NCT03139331

PAZIT Study for Children and Young Adults With Relapsed or Refractory Sarcoma

Phase 1 Study of Pazopanib in Combination With Irinotecan and Temozolomide (PAZIT) for Children and Young Adults With Relapsed or Refractory Sarcoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 6 Years – 30 Years
• Healthy volunteers: Not accepted

Summary

This is the first study to evaluate the safety and clinical activity of the combination of oral pazopanib, intravenous or oral irinotecan, and oral temozolomide in pediatric and young adult patients with relapsed or refractory sarcomas. This study will use a 3 + 3 design for dose escalation (Part 1), followed by an expansion cohort (Part 2) at the recommended phase 2 dose level.

Detailed description

The combination of irinotecan and temozolomide is well-tolerated and provides an active therapy option for heavily pre-treated patients with sarcoma. The toxicity profile and activity level suggest that this combination will provide a useful platform onto which novel compounds may be added. Pazopanib has been shown to demonstrate single-agent activity in sarcomas in the preclinical and clinical settings. Pazopanib has also been shown to have additive or synergistic effects in preclinical models of sarcomas when combined with cytotoxic chemotherapy. Pharmacokinetic studies of pazopanib and irinotecan as well as pharmacodynamic studies of pazopanib to assess anti-angiogenesis will be performed. Exploratory studies to assess non-invasive methods of monitoring tumor response \[circulating tumor DNA and functional imaging by positron emission tomography (PET)/magnetic resonance imaging (MRI) will be performed\].

Conditions

• Sarcoma
• Refractory Sarcoma

Interventions

Type	Name	Description
DRUG	Pazopanib	Pazopanib will be administered orally as a tablet according to an assigned dose level per protocol. A cycle will be defined as 21 days. Drug dosing for the tablet formulation will be determined using a study-specific nomogram.
DRUG	Irinotecan	Patients will be given irinotecan at a dose of 25 mg/m2/dose IV on days 1-5 of a 21-day cycle during Cycle 1. In subsequent cycles, irinotecan may be given intravenously at a dose of 25 to 37.5 mg/m2/dose or orally at a dose of 45 to 67.5 mg/m2/dose on days 1-5 of a 21-day cycle. Note that some patients enrolled on an earlier protocol version received 50 mg/m2/dose IV on days 1-5 of the first 21-day cycle and then either 50 mg/m2/dose IV or 90 mg/m2/dose orally for subsequent 21-day cycles. This higher dose level is no longer being given to newly enrolled subjects.
DRUG	Temozolomide	Temozolomide will be given at a dose of 100 mg/m2/dose orally on days 1-5 of each 21-day cycle.

Timeline

• Start date: 2017-06-06
• Primary completion: 2019-10-15
• Completion: 2020-09-30
• First posted: 2017-05-03
• Last updated: 2021-01-05

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study