Trial Outcomes & Findings for Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer (NCT NCT01873833)
NCT ID: NCT01873833
Last Updated: 2023-10-05
Results Overview
PFS was defined as duration of time from the first dose of study drug to the first documentation of Progressive Disease (PD) by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: \>=20% increase (\>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
From study entry to the date of first documented disease progression (assessed every 6 weeks) or death due to any cause, whichever came first, approximately 63 months.
Results posted on
2023-10-05
Participant Flow
The study began recruiting in July 2013 and ended May 2017. Subjects were recruited from Los Angeles County + University of Southern California (LAC+USC) Healthcare Network and the Keck Medical Center of USC, Norris Comprehensive Cancer Center in Los Angeles, California.
There were no pre-assignment criteria. All subjects were given the same treatment.
Participant milestones
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 Participants
Patients receive capecitabine by mouth (PO) everyday (QD), cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Status 0
|
4 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Status1
|
6 Participants
n=5 Participants
|
|
Breast cancer stage at diagnosis
II
|
5 Participants
n=5 Participants
|
|
Breast cancer stage at diagnosis
III
|
3 Participants
n=5 Participants
|
|
Breast cancer stage at diagnosis
IV
|
2 Participants
n=5 Participants
|
|
Cancer Histologic Type (from surgical excision)
Ductal Infiltrating Carcinoma
|
10 Participants
n=5 Participants
|
|
Cancer Histologic Type (from surgical excision)
Other
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From study entry to the date of first documented disease progression (assessed every 6 weeks) or death due to any cause, whichever came first, approximately 63 months.Population: All participants were included in the analysis. Statistical analysis was not performed.
PFS was defined as duration of time from the first dose of study drug to the first documentation of Progressive Disease (PD) by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: \>=20% increase (\>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.
Outcome measures
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 Participants
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Progression Free Survival (PFS)
|
13.7 months
Interval 2.6 to 16.6
|
SECONDARY outcome
Timeframe: From study entry until disease progression/recurrence (maximum duration: 351 weeks)Population: All patients were included in the analysis. Statistical analysis was not performed.
Overall response rate (ORR) is complete response (CR) + partial response (PR) recorded from study entry until disease progression based on RECIST v1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Outcome measures
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 Participants
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Response Rate (ORR)
|
4 Participants
|
SECONDARY outcome
Timeframe: From study entry until the date of the first documented disease progression of date of death whichever came first, assessed for approximately 351 weeksPopulation: All patients were included in the analysis. Statistical analysis was not performed.
Participants with a best response of CR, PR, or stable disease (SD) sustained for ≥24 weeks, as assessed using RECIST v1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to \<10 mm in short axis. PR: \>=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: \>=20% increase (\>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.
Outcome measures
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 Participants
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Clinical Benefit Rate (CBR)
|
7 Participants
|
SECONDARY outcome
Timeframe: From study entry until death from any cause or date of last contact (up to 70 months)Population: All enrolled patients were included. Statistical analysis was not performed.
OS is the duration from study entry to death. Participants last known to be alive are censored at date of last contact.
Outcome measures
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 Participants
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Survival (OS)
|
29.6 Months
Interval 11.8 to 81.9
|
SECONDARY outcome
Timeframe: ****Time Frame: Adverse events were collected from first dose of study treatment up to 30 days after last dose of treatment, up to 63 months (number or treatment given ranged from 2 cycles to 85 cycles).Population: All patients enrolled are included
Assessment based on CTCAE version 4.0 toxicity criteria. For the detailed list of adverse events see the adverse event module.
Outcome measures
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 Participants
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Participants With Any Adverse Events as a Measure of Safety and Tolerability
|
10 Participants
|
Adverse Events
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
Serious events: 5 serious events
Other events: 10 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 participants at risk
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
10047700 - Vomiting
|
30.0%
3/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
General disorders
10016256 - Fatigue
|
20.0%
2/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Infections and infestations
10034016 - Paronychia
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Investigations
10047900 - Weight loss
|
30.0%
3/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Metabolism and nutrition disorders
10020639 - Hyperglycemia
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Musculoskeletal and connective tissue disorders
10028411 - Myalgia
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Skin and subcutaneous tissue disorders
10054524 - Palmar-plantar erythrodysesthesia syndrome
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Immune system disorders
10002218 - Anaphylaxis
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
General disorders
Death NOS
|
50.0%
5/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
Other adverse events
| Measure |
Treatment (Chemotherapy, Lapatinib Ditosylate, Trastuzumab)
n=10 participants at risk
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
capecitabine: Given PO
cyclophosphamide: Given PO
lapatinib ditosylate: Given PO
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Blood and lymphatic system disorders
10002272 - Anemia
|
50.0%
5/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Cardiac disorders
10008481 - Chest pain - cardiac
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Ear and labyrinth disorders
10047340 - Vertigo
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Eye disorders
10047848 - Watering eyes
|
40.0%
4/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Gastrointestinal disorders
10000081 - Abdominal pain
|
90.0%
9/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
General disorders
10050068 - Edema limbs
|
100.0%
10/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Hepatobiliary disorders
10019805 - Hepatobiliary disorders - Other, specify
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Infections and infestations
Paronychia
|
30.0%
3/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Injury, poisoning and procedural complications
10006504 - Bruising
|
30.0%
3/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Investigations
10001551 - Alanine aminotransferase increased
|
70.0%
7/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Metabolism and nutrition disorders
10002646 - Anorexia
|
60.0%
6/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Musculoskeletal and connective tissue disorders
10003239 - Arthralgia
|
70.0%
7/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Nervous system disorders
10013911 - Dysgeusia
|
50.0%
5/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Psychiatric disorders
10002855 - Anxiety
|
50.0%
5/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Renal and urinary disorders
10038359 - Renal and urinary disorders - Other, specify
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Reproductive system and breast disorders
10046937 - Vaginal pain
|
10.0%
1/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Respiratory, thoracic and mediastinal disorders
10011224 - Cough
|
70.0%
7/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Skin and subcutaneous tissue disorders
10037087 - Pruritus
|
100.0%
10/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
|
Vascular disorders
10020772 - Hypertension
|
40.0%
4/10 • Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose, up to 63 months.
Adverse events (AE) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
|
Additional Information
Victoria Soto, Regulatory Administrator
USC Norris Comprehensive Cancer Center
Phone: 323-865-0432
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place