Trial Outcomes & Findings for Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer (NCT NCT00470847)

Last Updated: 2014-05-22

Results Overview

The maximum tolerated dose is defined as :The highest dose of a drug or treatment that does not cause unacceptable side effects.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

5 Years

Results posted on

2014-05-22

Participant Flow

Participants were recruited between May 2007 and December 2009.

Participant milestones

Participant milestones
Measure	Lapatinib,Whole Brain Radiation,Herceptin Participants received lapatinib, orally, 750mg twice on day one followed by 1000mg, 1250mg, or 1500mg once daily. Whole Brain Radiation therapy (WBRT) (37.5 Gy, 15 fractions) began 1-8 days after starting lapatinib. Lapatinib was continued through WBRT. Following WBRT, patients received trastuzumab intravenously 2mg/kg weekly and lapatinib 1000mg orally once daily.
Overall Study STARTED	35
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Lapatinib,Whole Brain Radiation,Herceptin Participants received lapatinib, orally, 750mg twice on day one followed by 1000mg, 1250mg, or 1500mg once daily. Whole Brain Radiation therapy (WBRT) (37.5 Gy, 15 fractions) began 1-8 days after starting lapatinib. Lapatinib was continued through WBRT. Following WBRT, patients received trastuzumab intravenously 2mg/kg weekly and lapatinib 1000mg orally once daily.
Overall Study Pt still receiving treatment	1

Baseline Characteristics

Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=35 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Age, Customized Between 30 and 78	35 participants n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 Years

The maximum tolerated dose is defined as :The highest dose of a drug or treatment that does not cause unacceptable side effects.

Outcome measures

Outcome measures
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=35 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
The Maximum Tolerated Dose of Lapatinib When Combined With Cranial Radiation in Patients With CNS Metastases From HER2-positive Breast Cancer.	1250 milligrams

SECONDARY outcome

Timeframe: 5 years

Progression Free Survival is the time from date of start of treatment to the date of the first documented progression or death due to any cause. If a patient has not progressed or died, progression free survival is censored at the time of last tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20 % increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=35 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Progression Free Survival	4.8 months Interval 0.0 to 58.3

SECONDARY outcome

Timeframe: 5 years

Population: 28 participants had measurable disease out of the 35 participants enrolled.

Objective Response Rate was defined using volumetric response as the following: Complete Response (CR) is the disappearance of all target lesions, stable/responsive non-target lesions, and no new lesions. Partial response (PR) is at least a 50% reduction in the sum of the target lesions, stable/responsive non-target lesions, and no new lesions. Stable Disease (SD) is neither CR PR or Progressive Disease (PD). And Progressive Disease (PD) is at least 40% increase in sum of target lesionsor the appearance of any new lesion \>=6mm in the longest dimension. If a patient progressed in a non-central nervous system(CNS) site first, died, or withdrew from the study for any reason after the first dose of drug was administered, and before a CR or PR in the central nervous system was determined, she was considered a CNS non-responder.

Outcome measures

Outcome measures
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=28 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Objective Response Rate in Central Nervous System Sites	79 percentage of participants Interval 59.0 to 92.0

SECONDARY outcome

Timeframe: 5 years

Outcome measures

Outcome measures
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=35 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Percentage of Participants Having Central Nervous System as the Site of the First Progression	23 percentage of participants

SECONDARY outcome

Timeframe: 5 years

Outcome measures

Outcome measures
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=35 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Percentage of Participants Having Non-Central Nervous System Sites as the Site of First Progression	46 percentage of participants

SECONDARY outcome

Timeframe: Participants were followed for an average of 3.8 years

Overall average length of participant survival after protocol initiation

Outcome measures

Outcome measures
Measure	Lapatinib,Whole Brain Radiation,Herceptin n=35 Participants Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Overall Survival	19 Months Interval 1.0 to 62.0

Adverse Events

Dose Level 2

Serious events: 8 serious events

Other events: 27 other events

Deaths: 0 deaths

Dose Level 1

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Level 3

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 2 n=27 participants at risk n=27 participants Maximum Tolerated Dose 1250 mg lapatinib daily	Dose Level 1 n=3 participants at risk n=3 participants 1000 mg lapatinib daily	Dose Level 3 n=5 participants at risk n=5 participants 1500 mg lapatinib daily
Respiratory, thoracic and mediastinal disorders Hypoxia	3.7% 1/27 • Number of events 1 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/3 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/5 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.
Respiratory, thoracic and mediastinal disorders Sinusitis	3.7% 1/27 • Number of events 1 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/3 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/5 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.
Gastrointestinal disorders Diarrhea	7.4% 2/27 • Number of events 2 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/3 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/5 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolus	7.4% 2/27 • Number of events 2 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/3 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/5 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.
Gastrointestinal disorders Vomiting	7.4% 2/27 • Number of events 2 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/3 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.	0.00% 0/5 • May 2007- December 2009 Serious Adverse Events include all Participants N=35. Non-serious Adverse Events also include all participants N=35.

Other adverse events

Additional Information

Nancy Lin, MD

Dana-Farber Cancer Institute

Phone: 617-632-2335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place