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Anti-PD-1 Monoclonal Antibody in Advanced, Trastuzumab-resistant, HER2-positive Breast Cancer (PANACEA)

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ClinicalTrials.gov Identifier: NCT02129556
Recruitment Status : Completed
First Posted : May 2, 2014
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
Breast International Group
Information provided by (Responsible Party):
International Breast Cancer Study Group

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Intervention Drug: MK-3475
Enrollment 58
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase Ib 2 mg/kg Phase Ib 10 mg/kg Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. In the Phase Ib portion of the trial, two weight-based doses of MK-3475 were specified in the dose escalation (2 mg/kg and 10 mg/kg). HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. In the Phase Ib portion of the trial, two weight-based doses of MK-3475 were specified in the dose escalation (2 mg/kg and 10 mg/kg). HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. The Phase II portion of the trial used a flat dose of 200 mg of MK-3475 based on emerging data from the sponsor. HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. The Phase II portion of the trial used a flat dose of 200 mg of MK-3475 based on emerging data from the sponsor.
Period Title: Overall Study
Started 3 3 40 12
Completed 3 3 37 12
Not Completed 0 0 3 0
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1- Total
Hide Arm/Group Description HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy Total of all reporting groups
Overall Number of Baseline Participants 6 40 12 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 40 participants 12 participants 58 participants
48  (9.5) 51.2  (10.4) 54.5  (5.2) 51.5  (9.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 40 participants 12 participants 58 participants
Female
6
 100.0%
40
 100.0%
12
 100.0%
58
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 40 participants 12 participants 58 participants
Caucasian
4
  66.7%
30
  75.0%
8
  66.7%
42
  72.4%
Asian
0
   0.0%
2
   5.0%
1
   8.3%
3
   5.2%
Other
0
   0.0%
1
   2.5%
0
   0.0%
1
   1.7%
Missing
2
  33.3%
7
  17.5%
3
  25.0%
12
  20.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 40 participants 12 participants 58 participants
Austria
0
   0.0%
0
   0.0%
1
   8.3%
1
   1.7%
Belgium
0
   0.0%
6
  15.0%
3
  25.0%
9
  15.5%
Italy
0
   0.0%
6
  15.0%
1
   8.3%
7
  12.1%
Australia
4
  66.7%
13
  32.5%
4
  33.3%
21
  36.2%
France
2
  33.3%
15
  37.5%
3
  25.0%
20
  34.5%
1.Primary Outcome
Title Dose-Limiting Toxicity (DLT) of MK-3475 in Combination With Trastuzumab
Hide Description

Determination of dose-limiting toxicity (DLT) which is defined as an adverse event or abnormal laboratory value assessed as suspected to be trial treatment related (possible, probable or definite) and unrelated to disease or disease progression. Toxicities and lab values will be graded according to the NCI CTCAE (v4.0).

  1. Any grade-3 or greater non-hematological adverse event lasting at least one week;
  2. Any grade-4 hematological toxicity; or,
  3. Any adverse event resulting in a delay starting cycle 2 of more than 14 days.
Time Frame Within the first 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled during phase Ib portion, a patient receiving one or more doses of MK-3475 and trastuzumab is considered evaluable.
Arm/Group Title Phase Ib 2 mg/kg Phase Ib 10 mg/kg
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 3 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description Confirmed CR or PR as best overall response. At the time of each restaging, patients will be classified as achieving complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or non-evaluable for response according to RECIST (Version 1.1) criteria.
Time Frame Clinical and radiological tumor assessment will be performed by CT scan or MRI at baseline, at weeks 12, 18 and 24, then every 12 weeks until progression, or 24 weeks after stop of treatment if before progression.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase Ib were combined when reporting clinical measures for secondary outcomes and adverse events, for stronger response rates.
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 6 40 12
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.17
(0.01 to 0.58)
0.15
(0.07 to 0.29)
0.00
(0.00 to 0.18)
3.Secondary Outcome
Title Duration of Response (DoR)
Hide Description Duration of response (DoR) is defined among patients with objective response (confirmed CR or PR as best overall response) as the interval between dates of first documentation of objective response and first documentation of progressive disease. In the absence of documented progressive disease, follow-up will be censored at date of last disease assessment.
Time Frame From date of first documentation of objective response until first documentation of progressive disease, up to 24 weeks after stop of treatment (=30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who achieved objective response
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase Ib were combined when reporting clinical measures for secondary outcomes and adverse events, for stronger response rates.
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 1 6 0
Median (90% Confidence Interval)
Unit of Measure: months
23.1
3.5
(2.7 to 999999)
4.Secondary Outcome
Title Time to Progression (TTP)
Hide Description Time to progression (TTP) defined as the interval between the dates of the start of trial treatment and first documentation of progressive disease. In the absence of documented progressive disease, follow-up will be censored at date of last disease assessment
Time Frame From the first trial treatment until first documentation of progressive disease up to 24 weeks after stop of treatment (=30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase Ib were combined when reporting clinical measures for secondary outcomes and adverse events, for stronger response rates.
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 6 40 12
Median (90% Confidence Interval)
Unit of Measure: months
2.5
(1.1 to 2.7)
2.7
(2.6 to 4.9)
2.5
(1.4 to 999999)
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description The proportion of patients with best confirmed RECIST response of CR, PR, or duration of SD of at least 24 weeks (measured from first dose of trial treatment).
Time Frame From the start of trial treatment until confirmed CR, PR, or SD lasting for 24 weeks or longer
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase Ib were combined when reporting clinical measures for secondary outcomes and adverse events, for stronger response rates.
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 6 40 12
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.17
(0.01 to 0.58)
0.25
(0.14 to 0.39)
0.00
(0.00 to 0.18)
6.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description The interval between the dates of the first dose of trial treatment until first documentation of disease progression or death, whichever occurs first. Patients with new non-breast cancer malignancy must continue to be followed for progression of the original breast cancer. For patients without progression, follow-up is censored at the date of last disease assessment without progression, unless death occurs within 12 weeks following the date last known progression-free, in which case the death will be counted as a PFS event.
Time Frame From the date of first treatment dose until documented disease progression or death from any cause. whichever occur first, assessed up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase Ib were combined when reporting clinical measures for secondary outcomes and adverse events, for stronger response rates.
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 6 40 12
Median (90% Confidence Interval)
Unit of Measure: months
2.5
(1.1 to 2.7)
2.7
(2.6 to 4.0)
2.5
(1.4 to 2.7)
7.Secondary Outcome
Title Overall Survival (OS) at 12 Months
Hide Description OS is defined as the time from the first dose of trial treatment to death from any cause. For patients who are lost to follow-up or who have no documentation of death at the time of final analysis, follow-up is censored at the date of last assessment of vital status. OS at 12 months by Kaplan-Meier estimates.
Time Frame Time from start of trial treatment to death from any cause, assessed up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase Ib Phase II PD-L1+ Phase II PD-L1-
Hide Arm/Group Description:
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase Ib were combined when reporting clinical measures for secondary outcomes and adverse events, for stronger response rates.
HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
HER2-positive, PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy
Overall Number of Participants Analyzed 6 40 12
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.67
(0.27 to .88)
.65
(.50 to .76)
.12
(.01 to .36)
Time Frame From the date of signature of informed consent until 30 days after all treatment discontinuation, regardless of whether it was considered related to a medication. AEs were to be reported at the end of every treatment cycle, at the End-of-Treatment visit, and up to 30 days after cessation of trial treatment. Serious adverse event and pregnancy data were to be collected for 90 days following the end of treatment.
Adverse Event Reporting Description Any grade of any observed AE was to be reported on the AE form. There were no specifications of targeted AEs. Symptoms of the targeted cancer were not to be reported as AEs. AEs were categorized and graded according to CTCAE V4.
 
Arm/Group Title Phase Ib Phase II (PD-L1+ and PD-L1-)
Hide Arm/Group Description HER2-positive, PD-L1 expressing, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. All 6 patients in Phase I were combined when reporting clinical measures for secondary outcomes adverse events for stronger response rates. HER2-positive, PD-L1 expressing or PD-L1 negative, unresectable loco-regional or metastatic breast carcinoma that progressed on prior trastuzumab-based therapy. For adverse events, Phase II cohorts were combined since PD-L1 status does not affect toxicity.
All-Cause Mortality
Phase Ib Phase II (PD-L1+ and PD-L1-)
Affected / at Risk (%) Affected / at Risk (%)
Total   4/6 (66.67%)      25/52 (48.08%)    
Show Serious Adverse Events Hide Serious Adverse Events
Phase Ib Phase II (PD-L1+ and PD-L1-)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/6 (66.67%)      25/52 (48.08%)    
Blood and lymphatic system disorders     
Anemia   0/6 (0.00%)  1/52 (1.92%)  1
Cardiac disorders     
Takotsubo cardiomyopathy   1/6 (16.67%)  2 0/52 (0.00%)  0
Pericardial effusion   0/6 (0.00%)  2/52 (3.85%)  2
Ear and labyrinth disorders     
Vertigo   1/6 (16.67%)  1 0/52 (0.00%)  0
Eye disorders     
Retinal vein occlusion   0/6 (0.00%)  1/52 (1.92%)  1
Gastrointestinal disorders     
Gastroenteritis   1/6 (16.67%)  1 0/52 (0.00%)  0
Vomiting   1/6 (16.67%)  1 0/52 (0.00%)  0
Diarrhea   0/6 (0.00%)  1/52 (1.92%)  1
General disorders     
Death   2/6 (33.33%)  2 9/52 (17.31%)  9
Hepatobiliary disorders     
Bile duct dilatation   0/6 (0.00%)  1/52 (1.92%)  1
Hepatic hemorrhage   0/6 (0.00%)  1/52 (1.92%)  1
Drug-induced liver injury   0/6 (0.00%)  1/52 (1.92%)  1
Immune system disorders     
Lambert-Eaton syndrome   0/6 (0.00%)  1/52 (1.92%)  1
Autoimmune hepatitis   0/6 (0.00%)  1/52 (1.92%)  1
Infections and infestations     
Catheter-related infection   0/6 (0.00%)  1/52 (1.92%)  1
Sepsis   0/6 (0.00%)  1/52 (1.92%)  1
Investigations     
GGT increased   0/6 (0.00%)  1/52 (1.92%)  1
Musculoskeletal and connective tissue disorders     
Shoulder pain   1/6 (16.67%)  1 0/52 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Glioblastoma multiforme   0/6 (0.00%)  1/52 (1.92%)  1
Nervous system disorders     
CNS metastases   1/6 (16.67%)  1 0/52 (0.00%)  0
Paresthesia   0/6 (0.00%)  1/52 (1.92%)  1
Neurological paresis   0/6 (0.00%)  1/52 (1.92%)  1
Aphasia   0/6 (0.00%)  1/52 (1.92%)  1
Psychiatric disorders     
Cognitive disturbance   0/6 (0.00%)  1/52 (1.92%)  1
Renal and urinary disorders     
Acute renal impairment   0/6 (0.00%)  1/52 (1.92%)  1
Reproductive system and breast disorders     
Disease progression   2/6 (33.33%)  2 6/52 (11.54%)  6
Breast infection   0/6 (0.00%)  1/52 (1.92%)  1
Respiratory, thoracic and mediastinal disorders     
Upper respiratory infection   0/6 (0.00%)  2/52 (3.85%)  2
Plural effusion   0/6 (0.00%)  1/52 (1.92%)  1
Pneumonitis   0/6 (0.00%)  3/52 (5.77%)  3
Dyspnea   0/6 (0.00%)  3/52 (5.77%)  3
Pulmonary embolism   0/6 (0.00%)  1/52 (1.92%)  1
Skin and subcutaneous tissue disorders     
Rash   0/6 (0.00%)  1/52 (1.92%)  1
Vascular disorders     
Intracranial hypertension   0/6 (0.00%)  1/52 (1.92%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase Ib Phase II (PD-L1+ and PD-L1-)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      50/52 (96.15%)    
Blood and lymphatic system disorders     
Anemia   4/6 (66.67%)  6 8/52 (15.38%)  8
Fever   0/6 (0.00%)  0 1/52 (1.92%)  1
Lymph node pain   0/6 (0.00%)  0 1/52 (1.92%)  1
Reactive thrombocytosis   0/6 (0.00%)  0 1/52 (1.92%)  1
Cardiac disorders     
Pericardial effusion   0/6 (0.00%)  0 1/52 (1.92%)  1
Sinus tachycardia   0/6 (0.00%)  0 1/52 (1.92%)  1
Takotsubo cardiomyopathy   1/6 (16.67%)  2 0/52 (0.00%)  0
Ear and labyrinth disorders     
Ear pain   0/6 (0.00%)  0 1/52 (1.92%)  1
Hearing impaired   1/6 (16.67%)  1 0/52 (0.00%)  0
Vertigo   1/6 (16.67%)  3 2/52 (3.85%)  3
Endocrine disorders     
Hyperthyroidism   1/6 (16.67%)  1 1/52 (1.92%)  1
Hypothyroidism   1/6 (16.67%)  1 2/52 (3.85%)  2
Eye disorders     
Dry eye   0/6 (0.00%)  0 2/52 (3.85%)  2
Retinal vascular disorder   0/6 (0.00%)  0 1/52 (1.92%)  1
Visual field defect left lower quadrants   0/6 (0.00%)  0 1/52 (1.92%)  1
Gastrointestinal disorders     
Abdominal pain   0/6 (0.00%)  0 2/52 (3.85%)  3
Abdominal pain, intermittent   0/6 (0.00%)  0 1/52 (1.92%)  1
Colitis   0/6 (0.00%)  0 1/52 (1.92%)  1
Constipation   0/6 (0.00%)  0 5/52 (9.62%)  6
Diarrhea   2/6 (33.33%)  5 9/52 (17.31%)  11
Dry mouth   1/6 (16.67%)  1 2/52 (3.85%)  2
Gastritis   1/6 (16.67%)  1 1/52 (1.92%)  1
Gastroenteritis   1/6 (16.67%)  1 0/52 (0.00%)  0
Gastroesophageal reflux disease   0/6 (0.00%)  0 2/52 (3.85%)  2
Gastrointestinal pain   0/6 (0.00%)  0 1/52 (1.92%)  1
Mucositis oral   0/6 (0.00%)  0 3/52 (5.77%)  3
Nausea   1/6 (16.67%)  2 11/52 (21.15%)  14
Nausea with weight loss   1/6 (16.67%)  1 0/52 (0.00%)  0
Tongue mycosis   0/6 (0.00%)  0 1/52 (1.92%)  1
Vomiting   2/6 (33.33%)  2 3/52 (5.77%)  4
General disorders     
Anemia   0/6 (0.00%)  0 1/52 (1.92%)  1
Asthenia   0/6 (0.00%)  0 1/52 (1.92%)  1
Diaphoresis   0/6 (0.00%)  0 1/52 (1.92%)  1
Edema limbs   0/6 (0.00%)  0 4/52 (7.69%)  4
Edema trunk   0/6 (0.00%)  0 1/52 (1.92%)  1
Fatigue   3/6 (50.00%)  4 16/52 (30.77%)  23
Fever   1/6 (16.67%)  1 3/52 (5.77%)  5
Flu-like symptoms   0/6 (0.00%)  0 5/52 (9.62%)  5
Hoarseness   0/6 (0.00%)  0 1/52 (1.92%)  1
Infusion related reaction   0/6 (0.00%)  0 1/52 (1.92%)  1
Left breast tumour bleeding   0/6 (0.00%)  0 1/52 (1.92%)  1
Localized edema   1/6 (16.67%)  1 0/52 (0.00%)  0
Malaise   0/6 (0.00%)  0 1/52 (1.92%)  1
Non-cardiac chest pain   0/6 (0.00%)  0 2/52 (3.85%)  4
Pain   0/6 (0.00%)  0 6/52 (11.54%)  10
Hepatobiliary disorders     
Bile duct dilatation   0/6 (0.00%)  0 1/52 (1.92%)  2
Immune system disorders     
Autoimmune disorder   0/6 (0.00%)  0 1/52 (1.92%)  1
Infections and infestations     
Bronchial infection   0/6 (0.00%)  0 3/52 (5.77%)  3
Catheter-related infection   1/6 (16.67%)  1 1/52 (1.92%)  1
Dental   0/6 (0.00%)  0 1/52 (1.92%)  1
Esophageal infection   0/6 (0.00%)  0 1/52 (1.92%)  1
Laryngitis   0/6 (0.00%)  0 1/52 (1.92%)  1
Pharyngitis   0/6 (0.00%)  0 2/52 (3.85%)  4
Rhinitis infective   0/6 (0.00%)  0 3/52 (5.77%)  4
Sepsis   0/6 (0.00%)  0 1/52 (1.92%)  1
Sinusitis   1/6 (16.67%)  1 1/52 (1.92%)  1
Skin infection   1/6 (16.67%)  1 1/52 (1.92%)  1
Upper respiratory infection   2/6 (33.33%)  4 2/52 (3.85%)  3
Urinary tract infection   1/6 (16.67%)  1 1/52 (1.92%)  3
Yeasts in the stool   0/6 (0.00%)  0 1/52 (1.92%)  1
Investigations     
Alanine aminotransferase increased   1/6 (16.67%)  1 4/52 (7.69%)  4
Alkaline phosphatase increased   0/6 (0.00%)  0 3/52 (5.77%)  4
Aspartate aminotransferase increased   0/6 (0.00%)  0 3/52 (5.77%)  4
Blood bilirubin increased   0/6 (0.00%)  0 1/52 (1.92%)  3
Drug induced liver injury   0/6 (0.00%)  0 1/52 (1.92%)  1
Ggt increased   0/6 (0.00%)  0 5/52 (9.62%)  11
Hypercalcemia   0/6 (0.00%)  0 1/52 (1.92%)  1
Leucocyte count decreased   0/6 (0.00%)  0 1/52 (1.92%)  1
Lipase increased   0/6 (0.00%)  0 3/52 (5.77%)  6
Lymphocyte count decreased   1/6 (16.67%)  1 1/52 (1.92%)  1
Neutrophil count decreased   0/6 (0.00%)  0 2/52 (3.85%)  2
Serum amylase increased   0/6 (0.00%)  0 3/52 (5.77%)  3
Weight loss   0/6 (0.00%)  0 4/52 (7.69%)  4
White blood cell decreased   0/6 (0.00%)  0 1/52 (1.92%)  1
Metabolism and nutrition disorders     
Anorexia   0/6 (0.00%)  0 4/52 (7.69%)  4
Hypercalcemia   0/6 (0.00%)  0 3/52 (5.77%)  3
Hyperglycemia   0/6 (0.00%)  0 1/52 (1.92%)  1
Hyperkalemia   0/6 (0.00%)  0 3/52 (5.77%)  3
Hyperuricemia   0/6 (0.00%)  0 1/52 (1.92%)  1
Hypoalbuminemia   1/6 (16.67%)  1 2/52 (3.85%)  3
Hypocalcemia   1/6 (16.67%)  1 1/52 (1.92%)  1
Hypokalemia   0/6 (0.00%)  0 1/52 (1.92%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia   2/6 (33.33%)  3 6/52 (11.54%)  6
Back pain   0/6 (0.00%)  0 3/52 (5.77%)  5
Bone pain   0/6 (0.00%)  0 2/52 (3.85%)  2
Buttock pain   0/6 (0.00%)  0 1/52 (1.92%)  1
Shoulder pain   2/6 (33.33%)  2 0/52 (0.00%)  0
Myalgia   2/6 (33.33%)  2 4/52 (7.69%)  4
Neck pain   0/6 (0.00%)  0 1/52 (1.92%)  1
Pain   0/6 (0.00%)  0 1/52 (1.92%)  1
Pain in extremity   0/6 (0.00%)  0 1/52 (1.92%)  1
Stiffness   0/6 (0.00%)  0 1/52 (1.92%)  1
Nervous system disorders     
Aphasia   0/6 (0.00%)  0 1/52 (1.92%)  1
Aphonia   0/6 (0.00%)  0 1/52 (1.92%)  2
Ataxia   0/6 (0.00%)  0 1/52 (1.92%)  1
Balance disorder   0/6 (0.00%)  0 1/52 (1.92%)  1
Cognitive disturbance   0/6 (0.00%)  0 1/52 (1.92%)  1
Dizziness   0/6 (0.00%)  0 2/52 (3.85%)  2
Dysesthesia   0/6 (0.00%)  0 1/52 (1.92%)  1
Dysgeusia   0/6 (0.00%)  0 1/52 (1.92%)  1
Dysphasia   0/6 (0.00%)  0 1/52 (1.92%)  1
Headache   2/6 (33.33%)  3 8/52 (15.38%)  15
Loss of hand motor traction   1/6 (16.67%)  1 0/52 (0.00%)  0
Memory impairment   1/6 (16.67%)  1 1/52 (1.92%)  1
Paresthesia   0/6 (0.00%)  0 1/52 (1.92%)  1
Static cerebellar syndrom   0/6 (0.00%)  0 1/52 (1.92%)  1
Tremor   0/6 (0.00%)  0 1/52 (1.92%)  1
Vasovagal reaction   0/6 (0.00%)  0 1/52 (1.92%)  1
Psychiatric disorders     
Anxiety   1/6 (16.67%)  1 2/52 (3.85%)  2
Insomnia   2/6 (33.33%)  2 1/52 (1.92%)  1
Renal and urinary disorders     
Acute renal impairment   0/6 (0.00%)  0 1/52 (1.92%)  1
Chronic kidney disease   0/6 (0.00%)  0 1/52 (1.92%)  1
UTI   0/6 (0.00%)  0 1/52 (1.92%)  1
Reproductive system and breast disorders     
Breast pain   0/6 (0.00%)  0 2/52 (3.85%)  2
Respiratory, thoracic and mediastinal disorders     
Bronchopulmonary hemorrhage   1/6 (16.67%)  1 0/52 (0.00%)  0
Cough   1/6 (16.67%)  1 9/52 (17.31%)  12
Dyspnea   3/6 (50.00%)  4 11/52 (21.15%)  18
Epistaxis   0/6 (0.00%)  0 1/52 (1.92%)  1
Epistaxis: seasonal   0/6 (0.00%)  0 1/52 (1.92%)  1
Laryngeal inflammation   0/6 (0.00%)  0 1/52 (1.92%)  1
Nasal congestion   1/6 (16.67%)  1 0/52 (0.00%)  0
Pleural effusion   0/6 (0.00%)  0 2/52 (3.85%)  3
Pneumonia   1/6 (16.67%)  2 0/52 (0.00%)  0
Pneumonitis   0/6 (0.00%)  0 4/52 (7.69%)  4
Pneumothorax   0/6 (0.00%)  0 1/52 (1.92%)  1
Productive cough   0/6 (0.00%)  0 2/52 (3.85%)  2
Respiratory distress   0/6 (0.00%)  0 1/52 (1.92%)  1
Shortness of breath   0/6 (0.00%)  0 1/52 (1.92%)  1
Sinus disorder   0/6 (0.00%)  0 1/52 (1.92%)  1
Sore throat   0/6 (0.00%)  0 1/52 (1.92%)  1
Upper respiratory tract infection   0/6 (0.00%)  0 1/52 (1.92%)  1
Viral upper respiratory tract infection   1/6 (16.67%)  1 3/52 (5.77%)  4
Skin and subcutaneous tissue disorders     
Cutaneous rash   0/6 (0.00%)  0 1/52 (1.92%)  7
Cutaneous toxicity on legs and arms   0/6 (0.00%)  0 1/52 (1.92%)  1
Dry skin   0/6 (0.00%)  0 1/52 (1.92%)  1
Erysipelas   0/6 (0.00%)  0 1/52 (1.92%)  2
Hyperhidrosis   0/6 (0.00%)  0 1/52 (1.92%)  1
Palmar-plantar erythrodysesthesia syndrome   0/6 (0.00%)  0 1/52 (1.92%)  1
Photosensitivity   0/6 (0.00%)  0 1/52 (1.92%)  1
Pruritus   0/6 (0.00%)  0 5/52 (9.62%)  6
Rash - face   1/6 (16.67%)  1 0/52 (0.00%)  0
Rash acneiform   1/6 (16.67%)  2 2/52 (3.85%)  3
Rash maculo-papular   0/6 (0.00%)  0 3/52 (5.77%)  4
Redness ankle and feet   0/6 (0.00%)  0 1/52 (1.92%)  1
Shingles   0/6 (0.00%)  0 1/52 (1.92%)  1
Vascular disorders     
Hot flashes   0/6 (0.00%)  0 1/52 (1.92%)  1
Hypertension   0/6 (0.00%)  0 6/52 (11.54%)  12
Hypotension   0/6 (0.00%)  0 1/52 (1.92%)  1
Intracranial hypertension   0/6 (0.00%)  0 1/52 (1.92%)  1
Lymphedema   0/6 (0.00%)  0 1/52 (1.92%)  1
Lymphedema right leg   0/6 (0.00%)  0 1/52 (1.92%)  1
Thromboembolic event   0/6 (0.00%)  0 1/52 (1.92%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Heidi Roschitzki-Voser
Organization: International Breast Cancer Study Group (IBCSG)
Phone: +41 31 511 94 18
Publications:
Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT02129556     History of Changes
Other Study ID Numbers: IBCSG 45-13 / BIG 4-13
2013-004770-10 ( EudraCT Number )
First Submitted: April 24, 2014
First Posted: May 2, 2014
Results First Submitted: October 3, 2018
Results First Posted: February 15, 2019
Last Update Posted: February 15, 2019