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Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca. (HERiTAge)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02472964
Recruitment Status : Completed
First Posted : June 16, 2015
Results First Posted : October 30, 2018
Last Update Posted : February 14, 2022
Sponsor:
Collaborator:
Mylan GmbH
Information provided by (Responsible Party):
Viatris Inc. ( Mylan Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Biological: Trastuzumab
Biological: MYL- 1401O
Drug: Paclitaxel
Drug: Docetaxel
Enrollment 500
Recruitment Details 500 subjects enrolled at 95 sites across Eastern Europe, Russia, Asia Pacific, Africa and South America. The intent to treat1(ITT1) population of 458 was used to determine Primary Outcome of Overall Response Rate.
Pre-assignment Details The primary efficacy analysis was derived fromITT1 population 230 (MYL-1401O) + 228 (Herceptin)= 458. Safety analysis was derived from the Safety Population 247(MYL-1401O)+246(Herceptin)= 493. Total Randomized population 249(MYL-1401O) +251(Herceptin)= 500.
Arm/Group Title Herceptin© + Taxane HerMyl 1401O Trastuzumab + Taxane
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Part 1: Herceptin© (trastuzumab) intravenously+ paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Herceptin© (trastuzumab) alone once every 3 weeks until DP or subject withdrawal .

Part 1:Myl 1401OTrastuzumab Intravenously + paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Myl 1401O( Mylan Trastuzumab) alone once every 3 weeks until DP or subject withdrawal.

Period Title: Part 1 (up to Week 24)
Started [1] 246 247
Completed 171 185
Not Completed 75 62
Reason Not Completed
Adverse Event             2             4
disease progression             58             47
Death             3             6
Physician Decision             3             1
Lost to Follow-up             0             1
Withdrawal by Subject             7             2
Other             2             1
[1]
The disposition of the patients has been provided for the safety sample population.
Period Title: Part 2 (Week 24-week 48)
Started [1] 163 179
Completed 98 116
Not Completed 65 63
Reason Not Completed
Adverse Event             4             2
Disease Progression             52             56
Death             0             1
Physician Decision             1             1
Lost to Follow-up             2             1
Withdrawal by Subject             3             1
Protocol Violation             3             1
[1]
The disposition of the patients has been provided for the safety sample.
Arm/Group Title Herceptin© + Taxane MYL-1401O + Taxane Total
Hide Arm/Group Description

Part 1: Herceptin© (trastuzumab) intravenously+ paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Herceptin© (trastuzumab) alone once every 3 weeks until DP or subject withdrawal .

Herceptin© 8mg/kg Iv over 90 minutes x 1 then Herceptin© 6 mg/kg IV over 30 minutes every 3 weeks

Paclitaxel 80mg/m2 IV over 60 minutes weekly.

Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle

Part 1:MYL-1401O intravenously + paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Myl 1401O alone once every 3 weeks until DP or subject withdrawal.

MYL-1401O 8mg/kg Iv over 90 minutes x 1 then MYL-1401O 6 mg/kg IV over 30 minutes every 3 weeks

Paclitaxel 80mg/m2 IV over 60 minutes weekly.

Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle

Total of all reporting groups
Overall Number of Baseline Participants 228 230 458
Hide Baseline Analysis Population Description
Bseline Analysis Population Description: The primary efficacy endpoint analysis was conducted in the intention to treat (IIT)population ( only those patients randomized after the second amendment of the protocol)
Age, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 228 participants 230 participants 458 participants
< 50years of age
86
  37.7%
74
  32.2%
160
  34.9%
>/= 50years of age
142
  62.3%
156
  67.8%
298
  65.1%
[1]
Measure Analysis Population Description: The primary efficacy endpoint analysis was conducted in the intention to treat (IIT1)population ( only those patients randomized after the second amendment of the protocol)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 228 participants 230 participants 458 participants
Female
228
 100.0%
230
 100.0%
458
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 228 participants 230 participants 458 participants
American Indian or Alaska Native 0 0 0
Asian 72 70 142
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 2 1 3
White 154 159 313
More than one race 0 0 0
Unknown or Not Reported 0 0 0
[1]
Measure Analysis Population Description: The primary efficacy endpoint analysis was conducted in the intention to treat (IIT1)population ( only those patients randomized after the second amendment of the protocol)
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 228 participants 230 participants 458 participants
Chile 4 1 5
Czechia 1 0 1
Georgia 23 26 49
Hungary 8 5 13
India 31 24 55
Latvia 2 4 6
Philippines 18 30 48
Poland 6 13 19
Romania 5 3 8
Russia 73 71 144
Serbia 2 3 5
Slovakia 1 2 3
South Africa 3 8 11
Thailand 23 16 39
Ukraine 28 24 52
1.Primary Outcome
Title Primary Endpoint : Compare Best Overall Response Rate (ORR) (According to Response Evaluation Criteria in Solid Tumor [RECIST] 1.1 Criteria) at Week 24 of MYL-1401O Plus Taxane Versus Herceptin® Plus Taxane in the ITT1 Population
Hide Description

Tumor measurements were perform by centralized blinded reviewers using RECIST 1.1 criteria. Per RECIST 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to <10 mm.Partial Response (PR): >/= 30% decrease sum of the diameters of target lesions from baseline sum diameters.

Progressive Disease (PD): </= 20% increase in the sum of the diameters of target lesions, from the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions* denotes disease progression.

Stable Disease (SD): Neither sufficient decrease or increase. Evaluation of Non-Target Lesions Complete Response (CR): Disappearance of all non-target lesions. Non-complete Response/Non-Progressive Disease: Persistence of one or more non-target lesions. Progressive Disease (PD): Substantial, unequivocal progression of existing non-target lesions.

Time Frame from time of First treatment to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis was conducted in the Intent To Treat population 1 (ITT1) ( all patients randomized after Amendment 2 of the protocol)
Arm/Group Title Herceptin© + Taxane MYL-1401O Trastuzumab + Taxane
Hide Arm/Group Description:

Part 1: Herceptin© (trastuzumab) intravenously+ paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Herceptin© (trastuzumab) alone once every 3 weeks until DP or subject withdrawal .

Part 1:Myl 1401OTrastuzumab Intravenously + paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Myl 1401O( Mylan Trastuzumab) alone once every 3 weeks until DP or subject withdrawal.

Overall Number of Participants Analyzed 228 230
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
3
   1.3%
Partial Response
146
  64.0%
157
  68.3%
Stable Disease
49
  21.5%
48
  20.9%
Progressive Disease
20
   8.8%
9
   3.9%
Not Evaluable
13
   5.7%
13
   5.7%
Time Frame ICF until 28 days( +/- 7 days) after last dose of IMP per patient. The active reporting period for AEs is from the time the patient receives the first dose until 28 days( +/- 7 days) after last administered dose of IMP per patient. However, SAEs should be reported any time after the active reporting period, when the Investigator becomes aware and the SAE is considered to be reasonably related to the study drug.
Adverse Event Reporting Description

The Investigator is responsible for the detection and documentation of events meeting the criteria and definition of an AE or SAE, as described previously. At each visit, the patient will be allowed time to spontaneously report any issues since the last visit or evaluation.

The Investigator will then monitor and/or ask about or evaluate AEs using non-leading questions. Any clinically relevant observations made during the visit are also to be considered AEs.

 
Arm/Group Title Herceptin© + Taxane Myl 1401O Trastuzumab + Taxane
Hide Arm/Group Description

Part 1: Herceptin© (trastuzumab) intravenously+ paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Herceptin© (trastuzumab) alone once every 3 weeks until DP or subject withdrawal .

Part 1:Myl 1401OTrastuzumab Intravenously + paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Myl 1401O( Mylan Trastuzumab) alone once every 3 weeks until DP or subject withdrawal.

All-Cause Mortality
Herceptin© + Taxane Myl 1401O Trastuzumab + Taxane
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Herceptin© + Taxane Myl 1401O Trastuzumab + Taxane
Affected / at Risk (%) Affected / at Risk (%)
Total   91/246 (36.99%)   97/247 (39.27%) 
Blood and lymphatic system disorders     
Febrile Neutropenia  1  10/246 (4.07%)  11/247 (4.45%) 
Leukopenia  1  12/246 (4.88%)  5/247 (2.02%) 
Neutropenia  1  62/246 (25.20%)  68/247 (27.53%) 
Pancytopenia  1  0/246 (0.00%)  1/247 (0.40%) 
Thrombocytopenia  1  1/246 (0.41%)  0/247 (0.00%) 
Cardiac disorders     
Acute Myocardial Infarction  1  0/246 (0.00%)  1/247 (0.40%) 
Cardiac Failure  1  0/246 (0.00%)  2/247 (0.81%) 
Carditis  1  0/246 (0.00%)  1/247 (0.40%) 
Gastrointestinal disorders     
Abdominal Pain  1  0/246 (0.00%)  1/247 (0.40%) 
Anal Fissure  1  0/246 (0.00%)  1/247 (0.40%) 
Diarrhoea  1  4/246 (1.63%)  3/247 (1.21%) 
Duodenal Ulcer Perforation  1  1/246 (0.41%)  0/247 (0.00%) 
Gastritis  1  1/246 (0.41%)  0/247 (0.00%) 
Gastrointestinal Toxicity  1  1/246 (0.41%)  0/247 (0.00%) 
Nausea  1  1/246 (0.41%)  2/247 (0.81%) 
Rectal Perforation  1  1/246 (0.41%)  0/247 (0.00%) 
Vomiting  1  3/246 (1.22%)  1/247 (0.40%) 
General disorders     
Death  1  1/246 (0.41%)  0/247 (0.00%) 
Fatigue  1  1/246 (0.41%)  0/247 (0.00%) 
Hyperthermia  1  1/246 (0.41%)  0/247 (0.00%) 
Malaise  1  0/246 (0.00%)  1/247 (0.40%) 
Multi-Organ Failure  1  0/246 (0.00%)  1/247 (0.40%) 
Pyrexia  1  2/246 (0.81%)  0/247 (0.00%) 
Hepatobiliary disorders     
Cholecystitis Chronic  1  0/246 (0.00%)  1/247 (0.40%) 
Cholelithiasis  1  1/246 (0.41%)  0/247 (0.00%) 
Hepatic Failure  1  1/246 (0.41%)  1/247 (0.40%) 
Immune system disorders     
Anaphylactic Reaction  1  0/246 (0.00%)  2/247 (0.81%) 
Drug Hypersensitivity  1  0/246 (0.00%)  1/247 (0.40%) 
Hypersensitivity  1  2/246 (0.81%)  0/247 (0.00%) 
Infections and infestations     
Bronchitis  1  2/246 (0.81%)  0/247 (0.00%) 
Gastroenteritis  1  1/246 (0.41%)  3/247 (1.21%) 
Influenza  1  1/246 (0.41%)  0/247 (0.00%) 
Mastitis  1  1/246 (0.41%)  0/247 (0.00%) 
Paronychia  1  0/246 (0.00%)  1/247 (0.40%) 
Pneumonia  1  5/246 (2.03%)  6/247 (2.43%) 
Rectal Abscess  1  1/246 (0.41%)  0/247 (0.00%) 
Renal Abscess  1  0/246 (0.00%)  1/247 (0.40%) 
Sepsis  1  3/246 (1.22%)  0/247 (0.00%) 
Septic Shock  1  0/246 (0.00%)  1/247 (0.40%) 
Tubo-Ovarian Abscess  1  1/246 (0.41%)  0/247 (0.00%) 
Upper Respiratory Tract Infection  1  0/246 (0.00%)  1/247 (0.40%) 
Urosepsis  1  0/246 (0.00%)  1/247 (0.40%) 
Urinary Tract Infection  1  1/246 (0.41%)  2/247 (0.81%) 
Wound Infection  1  1/246 (0.41%)  0/247 (0.00%) 
Injury, poisoning and procedural complications     
Femur Fracture  1  1/246 (0.41%)  0/247 (0.00%) 
Infusion Related Reaction  1  1/246 (0.41%)  0/247 (0.00%) 
Investigations     
Blood Uric Acid Increased  1  1/246 (0.41%)  1/247 (0.40%) 
Ejection Fraction Decreased  1  0/246 (0.00%)  1/247 (0.40%) 
White Blood Cell Count Decreased  1  0/246 (0.00%)  1/247 (0.40%) 
Metabolism and nutrition disorders     
Hypernatraemia  1  2/246 (0.81%)  0/247 (0.00%) 
Hyperuricaemia  1  2/246 (0.81%)  2/247 (0.81%) 
Hypokalemia  1  1/246 (0.41%)  1/247 (0.40%) 
Tumour Lysis Syndrome  1  1/246 (0.41%)  0/247 (0.00%) 
Hyponatraemia  1  2/246 (0.81%)  0/247 (0.00%) 
Musculoskeletal and connective tissue disorders     
Pathological Fracture  1  1/246 (0.41%)  0/247 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lymphanangiosis Carcinomatosa  1  1/246 (0.41%)  0/247 (0.00%) 
Nervous system disorders     
Cerebral Infarction  1  1/246 (0.41%)  0/247 (0.00%) 
Headache  1  1/246 (0.41%)  0/247 (0.00%) 
Transient Ischaemic Attack  1  0/246 (0.00%)  1/247 (0.40%) 
Renal and urinary disorders     
Acute Kidney Injury  1  1/246 (0.41%)  1/247 (0.40%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/246 (0.00%)  2/247 (0.81%) 
Pleural Effusion  1  1/246 (0.41%)  1/247 (0.40%) 
Pneumonitis  1  2/246 (0.81%)  1/247 (0.40%) 
Pneumothorax Spontaneous  1  0/246 (0.00%)  1/247 (0.40%) 
Pulmonary Embolism  1  1/246 (0.41%)  0/247 (0.00%) 
Pulmonary Haemorrhage  1  1/246 (0.41%)  0/247 (0.00%) 
Respiratory Failure  1  1/246 (0.41%)  2/247 (0.81%) 
Vascular disorders     
Accelerated Hypertension  1  0/246 (0.00%)  1/247 (0.40%) 
Deep Vein Thrombosis  1  0/246 (0.00%)  1/247 (0.40%) 
Peripheral Ischaemia  1  0/246 (0.00%)  1/247 (0.40%) 
Thrombophlebitis Superficial  1  0/246 (0.00%)  1/247 (0.40%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Herceptin© + Taxane Myl 1401O Trastuzumab + Taxane
Affected / at Risk (%) Affected / at Risk (%)
Total   232/246 (94.31%)   229/247 (92.71%) 
Blood and lymphatic system disorders     
Neutropenia  1  83/246 (33.74%)  91/247 (36.84%) 
Leukopenia  1  42/246 (17.07%)  40/247 (16.19%) 
Anemia  1  44/246 (17.89%)  41/247 (16.60%) 
Gastrointestinal disorders     
Diarrhea  1  49/246 (19.92%)  50/247 (20.24%) 
Nausea  1  37/246 (15.04%)  51/247 (20.65%) 
Vomiting  1  21/246 (8.54%)  26/247 (10.53%) 
Decreased Appetite  1  25/246 (10.16%)  23/247 (9.31%) 
General disorders     
Oedema Peripheral  1  31/246 (12.60%)  38/247 (15.38%) 
Fatigue  1  36/246 (14.63%)  30/247 (12.15%) 
Pyrexia  1  31/246 (12.60%)  24/247 (9.72%) 
Peripheral Swelling  1  13/246 (5.28%)  11/247 (4.45%) 
Infections and infestations     
Urninary Tract Infection  1  18/246 (7.32%)  23/247 (9.31%) 
Upper Respiratory Infection  1  5/246 (2.03%)  18/247 (7.29%) 
Injury, poisoning and procedural complications     
Infusion Related Reaction  1  11/246 (4.47%)  17/247 (6.88%) 
Investigations     
Alanine Aminotransferase Increased  1  22/246 (8.94%)  22/247 (8.91%) 
Aspartate Amniotransferase Increased  1  24/246 (9.76%)  16/247 (6.48%) 
Metabolism and nutrition disorders     
Hyperglycemia  1  19/246 (7.72%)  15/247 (6.07%) 
Musculoskeletal and connective tissue disorders     
Asthenia  1  41/246 (16.67%)  57/247 (23.08%) 
Myalgia  1  23/246 (9.35%)  25/247 (10.12%) 
Arthralgia  1  14/246 (5.69%)  33/247 (13.36%) 
Bone Pain  1  14/246 (5.69%)  21/247 (8.50%) 
Nervous system disorders     
Neuropathy Peripheral  1  30/246 (12.20%)  31/247 (12.55%) 
Headache  1  28/246 (11.38%)  24/247 (9.72%) 
Peripheral Sensory Neuropathy  1  36/246 (14.63%)  32/247 (12.96%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  18/246 (7.32%)  19/247 (7.69%) 
Dyspnea  1  18/246 (7.32%)  15/247 (6.07%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  135/246 (54.88%)  143/247 (57.89%) 
Rash  1  25/246 (10.16%)  22/247 (8.91%) 
Nail Disorder  1  22/246 (8.94%)  17/247 (6.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Program Manager
Organization: Mylan Inc
Phone: 412-651-9530
EMail: gail.tribble@mylan.com
Layout table for additonal information
Responsible Party: Viatris Inc. ( Mylan Inc. )
ClinicalTrials.gov Identifier: NCT02472964    
Other Study ID Numbers: MYL-Her 3001
2011-001965-42 ( EudraCT Number )
First Submitted: June 3, 2015
First Posted: June 16, 2015
Results First Submitted: October 12, 2017
Results First Posted: October 30, 2018
Last Update Posted: February 14, 2022