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A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)

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ClinicalTrials.gov Identifier: NCT01120184
Recruitment Status : Completed
First Posted : May 10, 2010
Results First Posted : February 23, 2017
Last Update Posted : November 7, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: docetaxel
Drug: paclitaxel
Drug: pertuzumab
Drug: pertuzumab-placebo
Drug: trastuzumab [Herceptin]
Drug: trastuzumab emtansine

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Trastuzumab + Taxane Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

Participant Flow:   Overall Study
    Trastuzumab + Taxane   Trastuzumab Emtansine + Placebo   Trastuzumab Emtansine + Pertuzumab
STARTED   365   367   363 
Treated   355   365   360 
COMPLETED   0   0   0 
NOT COMPLETED   365   367   363 
Adverse Event                0                1                0 
Lost to Follow-up                13                13                11 
Physician Decision                9                1                3 
Reason not Specified                8                3                12 
Sponsor Decision to Terminate Study                133                144                143 
Subject/ Guardian Decision to Withdraw                32                29                25 
Death                170                176                169 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: All participants randomized in the study.

Reporting Groups
  Description
Trastuzumab + Taxane Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Total Total of all reporting groups

Baseline Measures
   Trastuzumab + Taxane   Trastuzumab Emtansine + Placebo   Trastuzumab Emtansine + Pertuzumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 365   367   363   1095 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.2  (11.3)   52.6  (11.4)   52.2  (12.0)   53.0  (11.6) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      362  99.2%      365  99.5%      361  99.4%      1088  99.4% 
Male      3   0.8%      2   0.5%      2   0.6%      7   0.6% 


  Outcome Measures

1.  Primary:   Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

2.  Primary:   Progression-Free Survival (PFS) According to IRF Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

3.  Secondary:   Percentage of Participants Who Died Prior to Clinical Cutoff   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

4.  Secondary:   Overall Survival (OS) at Clinical Cutoff   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

5.  Secondary:   Percentage of Participants With Death or Disease Progression According to Investigator Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

6.  Secondary:   PFS According to Investigator Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

7.  Secondary:   Percentage of Participants Experiencing Treatment Failure   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

8.  Secondary:   Time to Treatment Failure (TTF)   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

9.  Secondary:   One-Year Survival Rate   [ Time Frame: From randomization until 1 year ]

10.  Secondary:   Percentage of Participants With Grade ≥3 Adverse Events   [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose ]

11.  Secondary:   Percentage of Participants Who Died at 2 Years   [ Time Frame: From randomization until 2 years ]

12.  Secondary:   Overall Survival Truncated at 2 Years   [ Time Frame: From randomization until 2 years ]

13.  Secondary:   Percentage of Participants With Grade 5 Adverse Events   [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose) ]

14.  Secondary:   Percentage of Participants With Grade 3-4 Laboratory Parameters   [ Time Frame: Day 1, 8, and 15 of Cycle 1–3 and on Day 1 of each subsequent cycle up to 50 months from randomization until clinical cutoff of 16-Sept-2014 ]

15.  Secondary:   Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status   [ Time Frame: Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months) ]

16.  Secondary:   Hospitalization Days   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

17.  Secondary:   Percentage of Participants With Hospitalization   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

18.  Secondary:   Percentage of Participants With Objective Response According to IRF Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

19.  Secondary:   Percentage of Participants With Objective Response According to Investigator Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

20.  Secondary:   Duration of Response According to IRF Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

21.  Secondary:   Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

22.  Secondary:   Percentage of Participants Experiencing a Clinically Significant Increase in Taxane-Related Treatment Symptoms as Measured by Taxane Subscale of the Functional Assessment of Cancer Therapy (FACT) Taxane (FACT-TaxS) Score   [ Time Frame: Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose) ]

23.  Secondary:   Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module   [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]

24.  Secondary:   Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module   [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]

25.  Secondary:   Percentage of Participants With a Clinically Significant Deterioration in Health Related Quality of Life (HRQoL) as Measured by FACT Breast (FACT-B) Trial Outcome Index-Physical Function Breast (TOI-PFB) Score   [ Time Frame: Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose) ]

26.  Secondary:   Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score   [ Time Frame: Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014 ]

27.  Secondary:   Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score   [ Time Frame: Baseline, Cycle 7 (Week 18) ]

28.  Secondary:   Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score   [ Time Frame: Baseline, Cycle 7 (Week 18) ]

29.  Secondary:   Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score   [ Time Frame: Baseline, Cycle 7 (Week 18) ]

30.  Secondary:   Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

31.  Secondary:   Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

32.  Secondary:   Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

33.  Secondary:   PFS According to IRF Assessment Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

34.  Secondary:   Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

35.  Secondary:   PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

36.  Secondary:   Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

37.  Secondary:   OS at Clinical Cutoff Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

38.  Secondary:   Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

39.  Secondary:   OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]


  Serious Adverse Events


  Other Adverse Events

Time Frame Up to 70 months from randomization until clinical cutoff of 16 September 2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination).
Additional Description Safety Population: All randomized participants who received at least one dose of study treatment and the participants were analyzed based on the treatment they actually received (N=353 in Trastuzumab + Taxane arm, N=361 in Trastuzumab Emtansine, Pertuzumab-placebo arm, N=366 in Trastuzumab emtansine + pertuzumab arm).

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Trastuzumab + Taxane Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

Other Adverse Events
    Trastuzumab + Taxane   Trastuzumab Emtansine + Placebo   Trastuzumab Emtansine + Pertuzumab
Total, Other (not including serious) Adverse Events       
# participants affected / at risk   342/353 (96.88%)   352/361 (97.51%)   352/366 (96.17%) 
Blood and lymphatic system disorders       
Neutropenia * 1       
# participants affected / at risk   74/353 (20.96%)   44/361 (12.19%)   37/366 (10.11%) 
Anaemia * 1       
# participants affected / at risk   39/353 (11.05%)   48/361 (13.30%)   59/366 (16.12%) 
Thrombocytopenia * 1       
# participants affected / at risk   0/353 (0.00%)   52/361 (14.40%)   61/366 (16.67%) 
Ear and labyrinth disorders       
Vertigo * 2       
# participants affected / at risk   11/353 (3.12%)   17/361 (4.71%)   21/366 (5.74%) 
Eye disorders       
Lacrimation increased * 1       
# participants affected / at risk   48/353 (13.60%)   13/361 (3.60%)   19/366 (5.19%) 
Dry eye * 1       
# participants affected / at risk   13/353 (3.68%)   25/361 (6.93%)   24/366 (6.56%) 
Vision Blurred † 2       
# participants affected / at risk   10/353 (2.83%)   13/361 (3.60%)   19/366 (5.19%) 
Gastrointestinal disorders       
Nausea * 1       
# participants affected / at risk   131/353 (37.11%)   174/361 (48.20%)   192/366 (52.46%) 
Diarrhoea * 2       
# participants affected / at risk   173/353 (49.01%)   92/361 (25.48%)   178/366 (48.63%) 
Vomiting * 1       
# participants affected / at risk   69/353 (19.55%)   80/361 (22.16%)   111/366 (30.33%) 
Constipation * 1       
# participants affected / at risk   72/353 (20.40%)   82/361 (22.71%)   71/366 (19.40%) 
Stomatitis * 1       
# participants affected / at risk   57/353 (16.15%)   37/361 (10.25%)   42/366 (11.48%) 
Dyspepsia * 1       
# participants affected / at risk   38/353 (10.76%)   33/361 (9.14%)   48/366 (13.11%) 
Abdominal pain upper * 1       
# participants affected / at risk   31/353 (8.78%)   39/361 (10.80%)   46/366 (12.57%) 
Dry mouth * 1       
# participants affected / at risk   13/353 (3.68%)   52/361 (14.40%)   45/366 (12.30%) 
Abdominal pain * 1       
# participants affected / at risk   31/353 (8.78%)   35/361 (9.70%)   41/366 (11.20%) 
Gingival bleeding * 1       
# participants affected / at risk   4/353 (1.13%)   31/361 (8.59%)   25/366 (6.83%) 
Haemorrhoids * 1       
# participants affected / at risk   9/353 (2.55%)   12/361 (3.32%)   22/366 (6.01%) 
General disorders       
Fatigue * 2       
# participants affected / at risk   128/353 (36.26%)   120/361 (33.24%)   130/366 (35.52%) 
Pyrexia * 1       
# participants affected / at risk   59/353 (16.71%)   96/361 (26.59%)   118/366 (32.24%) 
Asthenia * 1       
# participants affected / at risk   57/353 (16.15%)   62/361 (17.17%)   63/366 (17.21%) 
Chills * 1       
# participants affected / at risk   14/353 (3.97%)   55/361 (15.24%)   97/366 (26.50%) 
Oedema peripheral * 1       
# participants affected / at risk   98/353 (27.76%)   37/361 (10.25%)   35/366 (9.56%) 
Mucosal inflammation * 1       
# participants affected / at risk   40/353 (11.33%)   29/361 (8.03%)   36/366 (9.84%) 
Influenza like illness * 1       
# participants affected / at risk   17/353 (4.82%)   31/361 (8.59%)   32/366 (8.74%) 
Non-cardiac chest pain * 1       
# participants affected / at risk   24/353 (6.80%)   25/361 (6.93%)   27/366 (7.38%) 
Pain * 1       
# participants affected / at risk   29/353 (8.22%)   26/361 (7.20%)   19/366 (5.19%) 
Oedema * 1       
# participants affected / at risk   31/353 (8.78%)   11/361 (3.05%)   3/366 (0.82%) 
Infections and infestations       
Upper respiratory tract infection * 1       
# participants affected / at risk   55/353 (15.58%)   50/361 (13.85%)   66/366 (18.03%) 
Nasopharyngitis * 1       
# participants affected / at risk   49/353 (13.88%)   52/361 (14.40%)   66/366 (18.03%) 
Urinary tract infection * 1       
# participants affected / at risk   29/353 (8.22%)   31/361 (8.59%)   41/366 (11.20%) 
Rhinitis * 1       
# participants affected / at risk   18/353 (5.10%)   25/361 (6.93%)   24/366 (6.56%) 
Influenza * 1       
# participants affected / at risk   14/353 (3.97%)   22/361 (6.09%)   25/366 (6.83%) 
Paronychia * 1       
# participants affected / at risk   22/353 (6.23%)   8/361 (2.22%)   30/366 (8.20%) 
Pharyngitis * 1       
# participants affected / at risk   14/353 (3.97%)   19/361 (5.26%)   17/366 (4.64%) 
Conjunctivitis * 1       
# participants affected / at risk   21/353 (5.95%)   14/361 (3.88%)   17/366 (4.64%) 
Bronchitis † 2       
# participants affected / at risk   14/353 (3.97%)   9/361 (2.49%)   20/366 (5.46%) 
Investigations       
Aspartate aminotransferase increased * 1       
# participants affected / at risk   9/353 (2.55%)   54/361 (14.96%)   28/366 (7.65%) 
Alanine aminotranseferase increased * 1       
# participants affected / at risk   10/353 (2.83%)   41/361 (11.36%)   35/366 (9.56%) 
Weight decreased * 1       
# participants affected / at risk   7/353 (1.98%)   24/361 (6.65%)   30/366 (8.20%) 
Ejection fraction decreased * 1       
# participants affected / at risk   31/353 (8.78%)   7/361 (1.94%)   16/366 (4.37%) 
Gamma- glutamyltranseferase increased * 1       
# participants affected / at risk   1/353 (0.28%)   30/361 (8.31%)   17/366 (4.64%) 
Metabolism and nutrition disorders       
Decreased appetite * 1       
# participants affected / at risk   76/353 (21.53%)   84/361 (23.27%)   84/366 (22.95%) 
Hypokalaemia * 1       
# participants affected / at risk   15/353 (4.25%)   19/361 (5.26%)   30/366 (8.20%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1       
# participants affected / at risk   91/353 (25.78%)   83/361 (22.99%)   71/366 (19.40%) 
Myalgia * 1       
# participants affected / at risk   82/353 (23.23%)   66/361 (18.28%)   61/366 (16.67%) 
Back pain * 1       
# participants affected / at risk   46/353 (13.03%)   60/361 (16.62%)   63/366 (17.21%) 
Pain in extremity * 1       
# participants affected / at risk   48/353 (13.60%)   53/361 (14.68%)   54/366 (14.75%) 
Muscle spasms * 1       
# participants affected / at risk   15/353 (4.25%)   32/361 (8.86%)   62/366 (16.94%) 
Musculoskeletal pain * 1       
# participants affected / at risk   23/353 (6.52%)   30/361 (8.31%)   37/366 (10.11%) 
Bone pain * 1       
# participants affected / at risk   33/353 (9.35%)   17/361 (4.71%)   29/366 (7.92%) 
Musculoskeletal chest pain * 1       
# participants affected / at risk   17/353 (4.82%)   13/361 (3.60%)   20/366 (5.46%) 
Neck Pain * 1       
# participants affected / at risk   12/353 (3.40%)   12/361 (3.32%)   24/366 (6.56%) 
Nervous system disorders       
Headache * 1       
# participants affected / at risk   80/353 (22.66%)   116/361 (32.13%)   120/366 (32.79%) 
Neuropathy peripheral * 1       
# participants affected / at risk   99/353 (28.05%)   52/361 (14.40%)   69/366 (18.85%) 
Peripheral sensory neuropathy * 1       
# participants affected / at risk   70/353 (19.83%)   47/361 (13.02%)   46/366 (12.57%) 
Dysgeusia * 1       
# participants affected / at risk   54/353 (15.30%)   30/361 (8.31%)   50/366 (13.66%) 
Paraesthesia * 1       
# participants affected / at risk   41/353 (11.61%)   31/361 (8.59%)   43/366 (11.75%) 
Dizziness * 1       
# participants affected / at risk   35/353 (9.92%)   38/361 (10.53%)   38/366 (10.38%) 
Psychiatric disorders       
Insomnia * 1       
# participants affected / at risk   51/353 (14.45%)   51/361 (14.13%)   52/366 (14.21%) 
Anxiety * 1       
# participants affected / at risk   22/353 (6.23%)   26/361 (7.20%)   33/366 (9.02%) 
Depression * 1       
# participants affected / at risk   17/353 (4.82%)   34/361 (9.42%)   20/366 (5.46%) 
Reproductive system and breast disorders       
Breast pain * 1       
# participants affected / at risk   18/353 (5.10%)   13/361 (3.60%)   16/366 (4.37%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis * 1       
# participants affected / at risk   53/353 (15.01%)   113/361 (31.30%)   127/366 (34.70%) 
Cough * 1       
# participants affected / at risk   74/353 (20.96%)   72/361 (19.94%)   79/366 (21.58%) 
Dyspnoea * 1       
# participants affected / at risk   56/353 (15.86%)   42/361 (11.63%)   53/366 (14.48%) 
Oropharyngeal pain * 1       
# participants affected / at risk   29/353 (8.22%)   31/361 (8.59%)   30/366 (8.20%) 
Rhinorrhoea * 1       
# participants affected / at risk   26/353 (7.37%)   21/361 (5.82%)   32/366 (8.74%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1       
# participants affected / at risk   212/353 (60.06%)   26/361 (7.20%)   33/366 (9.02%) 
Rash * 1       
# participants affected / at risk   86/353 (24.36%)   62/361 (17.17%)   89/366 (24.32%) 
Pruritus * 1       
# participants affected / at risk   32/353 (9.07%)   28/361 (7.76%)   51/366 (13.93%) 
Nail disorder * 1       
# participants affected / at risk   39/353 (11.05%)   11/361 (3.05%)   19/366 (5.19%) 
Dry skin * 1       
# participants affected / at risk   24/353 (6.80%)   24/361 (6.65%)   29/366 (7.92%) 
Erythema * 1       
# participants affected / at risk   24/353 (6.80%)   13/361 (3.60%)   20/366 (5.46%) 
Dermatitis acneiform * 1       
# participants affected / at risk   6/353 (1.70%)   16/361 (4.43%)   27/366 (7.38%) 
Palmar-plantar erythrodysaesthesia syndrome * 1       
# participants affected / at risk   26/353 (7.37%)   6/361 (1.66%)   11/366 (3.01%) 
Nail discolouration * 1       
# participants affected / at risk   25/353 (7.08%)   5/361 (1.39%)   1/366 (0.27%) 
Onychoclasis * 2       
# participants affected / at risk   13/353 (3.68%)   19/361 (5.26%)   17/366 (4.64%) 
Vascular disorders       
Hypertension * 1       
# participants affected / at risk   19/353 (5.38%)   37/361 (10.25%)   43/366 (11.75%) 
Hot flush * 1       
# participants affected / at risk   27/353 (7.65%)   16/361 (4.43%)   12/366 (3.28%) 
Lymphoedema * 1       
# participants affected / at risk   27/353 (7.65%)   7/361 (1.94%)   8/366 (2.19%) 
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (17.1)
2 Term from vocabulary, MedDRA (19.0)



  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01120184     History of Changes
Other Study ID Numbers: BO22589
2009-017905-13 ( EudraCT Number )
First Submitted: April 28, 2010
First Posted: May 10, 2010
Results First Submitted: May 2, 2016
Results First Posted: February 23, 2017
Last Update Posted: November 7, 2017