension part with a fixed dose of pazopanib (800mg/d, continuously) and the recommended phase 2 dose of HDM201 determined during the dose escalation part. Both study drugs will be administered as long as the patient experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression or withdrawal of consent.
DRUG	HDM201	Part 1: A dose escalation part with the aim to assess the safety of the proposed combination. Eligible patients will be treated with a fixed dose of pazopanib (800mg/d, continuously) and escalating doses of HDM201. Both study drugs will be administered as long as the patient experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression or withdrawal of consent. Part 2: An extension part with a fixed dose of pazopanib (800mg/d, continuously) and the recommended phase 2 dose of HDM201 determined during the dose escalation part. Both study drugs will be administered as long as the patient experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression or withdrawal of consent.

Timeline

• Start date: 2022-04-15
• Primary completion: 2027-02-01
• Completion: 2027-02-01
• First posted: 2022-01-06
• Last updated: 2026-02-10

Locations

5 sites across 1 country: France