Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer

Phase 1

Completed

• Conditions: Ovarian Cancer
• Interventions: Drug: Fostamatinib 100 mg bid and Paclitaxel; Drug: Fostamatinib 150 mg bid and Paclitaxel; Drug: Fostamatinib 200 mg bid and Paclitaxel

• Registration Number: NCT03246074
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

This research is being done to test the safety of the combination of the study drugs fostamatinib and paclitaxel. This study tests different doses of the drugs to see which doses are safest in people with ovaria cancer when given together.

Detailed Description

This is a phase I, open-label, non-randomized multicenter dose-escalation study with the primary objective to determine the maximally tolerated dose (MTD) of fostamatinib when administered with weekly paclitaxel in women with recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.

Between 8 and 18 adult female subjects will be enrolled and receive weekly paclitaxel in combination with increasing doses of fostamatinib. There will be three dosing intervals of fostamatinib (100 mg bid, 150 mg bid, and 200mg bid) selected based on prior phase I studies of single agent fostamatinib. Dose-escalation will follow a modified toxicity probability interval (mTPI) design. In this study, up to 18 adult female subjects will be enrolled and receive weekly paclitaxel in combination with fostamatinib at the MTD of the combination; at least 6 patients with receive fostamatinib plus paclitaxel at the MTD.

Study Timeline

• Study First Submitted: 2017-06-15
• Study First Submitted QC: 2017-08-09
• Study First Posted: 2017-08-11
• Study Start: 2018-04-03
• Primary Completion: 2022-08-09
• Study Completion: 2023-04-03
• Results First Submitted: 2024-03-11
• Results First Submitted QC: 2024-09-03
• Results First Posted: 2024-09-19
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-21
• Last Update Posted: 2024-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fostamatinib 100 mg bid and Paclitaxel	Fostamatinib 100 mg bid and Paclitaxel	Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose of 100mg twice daily throughout each 28-day cycle.
Fostamatinib 150 mg bid and Paclitaxel	Fostamatinib 150 mg bid and Paclitaxel	Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose of 150mg twice daily throughout each 28-day cycle.
Fostamatinib 200 mg bid and Paclitaxel	Fostamatinib 200 mg bid and Paclitaxel	Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose of 150mg twice daily throughout each 28-day cycle.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of Fostamatinib	First cycle (28 days) of treatment	The number of dose limiting toxicities (DLTs) at each dose level will be reported. All toxicities will be reported by type and grade using NCI CTCAE version 4.03.
Maximum Tolerated Dose (MTD) of Fostamatinib	28 days	The MTD will be determined as the dose level with the highest probability of having a risk of DLT in the acceptable region based on the mTPI dose-escalation design. Measured at 28 days (DLT period).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel	5 years	Number of participants within each objective response as seen on imaging/RECIST 1.1. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Progression-free Survival in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel	5 years	Progression-free survival (PFS) will be described by the method of Kaplan and Meier. Median PFS in months will be estimated along with its 95% confidence interval. Per response evaluation criteria in solid tumors (RECIST v1.1), Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Tmax	First cycle (28 days) of treatment	Tmax (hours) was used to summarize pharmacokinetic marker profile for fostamatinib. Tmax (hours): Time to reach maximum plasma concentration of R406, the active meta
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Cmax	First cycle (28 days) of treatment	Cmax (ng/mL) was used to summarize pharmacokinetic marker profile for fostamatinib. Cmax (ng/mL): Maximum plasma concentration of R406.
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Area Under the Curve (AUC) 0-6hours	First cycle (28 days) of treatment	AUC0-6h (ng\*h/mL) was used to summarize pharmacokinetic marker profile for fostamatinib. AUC0-6h (ng\*h/mL): Area under the concentration-time curve for R406 up to 6 hours post-dosing.

Trial Locations

Locations (3)

Sibley Memorial Hospital; 🇺🇸 Washington, District of Columbia, United States

University of Pennsylvania Health System; 🇺🇸 Philadelphia, Pennsylvania, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States