Trial Outcomes & Findings for Phase II Trial to Validate Markers for a Response Evaluation of a Combined Therapy in Patients With HER2+ Breast Cancer (NCT NCT01891357)
NCT ID: NCT01891357
Last Updated: 2019-09-17
Results Overview
pCR was defined at the time of surgery and measured by size of residual tumor, proportion of vital cells within invasive carcinoma, number of positive lymph nodes (ypN) and size of the largest lymph node metastasis and ductal carcinoma in situ (ypT). pCR is defined as ypT0/is, ypN0. Further exploratory pCR definitions were ypT0, ypN0 (total pCR) and ypT0/is (near pCR).
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
64 participants
Primary outcome timeframe
Average of 16 weeks
Results posted on
2019-09-17
Participant Flow
Patients should only have been registered for the study, if final results of screening evaluations were available and all inclusion/exclusion criteria met. This was not true for 3 patients. Patients should not have been registered due to distant metastasis. These patients were classified as screening failures and withdrawn from the study.
Participant milestones
| Measure |
Paclitaxel + Lapatinib + Trastuzumab
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Biopsy before and after three weeks of study treatment: Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxel
lapatinib
trastuzumab
|
|---|---|
|
Overall Study
STARTED
|
64
|
|
Overall Study
COMPLETED
|
61
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Paclitaxel + Lapatinib + Trastuzumab
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Biopsy before and after three weeks of study treatment: Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxel
lapatinib
trastuzumab
|
|---|---|
|
Overall Study
Protocol Violation
|
3
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Paclitaxel + Lapatinib + Trastuzumab
n=61 Participants
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Biopsy before and after three weeks of study treatment: Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxel
lapatinib
trastuzumab
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=61 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
51 Participants
n=61 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=61 Participants
|
|
Age, Continuous
|
50.3 years
STANDARD_DEVIATION 10.8 • n=61 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=61 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=61 Participants
|
|
Region of Enrollment
Germany
|
61 participants
n=61 Participants
|
PRIMARY outcome
Timeframe: Average of 16 weeksPopulation: Measurement of pCR: at time of surgery, measured by size of residual tumor, proportion of vital cells per invasive carcinoma, number of positive lymph nodes (ypN), size of largest lymph node metastasis, ductal carcinoma in situ (ypT). Definition of pCR: ypT0/is, ypN0. Exploratory pCR definition: ypT0, ypN0 (total pCR), ypT0/is (near pCR).
pCR was defined at the time of surgery and measured by size of residual tumor, proportion of vital cells within invasive carcinoma, number of positive lymph nodes (ypN) and size of the largest lymph node metastasis and ductal carcinoma in situ (ypT). pCR is defined as ypT0/is, ypN0. Further exploratory pCR definitions were ypT0, ypN0 (total pCR) and ypT0/is (near pCR).
Outcome measures
| Measure |
Paclitaxel + Lapatinib + Trastuzumab
n=61 Participants
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Biopsy before and after three weeks of study treatment: Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxel
lapatinib
trastuzumab
|
|---|---|
|
Pathological Complete Response (pCR)
ypT0, ypN0
|
19 Participants
|
|
Pathological Complete Response (pCR)
ypT0/is
|
27 Participants
|
|
Pathological Complete Response (pCR)
ypT0/is, ypN0
|
25 Participants
|
SECONDARY outcome
Timeframe: 5-year survivalPopulation: Data were not collected and the outcome cannot be reported
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5-year survivalPopulation: Data were not collected and the outcome cannot be reported
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: One week before and after three weeks of treatmentPopulation: Data were not collected and the outcome cannot be reported
Proliferation Ki-67, Aurora A Kinase (STK15), survivin, Myb-related protein B (MYBL2),Cyclin B1 and apoptosis genes Bcl2, Epidermal Growth Factor-like 2 (SCUBE2), cleaved caspase C3 will be assessed in the samples from diagnostic and sequential biopsy.
Outcome measures
Outcome data not reported
Adverse Events
Paclitaxel + Lapatinib + Trastuzumab
Serious events: 16 serious events
Other events: 59 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Paclitaxel + Lapatinib + Trastuzumab
n=61 participants at risk
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Biopsy before and after three weeks of study treatment: Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxel
lapatinib
trastuzumab
|
|---|---|
|
Psychiatric disorders
Death
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Psychiatric disorders
anxiety
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Cholecystitis
|
1.6%
1/61 • Number of events 2 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Decreased appetite
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Renal and urinary disorders
Dehydration
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Vascular disorders
Device related thrombosis
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Gastrointestinal disorders
diarrhoea
|
4.9%
3/61 • Number of events 3 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
General disorders
Fatigue
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
hypokaleamia
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
impaired healing
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Mucosal Inflammation
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Eye disorders
Ophthalmic herpes simplex
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Infections and infestations
Pneumonia
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Infections and infestations
septic shock
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Subcutaneous abscess
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Cardiac disorders
Syncope
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Renal and urinary disorders
Urinary tract infection
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Renal and urinary disorders
Urosepsis
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
Other adverse events
| Measure |
Paclitaxel + Lapatinib + Trastuzumab
n=61 participants at risk
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Biopsy before and after three weeks of study treatment: Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxel
lapatinib
trastuzumab
|
|---|---|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
34.4%
21/61 • Number of events 21 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Cardiac disorders
Cardiac disorders
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders
|
4.9%
3/61 • Number of events 3 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Eye disorders
Eye disorders
|
8.2%
5/61 • Number of events 5 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
96.7%
59/61 • Number of events 133 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
General disorders
General disorders and administration site conditions
|
86.9%
53/61 • Number of events 53 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
3.3%
2/61 • Number of events 2 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Immune system disorders
Immune system disorders
|
8.2%
5/61 • Number of events 5 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Infections and infestations
Infections and infestations
|
49.2%
30/61 • Number of events 30 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
6.6%
4/61 • Number of events 4 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Investigations
Investigations
|
45.9%
28/61 • Number of events 28 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Metabolism and nMetabolism and nutrition disordersutrition disorders
|
16.4%
10/61 • Number of events 10 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
19.7%
12/61 • Number of events 12 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Nervous system disorders
Nervous system disorders
|
96.7%
59/61 • Number of events 66 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Psychiatric disorders
Psychiatric disorders
|
24.6%
15/61 • Number of events 15 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Renal and urinary disorders
Renal and urinary disorders
|
3.3%
2/61 • Number of events 2 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
1.6%
1/61 • Number of events 1 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
50.8%
31/61 • Number of events 31 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
96.7%
59/61 • Number of events 93 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
|
Vascular disorders
Vascular disorders
|
23.0%
14/61 • Number of events 14 • AE collection from signature of ICF until end of study per patient, up to 3 years.
Safety population for analysis of toxicities, comprised of 61 patients who were allocated to intervention and received at least one dose of study treatment.
|
Additional Information
Anja Braschoss, Consultant Clinical Research and Medical Writing
on behalf of Westdeutsche Studiengruppe GmbH
Phone: 0049-176-82119153
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60