Trial Outcomes & Findings for Letrozole and Lapatinib Followed by Everolimus in Women With Advanced Breast Cancer (NCT NCT01499160)

Last Updated: 2022-02-11

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

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

Results posted on

2022-02-11

Participant Flow

University Medical Centers and Hospital Based Oncology Programs recruited participants from July 2012 to December 2014.

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.

Participant milestones

Participant milestones
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus 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 Study STARTED	7
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus 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 Study Adverse Event	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus n=7 Participants 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.
Age, Continuous	60 years n=99 Participants
Sex: Female, Male Female	7 Participants n=99 Participants
Sex: Female, Male Male	0 Participants n=99 Participants
Region of Enrollment United States	7 Participants n=99 Participants

PRIMARY outcome

Timeframe: 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

Population: 1 patient withdrew during cycle 1

Outcome measures

Outcome measures
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus n=6 Participants 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.
Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib.	6 Participants

SECONDARY outcome

Timeframe: From date of study entry until 4 weeks after removal from study or until death (whichever occurs first) up to 24 months.

Population: data analysis was not conducted due to low sample (low accrual) and study closure

Patients treated with the combination of Letrozole and Lapatinib will provide tumor biopsy sample

Outcome measures

Outcome measures
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus n=6 Participants 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.
PROGRESSION FREE SURVIVAL TUMOR ASSESSMENT	6 Participants

Adverse Events

Letrozole in Combination With Lapatinib Followed by Everolimus

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus n=7 participants at risk 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.
Blood and lymphatic system disorders Decreased LVEF	14.3% 1/7 • Number of events 1 • 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.
General disorders fatigue	14.3% 1/7 • Number of events 1 • 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.
Gastrointestinal disorders nausea	14.3% 1/7 • Number of events 1 • 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.
Renal and urinary disorders rectal pain	14.3% 1/7 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	Letrozole in Combination With Lapatinib Followed by Everolimus n=7 participants at risk 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.
Gastrointestinal disorders abdominal pain	28.6% 2/7 • Number of events 2 • 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.
Injury, poisoning and procedural complications accidental everolimus overdose	14.3% 1/7 • Number of events 1 • 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.
Blood and lymphatic system disorders Anemia	28.6% 2/7 • Number of events 2 • 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.
Metabolism and nutrition disorders anorexia	28.6% 2/7 • Number of events 2 • 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.
Musculoskeletal and connective tissue disorders arthralgias	14.3% 1/7 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Bone pain	14.3% 1/7 • Number of events 1 • 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.
Gastrointestinal disorders Constipation	14.3% 1/7 • Number of events 1 • 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.
General disorders dehydration	14.3% 1/7 • Number of events 1 • 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.
General disorders diaphoresis	14.3% 1/7 • Number of events 1 • 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.
Gastrointestinal disorders diarrhea	71.4% 5/7 • Number of events 11 • 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.
General disorders dizziness	28.6% 2/7 • Number of events 2 • 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.
Endocrine disorders elevated ALT & AST	71.4% 5/7 • Number of events 9 • 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.
Gastrointestinal disorders epigastric pain	14.3% 1/7 • Number of events 1 • 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.
General disorders epistaxis	14.3% 1/7 • Number of events 1 • 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.
General disorders Fatigue	42.9% 3/7 • Number of events 8 • 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.
Musculoskeletal and connective tissue disorders Fracture fibula	14.3% 1/7 • Number of events 1 • 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.
General disorders hair loss	28.6% 2/7 • Number of events 2 • 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.
Musculoskeletal and connective tissue disorders hip pain	28.6% 2/7 • Number of events 2 • 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.
General disorders hypertriglyceridemia	28.6% 2/7 • Number of events 2 • 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.
Musculoskeletal and connective tissue disorders joint pain	14.3% 1/7 • Number of events 1 • 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.
Blood and lymphatic system disorders Leucopenia	14.3% 1/7 • Number of events 2 • 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.
Blood and lymphatic system disorders lymphedema	14.3% 1/7 • Number of events 2 • 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.
Blood and lymphatic system disorders Lymphopenia	14.3% 1/7 • Number of events 1 • 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.
General disorders mouth ulcers	14.3% 1/7 • Number of events 1 • 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.
General disorders mucositis	42.9% 3/7 • Number of events 6 • 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.
Musculoskeletal and connective tissue disorders myalgia	14.3% 1/7 • Number of events 1 • 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.
Gastrointestinal disorders nausea	57.1% 4/7 • Number of events 6 • 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.
General disorders numbness in toes	14.3% 1/7 • Number of events 1 • 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.
Ear and labyrinth disorders Otitis Externa	14.3% 1/7 • Number of events 1 • 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.
General disorders pain	14.3% 1/7 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders rash	71.4% 5/7 • Number of events 10 • 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.
Musculoskeletal and connective tissue disorders right back pain	14.3% 1/7 • Number of events 1 • 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.
Eye disorders right eyelid swelling	14.3% 1/7 • Number of events 1 • 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.
General disorders right foot pain	14.3% 1/7 • Number of events 1 • 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.
General disorders right hip pain	14.3% 1/7 • Number of events 1 • 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.
General disorders right shoulder pain	14.3% 1/7 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders right toe cellulitis	14.3% 1/7 • Number of events 1 • 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.
General disorders righted sided pain	14.3% 1/7 • Number of events 1 • 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.
General disorders stomatitis	14.3% 1/7 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders URI	28.6% 2/7 • Number of events 2 • 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.
Renal and urinary disorders UTI	14.3% 1/7 • Number of events 1 • 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.
General disorders vomiting	14.3% 1/7 • Number of events 1 • 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.
General disorders weight gain	14.3% 1/7 • Number of events 1 • 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.
General disorders weight loss	14.3% 1/7 • Number of events 1 • 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.

Additional Information

Michelle Medeiros

University of Maryland Baltimore Greenebaum Cancer Center

Phone: 410-328-1160

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place