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Letrozole and Lapatinib Followed by Everolimus in Women With Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT01499160
Recruitment Status : Terminated (low accrual)
First Posted : December 26, 2011
Results First Posted : March 6, 2018
Last Update Posted : November 1, 2018
Sponsor:
Collaborators:
Novartis Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
Katherine Tkaczuk, University of Maryland, College Park

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Neoplasms
Endocrine Breast Diseases
Neoplasm Metastasis
Interventions Drug: letrozole
Drug: lapatinib
Drug: everolimus
Enrollment 7
Recruitment Details University Medical Centers and Hospital Based Oncology Programs recruited participants from July 2012 to December 2014.
Pre-assignment Details All 7 patients (2 pts were HER2+ and 5 pts were HER2-) started the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day.
Arm/Group Title Letrozole in Combination With Lapatinib Followed by Everolimus
Hide Arm/Group Description

Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue

In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus.

letrozole: Drug is are to be taken orally. 2.5 mg once daily

lapatinib: Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)

everolimus: Drug is to be taken orally. 5 mg once daily.

Period Title: Overall Study
Started 7
Completed [1] 5 [2]
Not Completed 2
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             1
[1]
number of who completed all study treatments
[2]

1 pt-withdrew consent

1pt-had cardiac toxicity

Arm/Group Title Letrozole in Combination With Lapatinib Followed by Everolimus
Hide Arm/Group Description

Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue

In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus.

letrozole: Drug is are to be taken orally. 2.5 mg once daily

lapatinib: Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)

everolimus: Drug is to be taken orally. 5 mg once daily.

Overall Number of Baseline Participants 7
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 7 participants
60
(50 to 71)
[1]
Measure Description: age is a continuous variable and is collected from patient's charts
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
Female
7
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 7 participants
7
 100.0%
1.Primary Outcome
Title Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib.
Hide Description

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, 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; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

Clinical benefit rate is defined as complete response+partial response+ stable disease. All participants will be treated with the combination of letrozole and lapatinib. Once the participant progresses on this regimen, the participant will be treated with everolimus, letrozole and lapatinib until they progress.

Time Frame From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient withdrew during cycle 1
Arm/Group Title Letrozole in Combination With Lapatinib Followed by Everolimus
Hide Arm/Group Description:

Group 1: HER2-positive in the tumor tissue-2 subjects Group 2: HER2 negative in the tumor tissue-5 subjects

In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus.

letrozole: Drug is are to be taken orally. 2.5 mg once daily

lapatinib: Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)

everolimus: Drug is to be taken orally. 5 mg once daily.

Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
2.Secondary Outcome
Title PROGRESSION FREE SURVIVAL TUMOR ASSESSMENT
Hide Description Patients treated with the combination of Letrozole and Lapatinib will provide tumor biopsy sample
Time Frame From date of study entry until 4 weeks after removal from study or until death (whichever occurs first) up to 24 months.
Hide Outcome Measure Data
Hide Analysis Population Description
data analysis was not conducted due to low sample (low accrual) and study closure
Arm/Group Title Letrozole in Combination With Lapatinib Followed by Everolimus
Hide Arm/Group Description:

Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue

In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus.

letrozole: Drug is are to be taken orally. 2.5 mg once daily

lapatinib: Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)

everolimus: Drug is to be taken orally. 5 mg once daily.

Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letrozole in Combination With Lapatinib Followed by Everolimus
Comments Not done due to low accrual
Type of Statistical Test Other
Comments Not done due to low accrual
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Not done due to low accrual
Method Not done due to low accrual
Comments Not done due to low accrual
Other Statistical Analysis Not done due to low accrual
Time Frame Adverse events including serious adverse events (SAEs) were collected from the start of study until 30 days after completion of last study drug dose on all study patients (7), but only 4 severe adverse events were noted as reported previously.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Letrozole in Combination With Lapatinib Followed by Everolimus
Hide Arm/Group Description

Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue

In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus.

letrozole: Drug is are to be taken orally. 2.5 mg once daily

lapatinib: Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)

everolimus: Drug is to be taken orally. 5 mg once daily.

All-Cause Mortality
Letrozole in Combination With Lapatinib Followed by Everolimus
Affected / at Risk (%)
Total   0/7 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Letrozole in Combination With Lapatinib Followed by Everolimus
Affected / at Risk (%) # Events
Total   4/7 (57.14%)    
Blood and lymphatic system disorders   
Decreased LVEF *  1/7 (14.29%)  1
Gastrointestinal disorders   
nausea *  1/7 (14.29%)  1
General disorders   
fatigue *  1/7 (14.29%)  1
Renal and urinary disorders   
rectal pain *  1/7 (14.29%)  1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Letrozole in Combination With Lapatinib Followed by Everolimus
Affected / at Risk (%) # Events
Total   7/7 (100.00%)    
Blood and lymphatic system disorders   
Anemia *  2/7 (28.57%)  2
Leucopenia *  1/7 (14.29%)  2
lymphedema *  1/7 (14.29%)  2
Lymphopenia *  1/7 (14.29%)  1
Ear and labyrinth disorders   
Otitis Externa *  1/7 (14.29%)  1
Endocrine disorders   
elevated ALT & AST *  5/7 (71.43%)  9
Eye disorders   
right eyelid swelling *  1/7 (14.29%)  1
Gastrointestinal disorders   
abdominal pain *  2/7 (28.57%)  2
Constipation *  1/7 (14.29%)  1
diarrhea *  5/7 (71.43%)  11
epigastric pain *  1/7 (14.29%)  1
nausea *  4/7 (57.14%)  6
General disorders   
dehydration *  1/7 (14.29%)  1
diaphoresis *  1/7 (14.29%)  1
dizziness *  2/7 (28.57%)  2
epistaxis *  1/7 (14.29%)  1
Fatigue *  3/7 (42.86%)  8
hair loss *  2/7 (28.57%)  2
hypertriglyceridemia *  2/7 (28.57%)  2
mouth ulcers *  1/7 (14.29%)  1
mucositis *  3/7 (42.86%)  6
numbness in toes *  1/7 (14.29%)  1
pain *  1/7 (14.29%)  1
right foot pain *  1/7 (14.29%)  1
right hip pain *  1/7 (14.29%)  1
right shoulder pain *  1/7 (14.29%)  1
righted sided pain *  1/7 (14.29%)  1
stomatitis *  1/7 (14.29%)  1
vomiting *  1/7 (14.29%)  1
weight gain *  1/7 (14.29%)  1
weight loss *  1/7 (14.29%)  1
Injury, poisoning and procedural complications   
accidental everolimus overdose *  1/7 (14.29%)  1
Metabolism and nutrition disorders   
anorexia *  2/7 (28.57%)  2
Musculoskeletal and connective tissue disorders   
arthralgias *  1/7 (14.29%)  1
Bone pain *  1/7 (14.29%)  1
Fracture fibula *  1/7 (14.29%)  1
hip pain *  2/7 (28.57%)  2
joint pain *  1/7 (14.29%)  1
myalgia *  1/7 (14.29%)  1
right back pain *  1/7 (14.29%)  1
Renal and urinary disorders   
UTI *  1/7 (14.29%)  1
Respiratory, thoracic and mediastinal disorders   
URI *  2/7 (28.57%)  2
Skin and subcutaneous tissue disorders   
rash *  5/7 (71.43%)  10
right toe cellulitis *  1/7 (14.29%)  1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michelle Medeiros
Organization: University of Maryland Baltimore Greenebaum Cancer Center
Phone: 410-328-1160
EMail: mmedeiros@umm.edu
Layout table for additonal information
Responsible Party: Katherine Tkaczuk, University of Maryland, College Park
ClinicalTrials.gov Identifier: NCT01499160     History of Changes
Other Study ID Numbers: HP-00040802; GCC 0901
GCC 0901 ( Other Identifier: University of Maryland Greenebaum Cancer Center )
First Submitted: December 14, 2011
First Posted: December 26, 2011
Results First Submitted: March 15, 2016
Results First Posted: March 6, 2018
Last Update Posted: November 1, 2018