Phase I Dose Escalation Study of Topotecan and Pazopanib in Children With Recurrent/Refractory Solid Tumours

Phase 1

Completed

• Conditions: Solid Tumors
• Interventions: Drug: Topotecan and Pazopanib

• Registration Number: NCT02303028
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

This is a phase I, dose escalation study where topotecan will be administered at lower doses given more frequently on a prolonged schedule (low dose metronomic; LDM), in combination with pazopanib administered in a specific dose range. The maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) will be evaluated for LDM topotecan in combination with pazopanib in children with recurrent or refractory solid tumours. Pharmacokinetic and pharmacodynamic studies will be conducted to further define the exposure to and activity of LDM topotecan in combination with pazopanib.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-25
• Study First Submitted QC: 2014-11-25
• Study First Posted: 2014-11-27
• Study Start: 2015-03
• Status Verified: 2022-06
• Primary Completion: 2022-06-17
• Study Completion: 2022-06-17
• Last Update Submitted: 2022-06-27
• Last Update Posted: 2022-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Topotecan and Pazopanib	Topotecan and Pazopanib	Low dose Topotecan will be given metronomically in combination with Pazopanib at the dose level assigned at study entry

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of low dose metronomic (LDM)Topotecan	Dose limiting toxicities (DLT) will be identified during the first cycle of therapy (28 days)	MTD is dependent on the number of subjects who experience a DLT at a given dose level
Recommended phase 2 dose (RP2D) of LDM Topotecan	Dose limiting toxicities (DLT) will be identified during the first cycle of therapy (28 days)	The RP2D will be defined as the highest dose, at or below the MTD, at which the median number of cycles tolerated by subjects is ≥ 3.

Secondary Outcome Measures

Name	Time	Method
Anti-tumour activity of LDM Topotecan in combination with Pazopanib	24 months	To preliminarily define the anti-tumour activity of LDM Topotecan in combination with pazopanib in pediatric solid tumours within the confines of a phase 1 study, and more specifically in cohorts of children with i) neuroblastoma and ii) rhabdomyosarcoma
Anti-angiogenic activity of LDM Topotecan and Pazopanib	24 months	To assess the anti-angiogenic activity of this regimen by evaluating changes in plasma cytokines and angiogenic factors (CAF).
Pharmacokinetics of LDM Topotecan and Pazopanib	24 months	To characterize the pharmacokinetics of LDM Topotecan and Pazopanib, as well as any drug-drug interactions

Trial Locations

Locations (10)

Children's Hospital, London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

McMaster Children's Hospital; 🇨🇦 Hamilton, Ontario, Canada

IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

BC Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Children's Hospital of Eastern Ontario (CHEO); 🇨🇦 Ottawa, Ontario, Canada

Janeway Child Health Centre; 🇨🇦 Saint John's, Newfoundland and Labrador, Canada

CHU St. Justine Hopital; 🇨🇦 Montreal, Quebec, Canada