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Studies

Interventional Active not recruiting Phase 1/Phase 2

NCT05180695 on ClinicalTrials.gov

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

Official title: 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)

  • Sponsor: Centre Léon Bérard
  • Collaborators: Novartis, National Cancer Institute, France
  • Enrollment: 47 (Actual)
  • Study start: 2022-04-15 (Actual)
  • Primary completion: 2027-02-01 (Estimated)
  • Study completion: 2027-02-01 (Estimated)
  • Allocation: Non-Randomized
  • InterventionModel: Sequential
  • InterventionModelDescription: The dose escalation will be conducted according to a sequential and adaptive Bayesian scheme, using the method of TITE-CRM to determine the MTD of pazopanib in combination with HDM 201. This method allows continual accrual (i.e. the study will be opened to accrual continually) throughout the trial while using the 6-week toxicity endpoint as basis of dose escalation. Dose allocation will be centrally defined, before each inclusion considering the DLT observed in all patients previously evaluated, and the current toxicity status of patients who have not received a full 2-cycle treatment (i.e. DLT period is still ongoing). * A cumulative experience of 4 cycles at a given DL is required before allowing dose escalation to the next DL. Cumulative experience is defined as the addition of observation periods of all included and treated patients. * A maximum of 6 patients can be included and treated at a same dose level before reassessment occurred.
  • Masking: None
  • PrimaryPurpose: Treatment

Brief 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.

Conditions

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

Intervention / Treatment

  • Drug: Pazopanib
  • Drug: HDM201

Primary Outcome Measures

  • for dose escalation part: the Maximum tolerated dose (MTD) of HDM201 given in combination with a fixed dose of pazopanib. (At the end of cycle 2 (each cycle is 21 days))
    The starting dose of HDM201 is 60 mg once every 3 weeks. The dose escalation will be conducted according to a sequential and adaptive Bayesian scheme, using the method of TITE-CRM to determine the MTD of HDM201 in combination with pazopanib. The MTD is defined as the dose associated with a probability of Dose Limiting toxicities (DLTs) the closest to 25%. Estimation of MTD will be based upon the estimation of the probability of a DLT. DLTs are defined as any of the following adverse events (AE) graded using NCI-CTCAE occurring during the DLT period (2 first cycles) and assessed as related to at least one of the study drugs: Grade (G) ≥ 4 neutropenia, G ≥ 3 febrile neutropenia, G ≥ 4 thrombocytopenia or G3 if associated with bleeding and requires platelet transfusion. Non-laboratory AEs of G ≥3 for more than 7 days. Any G3 or G4 laboratory value if: Medical intervention is required to treat the subjects, or the abnormality leads to hospitalization.
  • Expansion part: preliminary data on efficacy of the combination in 2 parallel, independent cohorts of Soft-tissue sarcomas according to Murine double minute 2 (MDM2) status: amplified and non-amplified. (24W)
    progression-free rate at 24 weeks (24W-PFR)

Countries

France

Locations and Investigators