Trial Outcomes & Findings for Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer (NCT NCT00479856)

NCT ID: NCT00479856

Last Updated: 2012-06-05

Results Overview

Overall tumor response is defined as the percentage of participants with a confirmed complete or partial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as the disappearance of all target lesions. CR could only be declared if all target and non-target lesions had disappeared. Partial response (PR) is defined as a decrease of 30% or greater in the sum of the longest diameter of target lesions.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 wks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, of other reason)
• Results posted on: 2012-06-05

Participant Flow

Participant milestones

Measure	Lapatinib + Chemotherapy 1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Overall Study STARTED	9
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Lapatinib + Chemotherapy 1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1
Overall Study Physician Decision	1

Baseline Characteristics

Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer

Baseline characteristics by cohort

Measure	Lapatinib + Chemotherapy n=9 Participants 1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Age Continuous	61.9 years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White	7 participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	1 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants

PRIMARY outcome

Timeframe: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 wks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, of other reason)

Population: All Treated Subjects (ATS) Population: all participants who received at least one dose of study treatment

Overall tumor response is defined as the percentage of participants with a confirmed complete or partial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as the disappearance of all target lesions. CR could only be declared if all target and non-target lesions had disappeared. Partial response (PR) is defined as a decrease of 30% or greater in the sum of the longest diameter of target lesions.

Outcome measures

Measure

Lapatinib + Chemotherapy n=9 Participants 1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle

Overall Tumor Response

33.3 percentage of participants

SECONDARY outcome

Timeframe: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)

Population: Due to the low incidence of relapse and hence the difficulty in identifying eligible par., the study was terminated with only 9 out of the 45 planned par. enrolled. As there were too few par. to derive statistically meaningful conclusions, only the primary endpoint was evaluated.

CB is defined as the percentage of participants (par.) with either a confirmed CR or PR or stable disease (SD) for at least 24 weeks. SD is defined as small changes that do not meet criteria for CR, PR, or Progressive Disease (defined as at least a 20% increase in the sum of the longest diameter of target lesions).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: time from first documented evidence of CR or PR until the first documented sign of disease progression or death (approximately 95 weeks)

Population: Due to the low incidence of relapse and hence the difficulty in identifying eligible participants, the study was terminated with only 9 out of the 45 planned participants enrolled. As there were too few participants to derive statistically meaningful conclusions, only the primary endpoint was evaluated.

For the subset of participants with a confirmed CR or PR, duration of response was measured as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: start of treatment until first documented evidence of CR or PR (approximately 95 weeks)

Population: Due to the low incidence of relapse and hence the difficulty in identifying eligible participants, the study was terminated with only 9 out of the 45 planned participants enrolled. As there were too few participants to derive statistically meaningful conclusions, only the primary endpoint was evaluated.

TTR is defined as the time from the start of treatment until the first documented evidence of PR or CR (whichever status was recorded first). When tumor response was confirmed at a repeat assessment, the TTR was taken to be the first time that the response was observed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks); dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)

Population: Due to the low incidence of relapse and hence the difficulty in identifying eligible participants, the study was terminated with only 9 out of the 45 planned participants enrolled. As there were too few participants to derive statistically meaningful conclusions, only the primary endpoint of overall response rate was evaluated.

The time from the start of treatment until the earliest date of disease progression or death due to any cause was measured.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through End of Treatment, or discontinuation of study therapy (approximately 95 weeks); from the first dose of lapatinib until 5 days after the last dose of lapatinib

Qualitative and quantitative toxicities associated with the combination of capecitabine, docetaxel, or nab-paclitaxel and lapatinib were measured. Data are presented as serious adverse events (SAEs) and adverse events (AEs). See the SAE/AE section of the results record for data.

Outcome measures

Outcome data not reported

Adverse Events

Lapatinib + Chemotherapy

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lapatinib + Chemotherapy n=9 participants at risk 1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Gastrointestinal disorders Small intestinal obstruction	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Small intestinal perforation	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.

Other adverse events

Measure	Lapatinib + Chemotherapy n=9 participants at risk 1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Gastrointestinal disorders Diarrhoea	77.8% 7/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
General disorders Fatigue	77.8% 7/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Nausea	66.7% 6/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Skin and subcutaneous tissue disorders Palmar plantar erythrodysaesthesia	55.6% 5/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Skin and subcutaneous tissue disorders Rash	44.4% 4/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Vomiting	44.4% 4/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Constipation	33.3% 3/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Blood and lymphatic system disorders Anaemia	33.3% 3/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Metabolism and nutrition disorders Hypokalaemia	33.3% 3/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Dyspesia	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
General disorders Mucosal inflammation	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Infections and infestations Urinary tract infection	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Investigations Aspartatate aminotransferase increased	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Metabolism and nutrition disorders Hypocalcaemia	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Musculoskeletal and connective tissue disorders Pain in extremity	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Nervous system disorders Headache	22.2% 2/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Haemorrhoids	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Rectal haemorrhage	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Small intestinal obstruction	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Gastrointestinal disorders Small intestinal perforation	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
General disorders Chest pain	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
General disorders Feeling cold	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
General disorders Local swelling	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
General disorders Pain	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Skin and subcutaneous tissue disorders Skin chapped	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Skin and subcutaneous tissue disorders Skin discolouration	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Skin and subcutaneous tissue disorders Skin exfoliation	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Blood and lymphatic system disorders Leukopenia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Blood and lymphatic system disorders Lymphadenopathy	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Blood and lymphatic system disorders Neutropenia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Infections and infestations Paronychia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Infections and infestations Periorbital cellulitis	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Infections and infestations Vulvovaginal mycotic infection	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Investigations Alanine aminotransferase increased	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Investigations Weight decreased	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Metabolism and nutrition disorders Hyperlipidaemia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Metabolism and nutrition disorders Hypoalbuminaemia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Metabolism and nutrition disorders Hypoglycaemia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Musculoskeletal and connective tissue disorders Back pain	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Nervous system disorders Dysgeusia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Nervous system disorders Neuropathy peripheral	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Reproductive system and breast disorders Menorrhagia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Reproductive system and breast disorders Vulvovaginal dryness	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Eye disorders Conjunctivitis	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Psychiatric disorders Insomnia	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Renal and urinary disorders Proteinuria	11.1% 1/9 • Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER