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CompletedNCT00146172Updated Sep 17, 2018Results posted

Study Evaluating HKI-272 in Tumors

A Phase 1 interventional study of neratinib in Breast Neoplasms, sponsored by Puma Biotechnology, Inc.. Completed at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-09-17.

Sponsored by Puma Biotechnology, Inc. · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Registered 1 year 10 months after the study started (first participant enrolled Nov 2003, registered Sep 2005).
Phase
Phase 1
Study type
Interventional
Enrollment
73
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the safety and tolerability as well as find the maximum tolerated dose (MTD) for HKI-272. In addition, this study will examine the effects of the study drug on your tumor, and how your body uses and eliminates HKI-272.

02

Conditions studied

  • Breast Neoplasms

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Keywords

  • Tumors
  • Neratinib
  • HKI-272
  • Nerlynx
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 73 is close to the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Puma Biotechnology, Inc. is the lead sponsor of 38 studies on the registry; 3 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Her2/neu or Her1/EGFR positive cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

Exclusion criteria

Exclusion Criteria:

  • Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent of greater than 300 mg/m\^2
  • Patients with significant cardiac risk factors
  • Active central nervous system metastasis
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
73 participants (actual)

Study arms

  • Experimental
    Neratinib 40 mg

    Drug: neratinib

  • Experimental
    Neratinib 80 mg

    Drug: neratinib

  • Experimental
    Neratinib 120 mg

    Drug: neratinib

  • Experimental
    Neratinib 180 mg

    Drug: neratinib

  • Experimental
    Neratinib 240 mg

    Drug: neratinib

  • Experimental
    Neratinib 320 mg

    Drug: neratinib

  • Experimental
    Neratinib 400 mg

    Drug: neratinib

  • Experimental
    Neratinib 320 mg MTD

    Drug: neratinib

Interventions

  • Drugneratinib

    HKI-272

06

What researchers measure

Primary outcomes

  1. Dose Limiting Toxicity (DLT)

    DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.

    Time frame: From first dose date to day 14

  2. Maximum Tolerated Dose (MTD)

    If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.

    Time frame: From first dose date to day 14

Secondary outcomes

  1. Number of Participants With Best Overall Response

    Best Overall response by tumor type, evaluable population per Response Evaluation Criteria In Solid Tumors Criteria v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in sum of the longest diameter (LD) of target lesions in reference to baseline sum of LD of target lesions; Progressive Disease (PD), \>=20% increase in sum of LD of target lesions, taking as reference the smallest sum of recorded LD of target lesions since treatment started or appearance of 1 or more new lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD of target lesions since the treatment start. The best overall response was the best response recorded from start of treatment until PD/recurrence. In general, the subject's best response assignment depended on achievement of both measurement and confirmation criteria.

    Time frame: From first dose date to progression or last tumor assessment, up to 39 weeks.

  2. Duration of Response

    Duration of response of responders (PR+) by Kaplan-Meier estimate

    Time frame: From start date of response to first PD, up to 39 weeks.

  3. Progression Free Survival

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Time frame: From first dose date to progression or death, up to 39 weeks.

  4. Objective Response Rate

    Patients with PR or higher responses, evaluable population

    Time frame: From first dose date to progression/death or last assessment, up to 39 weeks

  5. Clinical Benefit Rate

    Patients with PR or higher responses or SD\>=24 weeks, evaluable population

    Time frame: From first dose date to progression/death or last assessment, up to 39 weeks.

07

Results

Posted Feb 13, 2018

Participant flow

Participant flow — Overall Study
MilestoneNeratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mgNeratinib MTD
Started344637640
Received drug344637639
Completed00000000
Not completed344637640
Withdrew: Adverse event001102310
Withdrew: Lost to follow-up00000001
Withdrew: Disease progression242522122
Withdrew: Death00000010
Withdrew: Physician decision00000001
Withdrew: Withdrawal by subject00000114
Withdrew: Symptomatic deterioration10101202

Outcome measures

PrimaryDose Limiting Toxicity (DLT)

DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.

Time frame:
From first dose date to day 14
Reported as:
Count of participants · Participants
Dose Limiting Toxicity (DLT)
ParticipantsNeratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mg
Dose Limiting Toxicity (DLT)0001004
SecondaryNumber of Participants With Best Overall Response

Best Overall response by tumor type, evaluable population per Response Evaluation Criteria In Solid Tumors Criteria v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in sum of the longest diameter (LD) of target lesions in reference to baseline sum of LD of target lesions; Progressive Disease (PD), \>=20% increase in sum of LD of target lesions, taking as reference the smallest sum of recorded LD of target lesions since treatment started or appearance of 1 or more new lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD of target lesions since the treatment start. The best overall response was the best response recorded from start of treatment until PD/recurrence. In general, the subject's best response assignment depended on achievement of both measurement and confirmation criteria.

Time frame:
From first dose date to progression or last tumor assessment, up to 39 weeks.
Reported as:
Count of participants · Participants
Number of Participants With Best Overall Response
ParticipantsBreast Cancer CohortLung Cancer CohortAll Subjects
Partial Response808
Stable Disease >=24 weeks167
Stable Disease >=16 weeks104
Stable Disease >=8 weeks429
Progressive Disease11632
SecondaryDuration of Response

Duration of response of responders (PR+) by Kaplan-Meier estimate

Time frame:
From start date of response to first PD, up to 39 weeks.
Reported as:
Median · months
Duration of Response
monthsBreast CancerLung CancerAll Subjects
Duration of Response4.8 (1.9 to 9.5)—4.8 (1.9 to 9.5)
SecondaryProgression Free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame:
From first dose date to progression or death, up to 39 weeks.
Reported as:
Median · months
Progression Free Survival
monthsBreast CancerLung CancerAll Subjects
Progression Free Survival3.6 (1.7 to 5.6)3.5 (1.2 to 9.0)1.9 (1.7 to 3.7)
SecondaryObjective Response Rate

Patients with PR or higher responses, evaluable population

Time frame:
From first dose date to progression/death or last assessment, up to 39 weeks
Reported as:
Number · percentage of participants
Objective Response Rate
percentage of participantsBreast CancerLung CancerAll Solid Tumors
Objective Response Rate32.0 (14.9 to 53.5)0 (NA to NA)13.3 (5.9 to 24.6)
SecondaryClinical Benefit Rate

Patients with PR or higher responses or SD\>=24 weeks, evaluable population

Time frame:
From first dose date to progression/death or last assessment, up to 39 weeks.
Reported as:
Number · percentage of participants
Clinical Benefit Rate
percentage of participantsBreast CancerLung CancerAll Solid Tumors
Clinical Benefit Rate36.0 (18.0 to 57.5)42.9 (17.7 to 71.1)25.0 (14.7 to 37.9)
PrimaryMaximum Tolerated Dose (MTD)

If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.

Time frame:
From first dose date to day 14
Reported as:
Number · mg
Maximum Tolerated Dose (MTD)
mgNeratinib 320 mg
Maximum Tolerated Dose (MTD)320

Adverse events

Collected over From first dose through 28 days after last dose, up to 39 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Neratinib 40 mg—3/3 (100%)3/3 (100%)
Neratinib 80 mg—1/4 (25%)4/4 (100%)
Neratinib 120 mg—1/4 (25%)4/4 (100%)
Neratinib 180 mg—2/6 (33.3%)6/6 (100%)
Neratinib 240 mg—0/3 (0%)3/3 (100%)
Neratinib 320 mg—4/7 (57.1%)7/7 (100%)
Neratinib 400 mg—2/6 (33.3%)6/6 (100%)
Neratinib MTD—14/39 (35.9%)39/39 (100%)
Most frequent serious events
Showing 10 of 50
Most frequent serious events
EventNeratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mgNeratinib MTD
DyspnoeaRespiratory, thoracic and mediastinal disorders2/30/40/41/60/30/70/62/39
AnaemiaBlood and lymphatic system disorders1/30/40/40/60/30/70/61/39
TachycardiaCardiac disorders1/30/40/40/60/30/70/60/39
Chest painGeneral disorders1/30/40/40/60/30/70/60/39
PneumoniaInfections and infestations1/30/40/40/60/30/70/62/39
Back painMusculoskeletal and connective tissue disorders0/30/40/42/60/30/70/60/39
Breast cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/30/40/42/60/30/70/60/39
Colon cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/30/40/40/60/30/70/60/39
Ovarian cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/30/40/40/60/30/70/60/39
PapilloedemaEye disorders0/30/41/40/60/30/70/60/39
Most frequent other events
Showing 10 of 184
Most frequent other events
EventNeratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mgNeratinib MTD
DiarrhoeaGastrointestinal disorders1/32/43/46/63/37/75/636/39
NauseaGastrointestinal disorders2/33/44/43/63/35/76/621/39
VomitingGastrointestinal disorders1/31/42/42/62/33/76/619/39
FatigueGeneral disorders3/33/43/44/62/36/75/619/39
Decreased appetiteMetabolism and nutrition disorders1/33/40/41/63/35/73/617/39
TachycardiaCardiac disorders2/31/40/40/60/30/70/61/39
Abdominal distensionGastrointestinal disorders2/30/40/40/61/30/70/63/39
Abdominal painGastrointestinal disorders2/31/40/41/60/34/71/68/39
DyspepsiaGastrointestinal disorders0/30/40/41/62/31/70/63/39
Oedema peripheralGeneral disorders2/30/40/41/60/31/70/64/39

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Neratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mgNeratinib MTDTotal
<=18 years000000000
Between 18 and 65 years34253362854
>=65 years00210401118
Age, Continuous
Age, Continuous(years)Neratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mgNeratinib MTDTotal
Mean51.33 ± 12.5054.00 ± 7.6656.25 ± 20.4360.67 ± 15.3157.00 ± 8.8963.71 ± 15.7051.33 ± 8.9158.18 ± 11.0557.68 ± 12.06
Sex: Female, Male
Sex: Female, Male(Participants)Neratinib 40 mgNeratinib 80 mgNeratinib 120 mgNeratinib 180 mgNeratinib 240 mgNeratinib 320 mgNeratinib 400 mgNeratinib MTDTotal
Female24362542652
Male10101221320
08

Study locations

5 sites
  • H. Lee Moffitt Cancer Center & Research Institute
    Tampa, Florida 33612, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • The Cleveland Clinic Foundation Taussig Cancer Center
    Cleveland, Ohio 44195, United States
  • The Sarah Cannon Cancer Center
    Nashville, Tennessee 37203, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 17, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00146172
Lead sponsor
Puma Biotechnology, Inc.
Responsible party
Sponsor
First posted
Sep 5, 2005
Start date
Nov 2003
Primary completion
Jan 2007
Completion
Jan 2007
Results posted
Feb 13, 2018
Last update
Sep 17, 2018

Study contacts

Puma
study director · Biotechnology

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2018. You cannot join it, but the record below documents what was studied.

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