Safety and Efficacy of INCB007839 With Trastuzumab and Vinorelbine in Patients With Metastatic HER2+ Breast Cancer - Full Text View

Purpose

This Phase I/II study is designed to assess the safety and therapeutic effect of INCB007839 in combination with trastuzumab and vinorelbine in patients with metastatic HER2+ breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: INCB007839 300mg BID Drug: Trastuzumab Drug: Vinorelbine	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study to Assess the Safety and Therapeutic Effect of INCB007839 in Combination With Trastuzumab and Vinorelbine in Patients With Metastatic HER2+ Breast Cancer.

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Vinorelbine Vinorelbine tartrate Trastuzumab

U.S. FDA Resources

Further study details as provided by Incyte Corporation:

Primary Outcome Measures:

Evaluation of safety and tolerabilty as determined by monitoring the frequency and severity of adverse events (AEs) and performing clinical assessments and laboratory investigations. [ Time Frame: Measured monthly starting at Baseline (estimated duration 6-9 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall objective response rate assessed by RECIST criteria [ Time Frame: Measured at Baseline, Cycle 4 and approximately every 9 weeks after (estimated duration 6-9 months) ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	October 2010
Study Completion Date:	October 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment A - INCB007839 300mg BID This is a single arm, open label study in which all patients will receive a single dose of the investigational product INCB007839 in combination with a standard regimen of trastuzumab and vinorelbine.	Drug: INCB007839 300mg BID INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met. Drug: Trastuzumab INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met. Drug: Vinorelbine INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.

Arms

Assigned Interventions

Experimental: Treatment A - INCB007839 300mg BID

This is a single arm, open label study in which all patients will receive a single dose of the investigational product INCB007839 in combination with a standard regimen of trastuzumab and vinorelbine.

Drug: INCB007839 300mg BID

INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.

Drug: Trastuzumab

INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.

Drug: Vinorelbine

INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject with diagnosis of metastatic (or locally recurrent-inoperable) breast cancer
Subject with histological HER2+ status as determined by FISH with a gene amplification score of ≥ 2.2
Subject with availability of archival biopsy tissue from primary tumor or metastatic lesions
Subject with presence of measurable disease based on RECIST 1.1
Subject who has received no more than three prior HER2-directed therapeutic regimens for advanced breast cancer

Exclusion Criteria:

Subject with Left ventricular ejection fraction (LVEF) below institutional normal range
Subject with metastasis to the central nervous system UNLESS asymptomatic and clinically stable
Subject with current active malignancy other than breast cancer
Subject with prior history of other malignancy except for cancers from which the patient is currently disease free
Subject with significant renal or hepatic dysfunction
Subject with history of venous or arterial thrombosis or risk factor for thrombosis other than history of malignancy
Subject with insufficient bone marrow function
Subject with contraindication to vinorelbine, trastuzumab, aspirin and/or warfarin therapy.
Subject with current active bacterial, Hepatitis B or C, and/or HIV infections

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01254136

Locations

United States, Arkansas

Fayetteville, Arkansas, United States
United States, California

Duarte, California, United States
United States, Colorado

Denver, Colorado, United States
United States, Florida

Davie, Florida, United States

Jacksonville, Florida, United States
United States, Michigan

Detroit, Michigan, United States
United States, Missouri

St. Louis, Missouri, United States
United States, New Jersey

Hackensack, New Jersey, United States
United States, New York

Lake Success, New York, United States
United States, North Carolina

Huntersville, North Carolina, United States
United States, Ohio

Cincinnati, Ohio, United States
United States, Pennsylvania

Philadelphia, Pennsylvania, United States
United States, Tennessee

Nashville, Tennessee, United States
United States, Utah

Salt Lake, Utah, United States

Sponsors and Collaborators

Incyte Corporation

Investigators

Principal Investigator:

Denise A. Yardley, MD

Sara Cannon Research Institute

More Information

No publications provided

Responsible Party:	Incyte Corporation
ClinicalTrials.gov Identifier:	NCT01254136 History of Changes
Other Study ID Numbers:	INCB 7839-204
Study First Received:	December 1, 2010
Last Updated:	January 20, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vinorelbine
Vinblastine
Trastuzumab

Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013