Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02400476




Registration number
NCT02400476
Ethics application status
Date submitted
17/02/2015
Date registered
27/03/2015
Date last updated
6/05/2022

Titles & IDs
Public title
An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Loperamide
Scientific title
An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Loperamide
Secondary ID [1] 0 0
2015-004374-15
Secondary ID [2] 0 0
PUMA-NER-6201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Stage HER2+ Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Neratinib
Treatment: Drugs - Loperamide
Treatment: Drugs - Colestipol
Treatment: Drugs - Budesonide

Experimental: Loperamide - 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Experimental: Budesonide and Loperamide - 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Experimental: Colestipol and Loperamide - 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Experimental: Colestipol with Loperamide as needed - 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Experimental: Neratinib Dose Escalation 1 - 120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Experimental: Neratinib Dose Escalation 2 - 160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.


Treatment: Drugs: Neratinib


Treatment: Drugs: Loperamide


Treatment: Drugs: Colestipol
2 g twice daily with or without food for one 28 day cycle

Treatment: Drugs: Budesonide
9 mg extended release tablets once daily with or without food for 28 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
Timepoint [1] 0 0
From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Secondary outcome [1] 0 0
Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.
Timepoint [1] 0 0
From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Secondary outcome [2] 0 0
Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest
Timepoint [2] 0 0
From first dose of investigational product through 28 days after last dose, up to 15.5 months.

Eligibility
Key inclusion criteria
- Age =18; male or female

- Early breast cancer (stage I-3c)

- Documented HER2+ tumor: HER2 immunohistochemistry (IHC) 3+ or ISH+

- Prior course of adjuvant trastuzumab given >2 weeks and =1 year from enrollment

- No evidence of local/regional recurrence or metastatic disease

- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

- Male patients with female partners of childbearing potential must agree and commit to
use a condom and women of childbearing potential must not be pregnant and must agree
and commit to the use of a highly effective non-hormonal method of contraception

- Left ventricular ejection fraction (LVEF) =50% measured by multiple-gated acquisition
scan (MUGA) or ECHO
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Major surgery < 30 days

- Chemotherapy, investigational agents, other cancer therapy (except hormonal therapy) <
14 days

- Corrected QT Interval (QTc) >0.450 seconds (males) or >0.470 (females) or other active
cardiac disease

- Significant chronic GI disorder with diarrhea as a major symptom

- Active, unresolved infections

- Currently pregnant or breast-feeding

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
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/04/2021
Sample size
Target
Accrual to date
Final
563
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [2] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [3] 0 0
BCRC-WA, Hollywood Private Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Wahroonga
Recruitment postcode(s) [2] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maine
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
Austria
State/province [20] 0 0
Graz
Country [21] 0 0
Austria
State/province [21] 0 0
Innsbruck
Country [22] 0 0
Austria
State/province [22] 0 0
Salzburg
Country [23] 0 0
Austria
State/province [23] 0 0
Vienna
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Villejuif
Country [28] 0 0
Germany
State/province [28] 0 0
Freiburg
Country [29] 0 0
Germany
State/province [29] 0 0
Hamburg
Country [30] 0 0
Germany
State/province [30] 0 0
Kiel
Country [31] 0 0
Germany
State/province [31] 0 0
Offenbach
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Sevilla

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

Ethics approval
Ethics application status

Summary
Brief summary
An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with
Early-Stage HER2+ Breast Cancer Treated with Neratinib and Loperamide or other prophylactic
measures.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02400476
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Chief Scientific Officer
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02400476