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NCT00878709 · CITED IN SOURCE DOCUMENTS

Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2021-06-11

The purpose of this study is to investigate whether neratinib can further reduce the risk of recurrence from previously diagnosed HER-2 positive breast cancer after adjuvant treatment with trastuzumab.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2

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outcome · POSTED

Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 2

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outcome · POSTED

Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms

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outcome · POSTED

Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 2

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outcome · POSTED

Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms

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outcome · POSTED

Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 2

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outcome · POSTED

Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms

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outcome · POSTED

Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm at Year 2

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outcome · POSTED

Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 2

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outcome · POSTED

Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 5

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outcome · POSTED

Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 5 by Treatment Arms

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outcome · POSTED

Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 5

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outcome · POSTED

Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 5

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outcome · POSTED

Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 5

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outcome · POSTED

Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 5

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Stage II through IIIC HER-2/erbB-2 positive breast cancer with node positive disease. * Been treated for early breast cancer with standard of care duration of trastuzumab. * Could have been treated neoadjuvantly but have not reached pathologic complete response. Exclusion Criteria: * Positive clinical and radiologic assessments for local or regional recurrence of disease at the time of study entry. * History of heart disease. * Corrected QT (QTc) interval \>0.45 seconds * History of gastrointestinal disease with diarrhea as the major symptom.
gender Based
true
healthy Volunteers
false
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    240 mg orally daily for one year
    intervention Names
    1. Drug: neratinib
    label
    Neratinib
    type
    EXPERIMENTAL
  2. description
    orally daily for one year
    intervention Names
    1. Other: placebo
    label
    Placebo
    type
    PLACEBO_COMPARATOR
interventions
  1. arm Group Labels
    1. Neratinib
    name
    neratinib
    other Names
    1. HKI-272
    2. Nerlynx
    type
    DRUG
  2. arm Group Labels
    1. Placebo
    name
    placebo
    type
    OTHER
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
QUADRUPLE
who Masked
  1. PARTICIPANT
  2. CARE_PROVIDER
  3. INVESTIGATOR
  4. OUTCOMES_ASSESSOR
primary Purpose
TREATMENT
Enrollment
count
2840
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.
    measure
    Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 5
    time Frame
    From randomization until time of event up to 5 years
  2. measure
    Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 5 by Treatment Arms
    time Frame
    From randomization until time of event up to 5 years
  3. description
    Disease-free survival including DCIS time is defined as the time from date of randomization until the first occurrence of DCIS or an iDFS event (an iDFS event including invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, or distant recurrence and death from any.
    measure
    Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 5
    time Frame
    From randomization until time of event up to 5 years
  4. description
    Distant disease-free survival time is defined as the time from date of randomization until the first occurrence of distant recurrence or death from any cause.
    measure
    Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 5
    time Frame
    From randomization until time of event up to 5 years
  5. description
    Percentage of Participants with TTDR events is reported. TTDR is defined as the time from date of randomization until the first occurrence of distant recurrence or death from breast cancer.
    measure
    Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 5
    time Frame
    From randomization until time of event up to 5 years
  6. description
    Cumulative incidence of Central Nervous System Recurrence (CNS) is estimated by Gray's method (Gray,1988).
    measure
    Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 5
    time Frame
    From randomization until time of event up to 5 years
primary Outcomes
  1. description
    Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.
    measure
    Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2
    time Frame
    From randomization until time of event up to 2 years
  2. measure
    Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms
    time Frame
    From randomization until time of event up to 2 years
secondary Outcomes
  1. description
    OS was defined as the time from randomization to death due to any cause, censored at the last date known alive.
    measure
    Overall Survival (OS)
    time Frame
    Randomization until death due to any cause (up to 119 Months)
  2. description
    Disease-free survival including DCIS time is defined as the time from date of randomization until the first occurrence of DCIS or an iDFS event (an iDFS event including invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, or distant recurrence and death from any.
    measure
    Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 2
    time Frame
    From randomization until time of event up to 2 years
  3. measure
    Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms
    time Frame
    From randomization until time of event up to 2 years
  4. description
    Distant disease-free survival time is defined as the time from date of randomization until the first occurrence of distant recurrence or death from any cause.
    measure
    Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 2
    time Frame
    From randomization until time of event up to 2 years
  5. measure
    Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms
    time Frame
    From randomization until time of event up to 2 years
  6. description
    Percentage of Participants with TTDR events is reported. TTDR is defined as the time from date of randomization until the first occurrence of distant recurrence or death from breast cancer.
    measure
    Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 2
    time Frame
    From randomization until time of event up to 2 years
  7. measure
    Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms
    time Frame
    From randomization until time of event up to 2 years
  8. description
    CNS recurrence is defined as the time from randomization to CNS as the first distant recurrence. Competing events include distant recurrence at other sites as the first distant recurrence and death from any cause prior to distant recurrence.
    measure
    Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm at Year 2
    time Frame
    From randomization until time of event up to 2 years
  9. description
    Cumulative incidence of Central Nervous System Recurrence (CNS) is estimated by Gray's method (Gray,1988).
    measure
    Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 2
    time Frame
    From randomization until time of event up to 2 years
Full study description
brief Summary
The purpose of this study is to investigate whether neratinib can further reduce the risk of recurrence from previously diagnosed HER-2 positive breast cancer after adjuvant treatment with trastuzumab.
Source references
references
  1. citation
    Holmes FA, Moy B, Delaloge S, Chia SKL, Ejlertsen B, Mansi J, Iwata H, Gnant M, Buyse M, Barrios CH, Silovski T, Separovic R, Bashford A, Zotano AG, Denduluri N, Patt D, Gokmen E, Gore I, Smith JW 2nd, Loibl S, Masuda N, Tomasevic Z, Petrakova K, DiPrimeo D, Wong A, Martin M, Chan A; ExteNET Study Group. Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial. Eur J Cancer. 2023 May;184:48-59. doi: 10.1016/j.ejca.2023.02.002. Epub 2023 Feb 10.
    pmid
    36898233
    type
    DERIVED
  2. citation
    Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, Chiu J, Ohtani S, Takahashi M, Miyaki T, Lu YS, Xu B, Yap YS, Bustam A, Yao B, Zhang B, Bryce R, Chan A. Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer. Future Oncol. 2019 Jul;15(21):2489-2501. doi: 10.2217/fon-2019-0143. Epub 2019 May 29.
    pmid
    31140297
    type
    DERIVED
  3. citation
    Chia SKL, Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Mansi J, Barrios CH, Gnant M, Tomasevic Z, Denduluri N, Separovic R, Kim SB, Jakobsen EH, Harvey V, Robert N, Smith J 2nd, Harker G, Zhang B, Eli LD, Ye Y, Lalani AS, Buyse M, Chan A. PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial. Breast Cancer Res. 2019 Mar 11;21(1):39. doi: 10.1186/s13058-019-1115-2.
    pmid
    30867034
    type
    DERIVED
  4. citation
    Mortimer J, Di Palma J, Schmid K, Ye Y, Jahanzeb M. Patterns of occurrence and implications of neratinib-associated diarrhea in patients with HER2-positive breast cancer: analyses from the randomized phase III ExteNET trial. Breast Cancer Res. 2019 Feb 27;21(1):32. doi: 10.1186/s13058-019-1112-5.
    pmid
    30813966
    type
    DERIVED
  5. citation
    Delaloge S, Cella D, Ye Y, Buyse M, Chan A, Barrios CH, Holmes FA, Mansi J, Iwata H, Ejlertsen B, Moy B, Chia SKL, Gnant M, Smichkoska S, Ciceniene A, Martinez N, Filipovic S, Ben-Baruch NE, Joy AA, Langkjer ST, Senecal F, de Boer RH, Moran S, Yao B, Bryce R, Auerbach A, Fallowfield L, Martin M. Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial. Ann Oncol. 2019 Apr 1;30(4):567-574. doi: 10.1093/annonc/mdz016.
    pmid
    30689703
    type
    DERIVED
  6. citation
    Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomasevic Z, Denduluri N, Separovic R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. doi: 10.1016/S1470-2045(17)30717-9. Epub 2017 Nov 13.
    pmid
    29146401
    type
    DERIVED
  7. citation
    Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SKL, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-377. doi: 10.1016/S1470-2045(15)00551-3. Epub 2016 Feb 10.
    pmid
    26874901
    type
    DERIVED
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