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A Trial of Preoperative MM-121 With Paclitaxel in HER2-negative Breast Cancer

Sponsor
Merrimack Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01421472
Collaborator
Sanofi (Industry)
196
Enrollment
38
Locations
2
Arms
34
Duration (Months)
5.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To demonstrate whether addition of MM-121 to paclitaxel is more effective than treatment with paclitaxel alone, when administered as part of the neoadjuvant treatment in Her2 negative locally advanced operable breast cancer patients.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a multicenter, open-label, randomized, Phase II study of preoperative MM-121 with paclitaxel in HER2-negative breast cancer. Patients will be randomized to receive paclitaxel with or without MM-121 for 12 weeks followed by 4 cycles of doxorubicin plus cyclophosphamide and subsequent surgery.

Study Design

Study Type:
Interventional
Actual Enrollment :
196 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Phase 2 Trial of Preoperative MM-121 With Paclitaxel in HER2-negative Breast Cancer
Study Start Date :
Aug 1, 2011
Actual Primary Completion Date :
Dec 1, 2013
Actual Study Completion Date :
Jun 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: MM-121 (SAR256212) + paclitaxel

2 week run-in of MM-121 followed by MM-121 + dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

Drug: MM-121
MM-121 IV at 40 mg/mg loading dose on Cycle 1, Week 1 followed by 20 mg/mg weekly for all subsequent doses
Other Names:
  • SAR256212

    • Drug: Paclitaxel
    Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.
    Active Comparator: Paclitaxel only

    Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

    Drug: Paclitaxel
    Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) [At time of surgery, an expected average of 24-26 weeks]

      Pathologic Complete Response was defined as the absence of invasive cancer in the breast and lymph nodes following completion of neoadjuvant systemic therapy and reported according to the current AJCC staging system for neoadjuvant clinical studies. The endpoint was to determine the pathologic Complete Response (pCR) rates associated with weekly treatment of MM-121 plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide compared with weekly paclitaxel alone followed by the combination treatment of doxorubicin plus cyclophosphamide in patients with human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histological confirmation of ER positive, HER2 negative invasive breast cancer (Group
    1. or invasive triple-negative breast cancer (Group 2)

    • Free of metastatic disease

    • ≥ 18 years old

    • Female

    • Had no prior treatment for any cancer

    • Eligible for treatment with paclitaxel, doxorubicin and cyclophosphamide

    Exclusion Criteria:

    • Have a history of severe allergic reactions to paclitaxel or other drugs formulated in Cremaphor® EL

    • Are pregnant or breastfeeding

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Universito of Birmingham atAlabama Birmingham Alabama United States 35294
    2 Arizona Oncology Associates Tucson Arizona United States 85704
    3 Arizona Oncology Associates Tuscon Arizona United States 85715
    4 Marin Cancer Center Greenbrae California United States 94904
    5 PMK Medical Group Oxnard California United States 93030
    6 Wilshire Oncology Medical Group Rancho Cucamonga California United States 91730
    7 Florida Cancer Research Institute Plantation Florida United States 33324
    8 Piedmont Healthcare Altanta Georgia United States 30214
    9 Piedmont Fayette Hospital Fayetteville Georgia United States 30214
    10 Georgia Cancer Specialists Marietta Georgia United States 30341
    11 University Of Chicago Chicago Illinois United States 60637
    12 Illinois Cancer Specialists Niles Illinois United States 60714
    13 Dana-Farber Cancer Institute Boston Massachusetts United States 02114
    14 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    15 Beaumont Health Systems Royal Oak Michigan United States 48073
    16 Comprehensive Cancer Centers of Nevada Henderson Nevada United States 89074
    17 Cooper Cancer Institute Voorhees New Jersey United States 08043
    18 University of New Mexico Cancer Center Albuquerque New Mexico United States 87106
    19 Memorial Medical Center Las Cruces New Mexico United States 88011
    20 Northwest Cancer Specialists Portland Oregon United States 97225
    21 Cancer Center of the Carolinas Greenville South Carolina United States 29605
    22 Texas Oncology - Amarillo Amarillo Texas United States 79106
    23 Texas Oncology-Austin Central Austin Texas United States 78731
    24 Texas Oncology - Bedford Bedford Texas United States 76022
    25 Texas Oncology - Medical City Dallas Texas United States 75230
    26 Texas Oncology - Dallas Dallas Texas United States 75231
    27 Texas Oncology - Baylor Charles A Sammons Cancer Center Dallas Texas United States 75246
    28 Texas Oncology -El Paso El Paso Texas United States 79902
    29 Texas Oncology - Garland Garland Texas United States 75042
    30 Texas Oncology - Memorial City Houston Texas United States 77024
    31 Texas Oncology - Lewisville Lewisville Texas United States 75067
    32 Texas Oncology - McAllen McAllen Texas United States 78503
    33 Texas Oncology Plano East Plano Texas United States 75075-7787
    34 Cancer Care Centers of South Texas San Antonio Texas United States 78217
    35 Texas Oncology - Tyler Tyler Texas United States 75702
    36 Virginia Oncology Associates Norfolk Virginia United States 23502
    37 Puget Sound Cancer Center Seattle Washington United States 98133
    38 Yakima Valley Memorial Hospital Yakima Washington United States 98902

    Sponsors and Collaborators

    • Merrimack Pharmaceuticals
    • Sanofi

    Investigators

    • Study Director: Victor Moyo, MD, Merrimack Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merrimack Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01421472
    Other Study ID Numbers:
    • MM-121-02-02-07 (ARD11918)
    First Posted:
    Aug 22, 2011
    Last Update Posted:
    May 3, 2016
    Last Verified:
    Mar 1, 2016
    Keywords provided by Merrimack Pharmaceuticals
    Breast Cancer
    Neoadjuvant
    Her2 negative
    Her2 non-overexpressing
    Estrogen Receptor Positive
    Triple Negative
    MM-121
    Paclitaxel
    Additional relevant MeSH terms:
    Breast Neoplasms
    Triple Negative Breast Neoplasms
    Paclitaxel

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel
    Arm/Group Description Hormone-receptor positive (HR+) sub-group randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Hormone-receptor positive (HR+) sub-group randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. Triple Negative (TN) patients randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Triple negative (TN) patients randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.
    Period Title: Overall Study
    STARTED 67 33 64 32
    COMPLETED 67 33 64 32
    NOT COMPLETED 0 0 0 0

    Baseline Characteristics

    Arm/Group Title HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel Total
    Arm/Group Description Hormone-receptor positive (HR+) sub-group randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Hormone-receptor positive (HR+) sub-group randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. Triple Negative (TN) patients randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Triple negative (TN) patients randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. Total of all reporting groups
    Overall Participants 67 33 64 32 196
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    50.7
    (10.35)
    48.9
    (10.53)
    49.3
    (10.89)
    52.5
    (13.45)
    50.25
    (11.12)
    Sex: Female, Male (Count of Participants)
    Female
    67
    100%
    33
    100%
    64
    100%
    32
    100%
    196
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    10
    14.9%
    10
    30.3%
    13
    20.3%
    3
    9.4%
    36
    18.4%
    Not Hispanic or Latino
    57
    85.1%
    22
    66.7%
    51
    79.7%
    29
    90.6%
    159
    81.1%
    Unknown or Not Reported
    0
    0%
    1
    3%
    0
    0%
    0
    0%
    1
    0.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    1.5%
    0
    0%
    0
    0%
    0
    0%
    1
    0.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    3%
    0
    0%
    0
    0%
    1
    0.5%
    Black or African American
    7
    10.4%
    4
    12.1%
    11
    17.2%
    5
    15.6%
    27
    13.8%
    White
    57
    85.1%
    26
    78.8%
    48
    75%
    26
    81.3%
    157
    80.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    2
    3%
    2
    6.1%
    5
    7.8%
    1
    3.1%
    10
    5.1%
    Region of Enrollment (participants) [Number]
    United States
    67
    100%
    33
    100%
    64
    100%
    32
    100%
    196
    100%
    Subject of Child-Bearing Potential (Y/N) (participants) [Number]
    Yes
    32
    47.8%
    19
    57.6%
    27
    42.2%
    12
    37.5%
    90
    45.9%
    No
    35
    52.2%
    14
    42.4%
    37
    57.8%
    20
    62.5%
    106
    54.1%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR)
    Description Pathologic Complete Response was defined as the absence of invasive cancer in the breast and lymph nodes following completion of neoadjuvant systemic therapy and reported according to the current AJCC staging system for neoadjuvant clinical studies. The endpoint was to determine the pathologic Complete Response (pCR) rates associated with weekly treatment of MM-121 plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide compared with weekly paclitaxel alone followed by the combination treatment of doxorubicin plus cyclophosphamide in patients with human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer.
    Time Frame At time of surgery, an expected average of 24-26 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects with evaluable resection.
    Arm/Group Title HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel
    Arm/Group Description Hormone-receptor positive (HR+) sub-group randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Hormone-receptor positive (HR+) sub-group randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. Triple Negative (TN) patients randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Triple negative (TN) patients randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.
    Measure Participants 66 30 56 29
    Subjects with no pCR
    59
    88.1%
    29
    87.9%
    32
    50%
    14
    43.8%
    Subjects with pCR
    7
    10.4%
    1
    3%
    24
    37.5%
    15
    46.9%

    Adverse Events

    Time Frame Adverse events were collected from a patient's first dose until 30 days after treatment termination. Serious adverse events were collected from time of informed consent until 30 days after treatment termination, or any time when assumed to be related
    Adverse Event Reporting Description All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for ~1 year after termination.
    Arm/Group Title HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel
    Arm/Group Description Hormone-receptor positive (HR+) sub-group randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Hormone-receptor positive (HR+) sub-group randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. Triple Negative (TN) patients randomized to receive: 2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) Triple negative (TN) patients randomized to receive: Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.
    All Cause Mortality
    HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/67 (20.9%) 5/33 (15.2%) 18/64 (28.1%) 5/32 (15.6%)
    Blood and lymphatic system disorders
    Febrile Neutropenia 5/67 (7.5%) 0/33 (0%) 6/64 (9.4%) 2/32 (6.3%)
    Anemia 3/67 (4.5%) 0/33 (0%) 4/64 (6.3%) 0/32 (0%)
    Neutropenia 0/67 (0%) 0/33 (0%) 3/64 (4.7%) 0/32 (0%)
    Leukopenia 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Cardiac disorders
    Sinus Tachycardia 0/67 (0%) 0/33 (0%) 0/64 (0%) 1/32 (3.1%)
    Gastrointestinal disorders
    Diarrhea 2/67 (3%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Nausea 1/67 (1.5%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Vomiting 1/67 (1.5%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Pancreatitis 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    General disorders
    Pyrexia 1/67 (1.5%) 1/33 (3%) 1/64 (1.6%) 0/32 (0%)
    Infections and infestations
    Bacteremia 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Breast Cellulutis 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Cellulitis 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Clostridial Infection 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Gastroenteritis 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Infected Cyst 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Infective Thrombosis 0/67 (0%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Influenza 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Lung Infection 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Pneumonia 0/67 (0%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Sepsis 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Staphylococcal Infection 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Urinary Tract Infection 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Injury, poisoning and procedural complications
    Infusion Related Reaction 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Seroma 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Investigations
    Electrocardiogram QT Prolonged 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Metabolism and nutrition disorders
    Dehydration 2/67 (3%) 0/33 (0%) 1/64 (1.6%) 1/32 (3.1%)
    Hyperkalemia 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Hypovolemia 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Musculoskeletal and connective tissue disorders
    Muscular Weakness 0/67 (0%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Nervous system disorders
    Presyncope 0/67 (0%) 0/33 (0%) 0/64 (0%) 1/32 (3.1%)
    Syncope 0/67 (0%) 0/33 (0%) 0/64 (0%) 1/32 (3.1%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism 1/67 (1.5%) 0/33 (0%) 3/64 (4.7%) 0/32 (0%)
    Dyspnea 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 1/32 (3.1%)
    Hypoxia 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Pneumonitis 0/67 (0%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Vascular disorders
    Hypertension 0/67 (0%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Hypotension 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Jugular Vein Thrombosis 0/67 (0%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Thrombophlebitis 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 0/32 (0%)
    Other (Not Including Serious) Adverse Events
    HR+: MM-121+ Paclitaxel HR+: Paclitaxel Only TN: MM-121 + Paclitaxel TN: Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 67/67 (100%) 33/33 (100%) 64/64 (100%) 32/32 (100%)
    Blood and lymphatic system disorders
    Anemia 32/67 (47.8%) 13/33 (39.4%) 24/64 (37.5%) 12/32 (37.5%)
    Neutropenia 21/67 (31.3%) 9/33 (27.3%) 18/64 (28.1%) 7/32 (21.9%)
    Leukopenia 8/67 (11.9%) 2/33 (6.1%) 7/64 (10.9%) 3/32 (9.4%)
    Febrile Neutropenia 7/67 (10.4%) 1/33 (3%) 8/64 (12.5%) 3/32 (9.4%)
    Leukocytosis 5/67 (7.5%) 1/33 (3%) 0/64 (0%) 0/32 (0%)
    Cardiac disorders
    Tachycardia 4/67 (6%) 1/33 (3%) 6/64 (9.4%) 0/32 (0%)
    Palpitations 4/67 (6%) 1/33 (3%) 3/64 (4.7%) 0/32 (0%)
    Ear and labyrinth disorders
    Ear Pain 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 2/32 (6.3%)
    Eye disorders
    Vision Blurred 8/67 (11.9%) 4/33 (12.1%) 8/64 (12.5%) 4/32 (12.5%)
    Dry Eye 4/67 (6%) 2/33 (6.1%) 0/64 (0%) 3/32 (9.4%)
    Lacrimatino Increased 3/67 (4.5%) 2/33 (6.1%) 3/64 (4.7%) 1/32 (3.1%)
    Conjunctivitis 3/67 (4.5%) 2/33 (6.1%) 1/64 (1.6%) 0/32 (0%)
    Gastrointestinal disorders
    Nausea 52/67 (77.6%) 24/33 (72.7%) 48/64 (75%) 24/32 (75%)
    Diarrhea 55/67 (82.1%) 12/33 (36.4%) 56/64 (87.5%) 15/32 (46.9%)
    Constipation 12/67 (17.9%) 13/33 (39.4%) 27/64 (42.2%) 15/32 (46.9%)
    Vomiting 16/67 (23.9%) 10/33 (30.3%) 17/64 (26.6%) 7/32 (21.9%)
    Dyspepsia 13/67 (19.4%) 8/33 (24.2%) 18/64 (28.1%) 8/32 (25%)
    Stomatitis 16/67 (23.9%) 2/33 (6.1%) 20/64 (31.3%) 7/32 (21.9%)
    Gastroesophageal Reflux Disease 13/67 (19.4%) 4/33 (12.1%) 11/64 (17.2%) 3/32 (9.4%)
    Abdominal Pain 7/67 (10.4%) 4/33 (12.1%) 10/64 (15.6%) 2/32 (6.3%)
    Oral Pain 10/67 (14.9%) 2/33 (6.1%) 8/64 (12.5%) 2/32 (6.3%)
    Hemorrhoids 6/67 (9%) 0/33 (0%) 9/64 (14.1%) 2/32 (6.3%)
    Dry Mouth 5/67 (7.5%) 3/33 (9.1%) 2/64 (3.1%) 2/32 (6.3%)
    Proctalgia 5/67 (7.5%) 1/33 (3%) 2/64 (3.1%) 0/32 (0%)
    Toothache 0/67 (0%) 0/33 (0%) 5/64 (7.8%) 0/32 (0%)
    Dysphagia 2/67 (3%) 2/33 (6.1%) 2/64 (3.1%) 2/32 (6.3%)
    Abdominal Distension 3/67 (4.5%) 1/33 (3%) 2/64 (3.1%) 2/32 (6.3%)
    Abdominal Pain Upper 2/67 (3%) 2/33 (6.1%) 2/64 (3.1%) 0/32 (0%)
    Mouth Ulceration 2/67 (3%) 0/33 (0%) 2/64 (3.1%) 2/32 (6.3%)
    General disorders
    Fatigue 54/67 (80.6%) 21/33 (63.6%) 50/64 (78.1%) 28/32 (87.5%)
    Mucosal Inflammation 17/67 (25.4%) 5/33 (15.2%) 11/64 (17.2%) 8/32 (25%)
    Pyrexia 17/67 (25.4%) 8/33 (24.2%) 8/64 (12.5%) 6/32 (18.8%)
    Peripheral edema 10/67 (14.9%) 9/33 (27.3%) 11/64 (17.2%) 6/32 (18.8%)
    Pain 2/67 (3%) 3/33 (9.1%) 8/64 (12.5%) 3/32 (9.4%)
    Asthenia 3/67 (4.5%) 2/33 (6.1%) 4/64 (6.3%) 2/32 (6.3%)
    Chills 1/67 (1.5%) 1/33 (3%) 5/64 (7.8%) 3/32 (9.4%)
    Chest Pain 4/67 (6%) 0/33 (0%) 4/64 (6.3%) 1/32 (3.1%)
    Catheter Site Pain 0/67 (0%) 2/33 (6.1%) 3/64 (4.7%) 1/32 (3.1%)
    Chest Discomfort 2/67 (3%) 2/33 (6.1%) 1/64 (1.6%) 1/32 (3.1%)
    Non-cardiac Chest Pain 1/67 (1.5%) 0/33 (0%) 0/64 (0%) 2/32 (6.3%)
    Immune system disorders
    Hypersensitivity 0/67 (0%) 0/33 (0%) 2/64 (3.1%) 2/32 (6.3%)
    Infections and infestations
    Upper Respiratory Tract Infection 12/67 (17.9%) 4/33 (12.1%) 11/64 (17.2%) 4/32 (12.5%)
    Urinary Tract Infection 11/67 (16.4%) 2/33 (6.1%) 11/64 (17.2%) 3/32 (9.4%)
    Sinusitis 5/67 (7.5%) 0/33 (0%) 6/64 (9.4%) 2/32 (6.3%)
    Folliculitis 3/67 (4.5%) 3/33 (9.1%) 4/64 (6.3%) 1/32 (3.1%)
    Oral Herpes 3/67 (4.5%) 0/33 (0%) 5/64 (7.8%) 1/32 (3.1%)
    Oral Candidiasis 0/67 (0%) 3/33 (9.1%) 4/64 (6.3%) 0/32 (0%)
    Fungal Infection 1/67 (1.5%) 1/33 (3%) 4/64 (6.3%) 0/32 (0%)
    Vulvovaginal Mycotic Infection 1/67 (1.5%) 0/33 (0%) 4/64 (6.3%) 0/32 (0%)
    Nasopharyngitis 3/67 (4.5%) 4/33 (12.1%) 2/64 (3.1%) 2/32 (6.3%)
    Nail Infection 3/67 (4.5%) 0/33 (0%) 1/64 (1.6%) 3/32 (9.4%)
    Pharyngitis 1/67 (1.5%) 2/33 (6.1%) 2/64 (3.1%) 1/32 (3.1%)
    Candidiasis 2/67 (3%) 0/33 (0%) 1/64 (1.6%) 2/32 (6.3%)
    Injury, poisoning and procedural complications
    Infusion Related Reaction 3/67 (4.5%) 3/33 (9.1%) 6/64 (9.4%) 2/32 (6.3%)
    Procedural Pain 3/67 (4.5%) 2/33 (6.1%) 3/64 (4.7%) 0/32 (0%)
    Investigations
    Weight Decreased 19/67 (28.4%) 5/33 (15.2%) 17/64 (26.6%) 8/32 (25%)
    Alanine Aminotransferase Increased 5/67 (7.5%) 2/33 (6.1%) 4/64 (6.3%) 0/32 (0%)
    Aspartate Aminotransferase Increased 5/67 (7.5%) 2/33 (6.1%) 4/64 (6.3%) 0/32 (0%)
    Metabolism and nutrition disorders
    Decreased Appetite 18/67 (26.9%) 7/33 (21.2%) 17/64 (26.6%) 11/32 (34.4%)
    Hypokalemia 21/67 (31.3%) 3/33 (9.1%) 9/64 (14.1%) 2/32 (6.3%)
    Dehydration 10/67 (14.9%) 4/33 (12.1%) 11/64 (17.2%) 3/32 (9.4%)
    Hypomagnesemia 11/67 (16.4%) 3/33 (9.1%) 7/64 (10.9%) 3/32 (9.4%)
    Hyperglycemia 5/67 (7.5%) 1/33 (3%) 7/64 (10.9%) 1/32 (3.1%)
    Hypophosphatemia 5/67 (7.5%) 1/33 (3%) 4/64 (6.3%) 0/32 (0%)
    Hypocalcemia 5/67 (7.5%) 0/33 (0%) 2/64 (3.1%) 0/32 (0%)
    Musculoskeletal and connective tissue disorders
    Myalgia 11/67 (16.4%) 8/33 (24.2%) 14/64 (21.9%) 9/32 (28.1%)
    Arthralgia 14/67 (20.9%) 8/33 (24.2%) 11/64 (17.2%) 7/32 (21.9%)
    Bone Pain 11/67 (16.4%) 2/33 (6.1%) 11/64 (17.2%) 4/32 (12.5%)
    Back Pain 10/67 (14.9%) 2/33 (6.1%) 7/64 (10.9%) 6/32 (18.8%)
    Pain in Extremity 6/67 (9%) 5/33 (15.2%) 7/64 (10.9%) 5/32 (15.6%)
    Muscle Spasm 7/67 (10.4%) 1/33 (3%) 6/64 (9.4%) 4/32 (12.5%)
    Muscular Weakness 2/67 (3%) 2/33 (6.1%) 5/64 (7.8%) 6/32 (18.8%)
    Musculoskeletal pain 4/67 (6%) 3/33 (9.1%) 1/64 (1.6%) 3/32 (9.4%)
    Nervous system disorders
    Peripheral neuropathy 32/67 (47.8%) 17/33 (51.5%) 37/64 (57.8%) 18/32 (56.3%)
    Headache 19/67 (28.4%) 13/33 (39.4%) 10/64 (15.6%) 9/32 (28.1%)
    Dysgeusia 14/67 (20.9%) 8/33 (24.2%) 20/64 (31.3%) 5/32 (15.6%)
    Dizziness 11/67 (16.4%) 6/33 (18.2%) 10/64 (15.6%) 3/32 (9.4%)
    Peripheral sensory neuropathy9 8/67 (11.9%) 5/33 (15.2%) 9/64 (14.1%) 2/32 (6.3%)
    Parasthesia 7/67 (10.4%) 4/33 (12.1%) 6/64 (9.4%) 4/32 (12.5%)
    Hypoasthesia 2/67 (3%) 2/33 (6.1%) 5/64 (7.8%) 3/32 (9.4%)
    Syncope 4/67 (6%) 1/33 (3%) 2/64 (3.1%) 1/32 (3.1%)
    Restless leg syndrome 4/67 (6%) 1/33 (3%) 1/64 (1.6%) 0/32 (0%)
    Hyperasthesia 1/67 (1.5%) 2/33 (6.1%) 1/64 (1.6%) 1/32 (3.1%)
    Sinus Headache 0/67 (0%) 0/33 (0%) 2/64 (3.1%) 3/32 (9.4%)
    Disturbance in Attention 0/67 (0%) 0/33 (0%) 1/64 (1.6%) 2/32 (6.3%)
    Psychiatric disorders
    Insomnia 21/67 (31.3%) 10/33 (30.3%) 20/64 (31.3%) 10/32 (31.3%)
    Anxiety 10/67 (14.9%) 3/33 (9.1%) 6/64 (9.4%) 6/32 (18.8%)
    Depression 8/67 (11.9%) 4/33 (12.1%) 4/64 (6.3%) 2/32 (6.3%)
    Agitation 0/67 (0%) 2/33 (6.1%) 0/64 (0%) 1/32 (3.1%)
    Renal and urinary disorders
    Dysuria 7/67 (10.4%) 2/33 (6.1%) 8/64 (12.5%) 2/32 (6.3%)
    Pollakuria 0/67 (0%) 1/33 (3%) 2/64 (3.1%) 2/32 (6.3%)
    Urinary Incontinence 2/67 (3%) 1/33 (3%) 0/64 (0%) 2/32 (6.3%)
    Nocturia 0/67 (0%) 0/33 (0%) 0/64 (0%) 2/32 (6.3%)
    Reproductive system and breast disorders
    Breast Pain 6/67 (9%) 0/33 (0%) 5/64 (7.8%) 0/32 (0%)
    Vaginal Hemorrhage 1/67 (1.5%) 1/33 (3%) 4/64 (6.3%) 2/32 (6.3%)
    Vulvovaginal Dryness 1/67 (1.5%) 0/33 (0%) 2/64 (3.1%) 2/32 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 18/67 (26.9%) 5/33 (15.2%) 19/64 (29.7%) 6/32 (18.8%)
    Epistaxis 18/67 (26.9%) 4/33 (12.1%) 20/64 (31.3%) 3/32 (9.4%)
    Oropharyngeal Pain 7/67 (10.4%) 9/33 (27.3%) 5/64 (7.8%) 8/32 (25%)
    Dyspnea 7/67 (10.4%) 4/33 (12.1%) 8/64 (12.5%) 5/32 (15.6%)
    Rhinorrhea 4/67 (6%) 5/33 (15.2%) 3/64 (4.7%) 2/32 (6.3%)
    Nasal Congestion 5/67 (7.5%) 0/33 (0%) 4/64 (6.3%) 2/32 (6.3%)
    Dyspnea Exertional 3/67 (4.5%) 1/33 (3%) 4/64 (6.3%) 1/32 (3.1%)
    Rhinitis Allergic 6/67 (9%) 1/33 (3%) 0/64 (0%) 2/32 (6.3%)
    Nasal Dryness 1/67 (1.5%) 0/33 (0%) 4/64 (6.3%) 1/32 (3.1%)
    Productive Cough 4/67 (6%) 0/33 (0%) 1/64 (1.6%) 0/32 (0%)
    Sinus Congestion 3/67 (4.5%) 3/33 (9.1%) 0/64 (0%) 1/32 (3.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 42/67 (62.7%) 22/33 (66.7%) 42/64 (65.6%) 21/32 (65.6%)
    Rash 28/67 (41.8%) 5/33 (15.2%) 27/64 (42.2%) 8/32 (25%)
    Nail Disorder 9/67 (13.4%) 3/33 (9.1%) 16/64 (25%) 3/32 (9.4%)
    Pruritis 7/67 (10.4%) 5/33 (15.2%) 9/64 (14.1%) 4/32 (12.5%)
    Dry Skin 9/67 (13.4%) 1/33 (3%) 10/64 (15.6%) 3/32 (9.4%)
    Nail Discoloration 11/67 (16.4%) 2/33 (6.1%) 6/64 (9.4%) 4/32 (12.5%)
    Skin Hyperpigmentation 6/67 (9%) 2/33 (6.1%) 6/64 (9.4%) 2/32 (6.3%)
    Rash Maculo-papular 6/67 (9%) 1/33 (3%) 4/64 (6.3%) 1/32 (3.1%)
    Erythema 5/67 (7.5%) 1/33 (3%) 3/64 (4.7%) 1/32 (3.1%)
    Skin Discoloration 4/67 (6%) 2/33 (6.1%) 2/64 (3.1%) 2/32 (6.3%)
    Palmar-Plantar Erythrodysasthesia Syndrome 3/67 (4.5%) 0/33 (0%) 4/64 (6.3%) 1/32 (3.1%)
    Rash Pruritic 5/67 (7.5%) 0/33 (0%) 3/64 (4.7%) 0/32 (0%)
    Onycholysis 4/67 (6%) 1/33 (3%) 2/64 (3.1%) 0/32 (0%)
    Pain of Skin 5/67 (7.5%) 0/33 (0%) 2/64 (3.1%) 0/32 (0%)
    Nail Bed Tenderness 4/67 (6%) 0/33 (0%) 0/64 (0%) 1/32 (3.1%)
    Night Sweats 1/67 (1.5%) 2/33 (6.1%) 1/64 (1.6%) 2/32 (6.3%)
    Rash Macular 1/67 (1.5%) 0/33 (0%) 3/64 (4.7%) 2/32 (6.3%)
    Dermatitis Acneform 2/67 (3%) 1/33 (3%) 0/64 (0%) 2/32 (6.3%)
    Vascular disorders
    Hot Flush 10/67 (14.9%) 6/33 (18.2%) 8/64 (12.5%) 8/32 (25%)
    Hypotension 6/67 (9%) 2/33 (6.1%) 5/64 (7.8%) 2/32 (6.3%)
    Hypertension 2/67 (3%) 3/33 (9.1%) 3/64 (4.7%) 0/32 (0%)
    Flushing 4/67 (6%) 0/33 (0%) 3/64 (4.7%) 1/32 (3.1%)
    Lymphoedema 1/67 (1.5%) 0/33 (0%) 4/64 (6.3%) 1/32 (3.1%)
    Deep Vein Thrombosis 0/67 (0%) 2/33 (6.1%) 0/64 (0%) 0/32 (0%)
    Jugular Vein Thrombosis 0/67 (0%) 2/33 (6.1%) 0/64 (0%) 0/32 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title Clinical Trial Manager
    Organization Merrimack Pharmaceuticals
    Phone 617-441-1000
    Email smathews@merrimack.com
    Responsible Party:
    Merrimack Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01421472
    Other Study ID Numbers:
    • MM-121-02-02-07 (ARD11918)
    First Posted:
    Aug 22, 2011
    Last Update Posted:
    May 3, 2016
    Last Verified:
    Mar 1, 2016