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A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer

Sponsor
Puma Biotechnology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00445458
Collaborator
(none)
110
Enrollment
32
Locations
4
Arms
124.9
Actual Duration (Months)
3.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
110 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
Actual Study Start Date :
Sep 11, 2007
Actual Primary Completion Date :
May 1, 2011
Actual Study Completion Date :
Feb 7, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: HKI-272 dose level 1

Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.

Drug: HKI-272
Other Names:
  • Neratinib

    • Drug: Paclitaxel
    Experimental: HKI-272 dose level 2

    Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.

    Drug: HKI-272
    Other Names:
  • Neratinib

    • Drug: Paclitaxel
    Experimental: HKI-272 expanded MTD cohort, arm A

    Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.

    Drug: HKI-272
    Other Names:
  • Neratinib

    • Drug: Paclitaxel
    Experimental: HKI-272 expanded MTD cohort, arm B

    Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.

    Drug: HKI-272
    Other Names:
  • Neratinib

    • Drug: Paclitaxel

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel [From first dose date through day 28]

      Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.

    2. Maximum Tolerated Dose [From first dose date through day 28.]

      Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.

    3. Objective Response Rate [From first dose date to progression or last tumor assessment, up to 140 weeks]

      Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.

    Secondary Outcome Measures

    1. Maximum Plasma Concentration of Neratinib [Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.]

      Maximum plasma concentration of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.

    2. Area Under the Concentration-time Curve 0-24 [Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.]

      Area under the concentration-time curve of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Inclusion criteria for both parts of clinical trial:

    • Good performance status

    • Normal ejection fraction

    • Adequate cardiac, kidney, and liver function

    • Adequate blood counts

    • At least one measurable target lesion

    • Negative pregnancy test for female subjects

    Inclusion Criteria for Part 1 Only:
    • Pathologically confirmed solid tumor not curable with available standard therapy
    Inclusion Criteria for Part 2 Only:

    • Pathologically confirmed breast cancer

    • HER2 positive tumor

    • Prior treatment with Herceptin

    Exclusion Criteria:
    Exclusion criteria for both parts of clinical trial:

    • Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks of treatment day 1

    • Subjects with bone or skin as the only site of disease

    • Active central nervous system metastases

    • Significant cardiac disease or dysfunction

    • Significant gastrointestinal disorder

    • Inability or unwillingness to swallow HKI-272 capsules

    • Prior exposure to HKI-272 or other HER2 targeted agents, except trastuzumab (Part 2 only). Prior lapatinib is permitted in arm B of part 2.

    • Treatment with a taxane within 3 months of treatment day 1

    • Grade 2 or greater motor or sensory neuropathy

    • Pregnant or breast feeding women

    • Known hypersensitivity to paclitaxel or Cremophor EL

    • Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2

    • Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

    Exclusion Criteria for Part 2 Only:
    • More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic disease

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Scripps, Clinic General La Jolla California United States 92037
    2 Moores UC San Diego Cancer Center La Jolla California United States 92093
    3 Sharp Memorial Hospital San Diego California United States 92123
    4 Boston University Medical Center Boston Massachusetts United States 02118
    5 Mid-Michigan Physicians-HOS Division Lansing Michigan United States 48912
    6 Oncology Care Associates Saint Joseph Michigan United States 49085
    7 Columbia University Medical Center New York New York United States 10032
    8 CTRC at The University of Texas Health Science Center San Antonio Texas United States 78229
    9 Institut Jules Bordet Unite du Chimiotherapie Brussels Belgium 1000
    10 Universitair Ziekenhuis Gent Gent Belgium 9000
    11 AZ Groeninge Campus Maria's Voorzienigheid (MV) Kortrijk Belgium 8500
    12 Oncologisch Centrum GZA - Location St Augustinus Wilrijk Belgium 2610
    13 Princess Margaret Hospital University Health Network Toronto Ontario Canada M5G 2M9
    14 The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army Beijing Beijing China 100071
    15 Chinese People's Liberation Army General Hospital Beijing Beijing China 100853
    16 Tianjin Cancer Hospital TianJin Tianjin China 300060
    17 Tianjin Union Medicine Center Department of Oncology Tianjin Tianjin China 300121
    18 Cancer Hospital, Chinese Academy of Medical Sciences Beijing China 100021
    19 Peking Union Medical College Hospital of Chinese Academy of Medical Sciences Beijing China 100032
    20 UNIMED Medical Institute Hong Kong Hong Kong 0
    21 Department of Medicine, Queen Mary Hospital Hong Kong Hong Kong
    22 Department of Surgery Queen Mary Hospital Hong Kong Hong Kong
    23 Jehangir Clinical Development Centre, Jehangir Hospital Premises Pune Maharashtra India 411001
    24 M.M.F. Joshi Hospital & Ratna Memorial Hospital Pune Maharashtra India 411004
    25 Tata Memorial Hospital Mumbai Parel India 400012
    26 Birla Cancer Centre, S.M.S. Medical College & Hospital Jaipur Rajasthan India 302004
    27 Yonsei University Health System - Severance Hospital Seoul Korea, Republic of 120-752
    28 Asan Medical Center, Division of Oncology, Department of Internal Medicine Seoul Korea, Republic of 138-736
    29 Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii Krakow Poland 31-826
    30 Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej Lublin Poland 20-090
    31 City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology Dnipropetrovsk Ukraine 49102
    32 State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy Lviv Ukraine 79031

    Sponsors and Collaborators

    • Puma Biotechnology, Inc.

    Investigators

    • Study Director: Puma, Biotechnology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Puma Biotechnology, Inc.
    ClinicalTrials.gov Identifier:
    NCT00445458
    Other Study ID Numbers:
    • 3144A1-203 / B1891014
    First Posted:
    Mar 9, 2007
    Last Update Posted:
    Jul 26, 2018
    Last Verified:
    Jun 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Puma Biotechnology, Inc.
    cancer
    HKI-272
    neratinib
    paclitaxel
    Taxol
    breast cancer
    Nerlynx
    Additional relevant MeSH terms:
    Breast Neoplasms
    Paclitaxel

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Neratinib 160 mg + Paclitaxel 80 mg/m2 Neratinib 240 mg + Paclitaxel 80 mg/m2 Arm A Neratinib (MTD) + Paclitaxel 80 mg/m2 Arm B Neratinib (MTD) + Paclitaxel 80 mg/m2
    Arm/Group Description Neratinib 160 mg qd + Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Neratinib 240 mg qd + Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Neratinib (MTD) qd + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease. Neratinib (MTD) + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease.
    Period Title: Overall Study
    STARTED 3 5 71 31
    COMPLETED 0 0 3 3
    NOT COMPLETED 3 5 68 28

    Baseline Characteristics

    Arm/Group Title Neratinib 160 mg + Paclitaxel 80 mg/m2 Neratinib 240 mg + Paclitaxel 80 mg/m2 Arm A Neratinib (MTD) + Paclitaxel Arm B Neratinib (MTD) + Paclitaxel Total
    Arm/Group Description Neratinib 160 mg qd + Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Neratinib 240 mg qd + Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Neratinib (MTD) + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease Neratinib (MTD) + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease Total of all reporting groups
    Overall Participants 3 5 71 31 110
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.3
    (14.57)
    49.6
    (11.72)
    49.2
    (10.10)
    51.4
    (8.50)
    50.0
    (9.82)
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    2
    40%
    71
    100%
    31
    100%
    105
    95.5%
    Male
    2
    66.7%
    3
    60%
    0
    0%
    0
    0%
    5
    4.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    66.7%
    2
    40%
    48
    67.6%
    25
    80.6%
    77
    70%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    1
    1.4%
    0
    0%
    1
    0.9%
    White
    0
    0%
    3
    60%
    22
    31%
    5
    16.1%
    30
    27.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    33.3%
    0
    0%
    0
    0%
    1
    3.2%
    2
    1.8%

    Outcome Measures

    1. Primary Outcome
    Title Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
    Description Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
    Time Frame From first dose date through day 28

    Outcome Measure Data

    Analysis Population Description
    Safety population of Study Part 1. Treated set including patients eligible for MTD determination.
    Arm/Group Title Neratinib 160 mg + Paclitaxel 80 mg/m² Neratinib 240 mg + Paclitaxel 80 mg/m²
    Arm/Group Description Neratinib 160 mg qd + Paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle. Neratinib 240 mg qd + Paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
    Measure Participants 3 5
    Count of Participants [Participants]
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Maximum Tolerated Dose
    Description Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.
    Time Frame From first dose date through day 28.

    Outcome Measure Data

    Analysis Population Description
    Safety population of Study Part 1. Treated set including patients eligible for MTD determination.
    Arm/Group Title Part 1. Neratinib + Paclitaxel 80 mg/m²
    Arm/Group Description Daily Administration of Neratinib in combination with Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle.
    Measure Participants 8
    Number [mg]
    240
    3. Primary Outcome
    Title Objective Response Rate
    Description Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.
    Time Frame From first dose date to progression or last tumor assessment, up to 140 weeks

    Outcome Measure Data

    Analysis Population Description
    All subjects, in Study part 2 evaluable population, who met the inclusion/exclusion criteria, received at least 2 weeks of neratinib and at least 2 doses of paclitaxel, and underwent at least 1 post-Baseline tumor assessment. Subjects who died or had symptomatic deterioration before the first scheduled post-Baseline tumor assessment were included.
    Arm/Group Title Arm A Neratinib (MTD) + Paclitaxel Arm B Neratinib (MTD) + Paclitaxel
    Arm/Group Description Neratinib (MTD) + Paclitaxel 80 mg/m² on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease. Neratinib (MTD) + Paclitaxel 80 mg/m² on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 3 prior cytotoxic chemotherapy treatment regimens for metastatic disease.
    Measure Participants 68 31
    Number (95% Confidence Interval) [percentage of participants]
    70.6
    2353.3%
    77.4
    1548%
    4. Secondary Outcome
    Title Maximum Plasma Concentration of Neratinib
    Description Maximum plasma concentration of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.
    Time Frame Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Neratinib 160 mg + Paclitaxel 80 mg/m² Neratinib 240 mg + Paclitaxel 80 mg/m²
    Arm/Group Description Neratinib 160 mg, once a day, orally, in combination with paclitaxel 80 mg/m², IV, given on days 1, 8, and 15 of a 28 day cycle. Neratinib 240 mg, once a day, orally, in combination with paclitaxel 80 mg/m², IV, given on days 1, 8, and 15 of a 28 day cycle.
    Measure Participants 3 94
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    66.78
    (25)
    80.42
    (55)
    5. Secondary Outcome
    Title Area Under the Concentration-time Curve 0-24
    Description Area under the concentration-time curve of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.
    Time Frame Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Neratinib 160 mg + Paclitaxel 80 mg/m² Neratinib 240 mg + Paclitaxel 80 mg/m²
    Arm/Group Description Neratinib 160 mg, once a day, orally, in combination with paclitaxel 80 mg/m², IV, given on days 1, 8, and 15 of a 28 day cycle. Neratinib 240 mg, once a day, orally, in combination with paclitaxel 80 mg/m², IV, given on days 1, 8, and 15 of a 28 day cycle.
    Measure Participants 3 94
    Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
    684
    (92)
    1274
    (61)

    Adverse Events

    Time Frame From first dose through 28 days after last dose, up to 140 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Neratinib 160 mg + Paclitaxel 80 mg/m2 Neratinib 240 mg+ Paclitaxel 80 mg/m2 Arm A Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2 Arm B Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2
    Arm/Group Description Neratinib 160 mg qd + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Neratinib 240 mg qd + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Neratinib (MTD) qd + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease Neratinib (MTD) qd + Paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle for subjects with not more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease
    All Cause Mortality
    Neratinib 160 mg + Paclitaxel 80 mg/m2 Neratinib 240 mg+ Paclitaxel 80 mg/m2 Arm A Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2 Arm B Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Neratinib 160 mg + Paclitaxel 80 mg/m2 Neratinib 240 mg+ Paclitaxel 80 mg/m2 Arm A Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2 Arm B Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 4/5 (80%) 27/71 (38%) 4/31 (12.9%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 2/5 (40%) 0/71 (0%) 1/31 (3.2%)
    Febrile neutropenia 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Leukopenia 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Cardiac disorders
    Sinus tachycardia 1/3 (33.3%) 0/5 (0%) 0/71 (0%) 0/31 (0%)
    Eye disorders
    Cataract 0/3 (0%) 0/5 (0%) 0/71 (0%) 1/31 (3.2%)
    Gastrointestinal disorders
    Abdominal discomfort 1/3 (33.3%) 0/5 (0%) 0/71 (0%) 0/31 (0%)
    Diarrhoea 1/3 (33.3%) 1/5 (20%) 6/71 (8.5%) 0/31 (0%)
    Nausea 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Vomiting 0/3 (0%) 1/5 (20%) 2/71 (2.8%) 0/31 (0%)
    General disorders
    Fatigue 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Gait disturbance 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Oedema peripheral 0/3 (0%) 0/5 (0%) 0/71 (0%) 1/31 (3.2%)
    Pyrexia 0/3 (0%) 1/5 (20%) 1/71 (1.4%) 0/31 (0%)
    Infections and infestations
    Bacteraemia 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Cellulitis 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Cystitis 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Fungaemia 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Malaria 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Pneumonia 0/3 (0%) 0/5 (0%) 2/71 (2.8%) 0/31 (0%)
    Sepsis 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Injury, poisoning and procedural complications
    Femur fracture 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Hip fracture 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Tibia fracture 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Investigations
    Ejection fraction decreased 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Electrocardiogram T wave inversion 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/3 (0%) 0/5 (0%) 2/71 (2.8%) 0/31 (0%)
    Hypoglycaemia 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Musculoskeletal and connective tissue disorders
    Bone pain 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Pain in extremity 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer metastatic 0/3 (0%) 0/5 (0%) 4/71 (5.6%) 0/31 (0%)
    Metastases to central nervous system 0/3 (0%) 0/5 (0%) 2/71 (2.8%) 1/31 (3.2%)
    Nervous system disorders
    Brain oedema 0/3 (0%) 0/5 (0%) 0/71 (0%) 1/31 (3.2%)
    Dizziness 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Loss of consciousness 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Transient ischaemic attack 0/3 (0%) 0/5 (0%) 0/71 (0%) 1/31 (3.2%)
    Psychiatric disorders
    Anxiety 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Renal and urinary disorders
    Renal failure acute 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Dyspnoea 0/3 (0%) 1/5 (20%) 2/71 (2.8%) 0/31 (0%)
    Pneumonitis 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Pulmonary embolism 0/3 (0%) 1/5 (20%) 1/71 (1.4%) 0/31 (0%)
    Skin and subcutaneous tissue disorders
    Ingrowing nail 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Other (Not Including Serious) Adverse Events
    Neratinib 160 mg + Paclitaxel 80 mg/m2 Neratinib 240 mg+ Paclitaxel 80 mg/m2 Arm A Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2 Arm B Neratinib 240 mg (MTD) + Paclitaxel 80 mg/m2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 5/5 (100%) 70/71 (98.6%) 31/31 (100%)
    Blood and lymphatic system disorders
    Anaemia 2/3 (66.7%) 2/5 (40%) 24/71 (33.8%) 11/31 (35.5%)
    Leukopenia 0/3 (0%) 0/5 (0%) 29/71 (40.8%) 15/31 (48.4%)
    Neutropenia 0/3 (0%) 1/5 (20%) 37/71 (52.1%) 17/31 (54.8%)
    Thrombocytopenia 0/3 (0%) 0/5 (0%) 4/71 (5.6%) 1/31 (3.2%)
    Cardiac disorders
    Arrhythmia 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Palpitations 0/3 (0%) 0/5 (0%) 4/71 (5.6%) 0/31 (0%)
    Ear and labyrinth disorders
    Tinnitus 0/3 (0%) 0/5 (0%) 0/71 (0%) 2/31 (6.5%)
    Gastrointestinal disorders
    Abdominal discomfort 0/3 (0%) 0/5 (0%) 3/71 (4.2%) 3/31 (9.7%)
    Abdominal distension 1/3 (33.3%) 1/5 (20%) 5/71 (7%) 1/31 (3.2%)
    Abdominal pain 0/3 (0%) 0/5 (0%) 8/71 (11.3%) 3/31 (9.7%)
    Abdominal pain upper 0/3 (0%) 0/5 (0%) 10/71 (14.1%) 3/31 (9.7%)
    Constipation 1/3 (33.3%) 0/5 (0%) 3/71 (4.2%) 1/31 (3.2%)
    Diarrhoea 1/3 (33.3%) 5/5 (100%) 65/71 (91.5%) 29/31 (93.5%)
    Dry mouth 0/3 (0%) 1/5 (20%) 4/71 (5.6%) 1/31 (3.2%)
    Dyspepsia 0/3 (0%) 2/5 (40%) 8/71 (11.3%) 4/31 (12.9%)
    Dysphagia 0/3 (0%) 1/5 (20%) 1/71 (1.4%) 0/31 (0%)
    Gastritis 0/3 (0%) 0/5 (0%) 5/71 (7%) 3/31 (9.7%)
    Gingival ulceration 0/3 (0%) 0/5 (0%) 2/71 (2.8%) 2/31 (6.5%)
    Mouth ulceration 0/3 (0%) 0/5 (0%) 5/71 (7%) 0/31 (0%)
    Nausea 0/3 (0%) 4/5 (80%) 26/71 (36.6%) 7/31 (22.6%)
    Rectal haemorrhage 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Stomatitis 0/3 (0%) 1/5 (20%) 13/71 (18.3%) 5/31 (16.1%)
    Vomiting 0/3 (0%) 3/5 (60%) 20/71 (28.2%) 4/31 (12.9%)
    General disorders
    Asthenia 0/3 (0%) 0/5 (0%) 13/71 (18.3%) 7/31 (22.6%)
    Axillary pain 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Fatigue 1/3 (33.3%) 1/5 (20%) 16/71 (22.5%) 6/31 (19.4%)
    Generalised oedema 0/3 (0%) 0/5 (0%) 0/71 (0%) 2/31 (6.5%)
    Local swelling 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 2/31 (6.5%)
    Malaise 1/3 (33.3%) 2/5 (40%) 1/71 (1.4%) 0/31 (0%)
    Mucosal inflammation 0/3 (0%) 0/5 (0%) 6/71 (8.5%) 2/31 (6.5%)
    Oedema peripheral 0/3 (0%) 2/5 (40%) 13/71 (18.3%) 5/31 (16.1%)
    Pain 1/3 (33.3%) 0/5 (0%) 2/71 (2.8%) 1/31 (3.2%)
    Pyrexia 0/3 (0%) 0/5 (0%) 18/71 (25.4%) 4/31 (12.9%)
    Immune system disorders
    Drug hypersensitivity 1/3 (33.3%) 2/5 (40%) 1/71 (1.4%) 0/31 (0%)
    Infections and infestations
    Catheter site infection 0/3 (0%) 0/5 (0%) 0/71 (0%) 2/31 (6.5%)
    Gastroenteritis 1/3 (33.3%) 0/5 (0%) 0/71 (0%) 0/31 (0%)
    Gingivitis 0/3 (0%) 0/5 (0%) 4/71 (5.6%) 1/31 (3.2%)
    Influenza 0/3 (0%) 1/5 (20%) 6/71 (8.5%) 1/31 (3.2%)
    Nasopharyngitis 0/3 (0%) 1/5 (20%) 7/71 (9.9%) 2/31 (6.5%)
    Oral herpes 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Paronychia 0/3 (0%) 0/5 (0%) 3/71 (4.2%) 2/31 (6.5%)
    Upper respiratory tract infection 0/3 (0%) 0/5 (0%) 9/71 (12.7%) 2/31 (6.5%)
    Urinary tract infection 0/3 (0%) 1/5 (20%) 10/71 (14.1%) 5/31 (16.1%)
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0/5 (0%) 10/71 (14.1%) 6/31 (19.4%)
    Aspartate aminotransferase increased 0/3 (0%) 0/5 (0%) 9/71 (12.7%) 4/31 (12.9%)
    Blood alkaline phosphatase increased 1/3 (33.3%) 0/5 (0%) 0/71 (0%) 0/31 (0%)
    Blood urine present 1/3 (33.3%) 0/5 (0%) 0/71 (0%) 0/31 (0%)
    Weight decreased 0/3 (0%) 2/5 (40%) 10/71 (14.1%) 2/31 (6.5%)
    Metabolism and nutrition disorders
    Decreased appetite 1/3 (33.3%) 3/5 (60%) 16/71 (22.5%) 8/31 (25.8%)
    Hypocalcaemia 0/3 (0%) 0/5 (0%) 6/71 (8.5%) 3/31 (9.7%)
    Hypokalaemia 0/3 (0%) 1/5 (20%) 7/71 (9.9%) 3/31 (9.7%)
    Hypomagnesaemia 0/3 (0%) 1/5 (20%) 1/71 (1.4%) 0/31 (0%)
    Hypophagia 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Hypoproteinaemia 0/3 (0%) 0/5 (0%) 0/71 (0%) 2/31 (6.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0/5 (0%) 6/71 (8.5%) 0/31 (0%)
    Back pain 1/3 (33.3%) 0/5 (0%) 3/71 (4.2%) 5/31 (16.1%)
    Bone pain 0/3 (0%) 0/5 (0%) 5/71 (7%) 1/31 (3.2%)
    Muscle spasms 0/3 (0%) 0/5 (0%) 3/71 (4.2%) 2/31 (6.5%)
    Musculoskeletal chest pain 0/3 (0%) 1/5 (20%) 1/71 (1.4%) 0/31 (0%)
    Myalgia 0/3 (0%) 1/5 (20%) 3/71 (4.2%) 3/31 (9.7%)
    Pain in extremity 0/3 (0%) 0/5 (0%) 8/71 (11.3%) 3/31 (9.7%)
    Nervous system disorders
    Dizziness 0/3 (0%) 0/5 (0%) 7/71 (9.9%) 4/31 (12.9%)
    Headache 0/3 (0%) 0/5 (0%) 10/71 (14.1%) 5/31 (16.1%)
    Peripheral sensory neuropathy 2/3 (66.7%) 1/5 (20%) 36/71 (50.7%) 17/31 (54.8%)
    Psychiatric disorders
    Insomnia 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 2/31 (6.5%)
    Renal and urinary disorders
    Dysuria 1/3 (33.3%) 0/5 (0%) 3/71 (4.2%) 0/31 (0%)
    Hydronephrosis 1/3 (33.3%) 0/5 (0%) 0/71 (0%) 0/31 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/3 (33.3%) 1/5 (20%) 16/71 (22.5%) 2/31 (6.5%)
    Dyspnoea 1/3 (33.3%) 0/5 (0%) 9/71 (12.7%) 1/31 (3.2%)
    Epistaxis 1/3 (33.3%) 1/5 (20%) 5/71 (7%) 1/31 (3.2%)
    Nasal inflammation 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 2/31 (6.5%)
    Oropharyngeal pain 0/3 (0%) 0/5 (0%) 4/71 (5.6%) 0/31 (0%)
    Rhinorrhoea 0/3 (0%) 0/5 (0%) 3/71 (4.2%) 3/31 (9.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/3 (0%) 2/5 (40%) 37/71 (52.1%) 12/31 (38.7%)
    Decubitus ulcer 0/3 (0%) 1/5 (20%) 0/71 (0%) 0/31 (0%)
    Dermatitis acneiform 0/3 (0%) 0/5 (0%) 1/71 (1.4%) 2/31 (6.5%)
    Dry skin 1/3 (33.3%) 0/5 (0%) 1/71 (1.4%) 0/31 (0%)
    Nail disorder 0/3 (0%) 0/5 (0%) 2/71 (2.8%) 2/31 (6.5%)
    Palmar-plantar erythrodysaesthesia syndrome 0/3 (0%) 0/5 (0%) 2/71 (2.8%) 3/31 (9.7%)
    Pigmentation disorder 0/3 (0%) 0/5 (0%) 0/71 (0%) 2/31 (6.5%)
    Pruritus 0/3 (0%) 0/5 (0%) 7/71 (9.9%) 3/31 (9.7%)
    Rash 1/3 (33.3%) 2/5 (40%) 21/71 (29.6%) 8/31 (25.8%)
    Vascular disorders
    Hot flush 0/3 (0%) 1/5 (20%) 1/71 (1.4%) 1/31 (3.2%)
    Hypertension 0/3 (0%) 0/5 (0%) 5/71 (7%) 2/31 (6.5%)

    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 Senior Director, Clinical Operations
    Organization Puma Biotechnology, Inc.
    Phone +1 (424) 248-6500
    Email clinicaltrials@pumabiotechnology.com
    Responsible Party:
    Puma Biotechnology, Inc.
    ClinicalTrials.gov Identifier:
    NCT00445458
    Other Study ID Numbers:
    • 3144A1-203 / B1891014
    First Posted:
    Mar 9, 2007
    Last Update Posted:
    Jul 26, 2018
    Last Verified:
    Jun 1, 2018