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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01953926




Registration number
NCT01953926
Ethics application status
Date submitted
26/09/2013
Date registered
1/10/2013
Date last updated
22/07/2021

Titles & IDs
Public title
Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Scientific title
An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
Secondary ID [1] 0 0
2013-002872-42
Secondary ID [2] 0 0
PUMA-NER-5201
Universal Trial Number (UTN)
Trial acronym
SUMMIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Neratinib
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Trastuzumab

Experimental: Neratinib monotherapy - Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, and lung cancers containing EGFR exon 18 mutations.

Experimental: Neratinib and Trastuzumab - Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers.

Experimental: Neratinib, Fulvestrant and Trastuzumab (Randomized) - Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.

Experimental: Neratinib, Fulvestrant and Trastuzumab (Non-Randomized) - Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers.


Treatment: Drugs: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles

Treatment: Drugs: Fulvestrant
500 mg administered as two 5 mL injections on Days 1, 15, and 29; then once every 4 weeks thereafter month, then Day 1 of every 4 week cycle

Treatment: Drugs: Trastuzumab
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Confirmed Objective Response Rate (Breast, Cervical Cohorts) - Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer, and metastatic cervical cancer cohorts)
Timepoint [1] 0 0
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months
Primary outcome [2] 0 0
Objective Response Rate - First Tumor Assessment (Other Cohorts) - Percentage of participants who achieve CR or PR per RECIST v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts)
Timepoint [2] 0 0
From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy
Timepoint [1] 0 0
From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 18 months
Secondary outcome [2] 0 0
Confirmed Objective Response Rate (Other Cohorts) - Percentage of participants who are confirmed by independent central review to have achieved CR or PR according to RECIST v1.1 (all other cohorts)
Timepoint [2] 0 0
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months
Secondary outcome [3] 0 0
Objective Response Rate - First Tumor Assessment (Breast, Cervical Cohorts) - Percentage of participants who achieve CR or PR according to RECIST v1.1, or other defined response criteria, at the first scheduled tumor assessment (HR+, HER2 negative metastatic breast cancer, and metastatic cervical cancer cohorts)
Timepoint [3] 0 0
From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR) - Percentage of participants with CR + PR + stable disease =16, or =24 weeks for breast cancer, from the date of enrollment
Timepoint [4] 0 0
From enrollment date to first documented response or stable disease =16, or =24 weeks for breast cancer, assessed up to 18 months
Secondary outcome [5] 0 0
Duration of Response (DOR) - Time from which measurement criteria are met for confirmed overall response of CR or PR (whichever status is recorded first) until the first date of documented disease progression
Timepoint [5] 0 0
From first response to first disease progression or death, assessed up to 18 months
Secondary outcome [6] 0 0
Overall Survival (OS) - Time from Cycle 1 Day 1 to death due to any cause
Timepoint [6] 0 0
From enrollment date to death, assessed up to two years
Secondary outcome [7] 0 0
Incidence of Treatment-Emergent Adverse Events - Treatment-emergent and serious adverse events that occurred on or after first dose of investigational product and up to 28 days after the last dose
Timepoint [7] 0 0
From first dose through 28 days after the last dose, assessed up to 18 months

Eligibility
Key inclusion criteria
- Provide written informed consent

- Histologically confirmed cancers for which no curative therapy exists

- Documented HER2 or EGFR exon 18 mutation

- Participants must agree and commit to use appropriate methods of contraception as
outlined in the protocol

- At least one measurable lesion, defined by RECIST v1.1
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants harboring ineligible somatic HER2 mutations

- Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib,
afatinib, dacomitinib, neratinib) is excluded with the following exception: patients
with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other
pan HER or EGFR TKIs remain eligible

- Participants who are receiving any other anticancer agents

- Symptomatic or unstable brain metastases

- Women who are pregnant or breast-feeding

There are additional inclusion and exclusion criteria. The study center will determine if
criteria for participation are met.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
8006 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
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United States of America
State/province [3] 0 0
California
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United States of America
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Delaware
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United States of America
State/province [5] 0 0
Florida
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United States of America
State/province [6] 0 0
Georgia
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United States of America
State/province [7] 0 0
Illinois
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United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
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United States of America
State/province [17] 0 0
South Carolina
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United States of America
State/province [18] 0 0
Tennessee
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United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Canada
State/province [23] 0 0
British Columbia
Country [24] 0 0
Denmark
State/province [24] 0 0
Kopenhagen
Country [25] 0 0
Finland
State/province [25] 0 0
Helsinki
Country [26] 0 0
France
State/province [26] 0 0
Ile De France
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
France
State/province [28] 0 0
Bordeaux
Country [29] 0 0
France
State/province [29] 0 0
Lyon
Country [30] 0 0
Ireland
State/province [30] 0 0
Cork
Country [31] 0 0
Ireland
State/province [31] 0 0
Leinster
Country [32] 0 0
Israel
State/province [32] 0 0
Jerusalem
Country [33] 0 0
Israel
State/province [33] 0 0
Petah Tikva
Country [34] 0 0
Israel
State/province [34] 0 0
Ramat Gan
Country [35] 0 0
Israel
State/province [35] 0 0
Rehovot
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Israel
State/province [36] 0 0
Tel Aviv
Country [37] 0 0
Italy
State/province [37] 0 0
Cremona
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Italy
State/province [38] 0 0
Milano
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Italy
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Napoli
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Italy
State/province [40] 0 0
Roma
Country [41] 0 0
Italy
State/province [41] 0 0
Torino
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Korea, Republic of
State/province [42] 0 0
Seoul
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Serbia
State/province [43] 0 0
Belgrade
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Spain
State/province [44] 0 0
Barcelona
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Valencia
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Puma Biotechnology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the
efficacy and safety of neratinib as monotherapy or in combination with other therapies in
participants with HER (EGFR, HER2) mutation-positive solid tumors.
Trial website
https://clinicaltrials.gov/show/NCT01953926
Trial related presentations / publications
Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018 Feb 8;554(7691):189-194. doi: 10.1038/nature25475. Epub 2018 Jan 31. Erratum in: Nature. 2019 Feb;566(7745):E11-E12.
Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S, Lu J, Shapiro GI, Juric D, Mayer IA, Arteaga CL, de la Fuente MI, Brufksy AM, Spanggaard I, Mau-Sørensen M, Arnedos M, Moreno V, Boni V, Sohn J, Schwartzberg LS, Gonzàlez-Farré X, Cervantes A, Bidard FC, Gorelick AN, Lanman RB, Nagy RJ, Ulaner GA, Chandarlapaty S, Jhaveri K, Gavrila EI, Zimel C, Selcuklu SD, Melcer M, Samoila A, Cai Y, Scaltriti M, Mann G, Xu F, Eli LD, Dujka M, Lalani AS, Bryce R, Baselga J, Taylor BS, Solit DB, Meric-Bernstam F, Hyman DM. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer. Cancer Discov. 2020 Feb;10(2):198-213. doi: 10.1158/2159-8290.CD-19-0966. Epub 2019 Dec 5.
Public notes

Contacts
Principal investigator
Name 0 0
Senior Vice President Clinical Science and Pharmacology
Address 0 0
Puma Biotechnology, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Puma Biotechnology, Inc. Clinical Operations Senior Director
Address 0 0
Country 0 0
Phone 0 0
(424) 248-6500
Fax 0 0
Email 0 0
ClinicalTrials@pumabiotechnology.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01953926