Open Label Trial of INCB07839 to Determine Effect and Safety of INCB007839 Plus Trastuzumab in HER2 Positive Metastatic Breast Cancer

Phase 1

Terminated

• Conditions: Breast Cancer
• Interventions: Drug: INCB007839; Drug: trastuzumab; Drug: Docetaxel

• Registration Number: NCT00864175
• Lead Sponsor: Incyte Corporation

Brief Summary

This is a single arm, modified dose escalation, open label trial with the objectives of: (1) Determining a safe optimal dose of INCB007839 in combination with trastuzumab and docetaxel (2) Determining clinical efficacy and safety of INCB007839 in combination with trastuzumab and docetaxel.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2009-01-26
• Study First Submitted QC: 2009-03-17
• Study First Posted: 2009-03-18
• Disposition First Submitted: 2010-06-18
• Disposition First Submitted QC: 2010-06-18
• Disposition First Posted: 2010-06-22
• Primary Completion: 2011-06
• Study Completion: 2011-10
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-16
• Last Update Posted: 2018-01-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 68

Inclusion Criteria

• Histologically or cytologically confirmed metastatic breast carcinoma that is HER2 positive
• Measurable disease as defined by the RECIST criteria
• Life expectancy greater than or equal to 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria

• Received any anticancer medications in the 28 days prior to enrollment into this study
• Received any anticancer medications for cancers other than breast cancer within 6 months prior to enrollment in this study.
• History of deep venous thrombosis within the last year
• Contraindication to low dose warfarin therapy
• Clinically significant cardiomyopathy
• Prior treatment with INCB007839 or trastuzumab or lapatinib

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment A - INCB007839 and Trastuzumab	trastuzumab	INCB007839 100 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.
Treatment B - INCB007839 and Trastuzumab	INCB007839	INCB007839 200 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.
Treatment B - INCB007839 and Trastuzumab	trastuzumab	INCB007839 200 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.
Treatment C - INCB007839 and Trastuzumab	INCB007839	INCB007839 300 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.
Treatment A - INCB007839 and Trastuzumab	INCB007839	INCB007839 100 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.
Treatment D - INCB007839 and Docetaxel	INCB007839	INCB007839 300mg BID with docetaxel
Treatment D - INCB007839 and Docetaxel	Docetaxel	INCB007839 300mg BID with docetaxel
Treatment C - INCB007839 and Trastuzumab	trastuzumab	INCB007839 300 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.

Primary Outcome Measures

Name	Time	Method
Overall response rate (complete + partial response) using RECIST (Response Evaluation Criteria in Solid Tumor) criteria	Day 1 of each completed subsequent 21-day treatment cycle and the End of Study Visit.

Secondary Outcome Measures

Name	Time	Method
To determine the plasma pharmacokinetic (PK) profile of INCB007839 and trastuzumab when given in combination	Monthly	For Cycle 1, PK samples to be collected on Day 8 and Day 15 at pre-dose the morning dose of INCB007839. For Cycles 2, 3 and 4, PK will be collected as a single sample, obtained at pre-dose, on Day 1. PK samples will not be collected at Cycle 5 or later.; o. For Cycle 1, PD samples to be collected at time of screening and at pre-dose on Day 1, Day