TriangleNCT02400476 · CITED IN SOURCE DOCUMENTS
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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2022-05-06
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.
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.
Participant flow
Baseline characteristics
Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.
Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.
- intervention Names
- Drug: Neratinib
- Drug: Loperamide
- label
- Loperamide
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Neratinib
- Drug: Loperamide
- Drug: Budesonide
- label
- Budesonide and Loperamide
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Neratinib
- Drug: Loperamide
- Drug: Colestipol
- label
- Colestipol and Loperamide
- type
- EXPERIMENTAL
- description
- 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.
- intervention Names
- Drug: Neratinib
- Drug: Loperamide
- Drug: Colestipol
- label
- Colestipol with Loperamide as needed
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Neratinib
- Drug: Loperamide
- label
- Neratinib Dose Escalation 1
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Neratinib
- Drug: Loperamide
- label
- Neratinib Dose Escalation 2
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Budesonide and Loperamide
- Colestipol and Loperamide
- Colestipol with Loperamide as needed
- Loperamide
- Neratinib Dose Escalation 1
- Neratinib Dose Escalation 2
- name
- Neratinib
- other Names
- Nerlynx
- type
- DRUG
- arm Group Labels
- Budesonide and Loperamide
- Colestipol and Loperamide
- Colestipol with Loperamide as needed
- Loperamide
- Neratinib Dose Escalation 1
- Neratinib Dose Escalation 2
- name
- Loperamide
- type
- DRUG
- arm Group Labels
- Colestipol and Loperamide
- Colestipol with Loperamide as needed
- description
- 2 g twice daily with or without food for one 28 day cycle
- name
- Colestipol
- type
- DRUG
- arm Group Labels
- Budesonide and Loperamide
- description
- 9 mg extended release tablets once daily with or without food for 28 days
- name
- Budesonide
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SEQUENTIAL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 563
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- The primary objective of this study is to characterize the percentage of patients with Grade 3 or higher diarrhea in patients with early-stage HER2 overexpressed/amplified (HER2+) breast cancer treated with neratinib when administered with intensive loperamide prophylaxis, after prior treatment with trastuzumab. Grade 3: Increase of \>=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
- measure
- Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
- time Frame
- From first dose of investigational product through 28 days after last dose, up to 15.5 months.
- secondary Outcomes
- description
- Assess the percentage of patients with diarrhea after the administration of an anti-inflammatory agent, a bile acid sequestrant, or following two different dose-escalation regimens of neratinib, by maximum CTC grade. Grade 1: an increase of \<4 stools per day over baseline; mild increase in ostomy output compared to baseline. Grade 2: Increase of 4 - 6 stools per day over baseline; moderate increase in ostomy output compared to baseline. Grade 3: Increase of \>=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
- measure
- Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.
- time Frame
- From first dose of investigational product through 28 days after last dose, up to 15.5 months.
- description
- Assess the percentage of patients with serious adverse events (SAEs) and other adverse events of special interest (AESI). AESIs were selected based on the known safety profile of neratinib as well as typical key body system toxicity concerns generally reviewed for any new drug. These AESIs were grouped into the following categories: gastrointestinal toxicity (diarrhea and stomatitis), hepatotoxicity, pulmonary toxicity (interstitial lung disease), cardiac toxicity (LVEF decreased), and dermatologic toxicity (rash and nail disorders). The AESIs were analyzed by searching the clinical database for all TEAEs and SAEs using either Standardized MedDRA Queries (SMQs) or, if an applicable SMQ did not exist, a Sponsor-defined list of MedDRA preferred terms.
- measure
- Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest
- time Frame
- From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Full study description
- 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.
- detailed Description
- This is an open-label, Phase 2 study that will investigate the incidence and severity of diarrhea in early-stage HER2+ breast cancer patients receiving neratinib with loperamide, alone and in combination with an anti-inflammatory treatment or a bile acid sequestrant treatment, or neratinib dose escalation, who have previously undergone a course of trastuzumab therapy in the adjuvant setting. Patients will receive: * Neratinib 240 mg orally once daily with food for thirteen 28-day cycles. * Loperamide daily for two 28-day cycles and then as needed. * Amendment 3, an anti-inflammatory treatment for one cycle and loperamide to be administered daily for two 28-day cycles and then as needed. Closed to enrollment. * Amendment 4, colestipol for one cycle and loperamide to be administered one cycle and then as needed. Closed to enrollment. * Amendment 5, colestipol for one cycle and loperamide as needed. Closed to enrollment. * Amendment 6/6.1, 120 mg neratinib for Week 1 (C1D1-C1D7), followed by 160 mg neratinib for Week 2 (C1D8-C1D14), followed by 240 mg neratinib for Week 3 and thereafter (C1D15 to end of treatment). Loperamide as needed. Closed to enrollment. * Amendment 7/7.1, 160 mg neratinib for the first 2 weeks (C1D1 - C1D14), followed by 200 mg neratinib for the next 2 weeks (C1D15 - C1D28), followed by 240 mg neratinib thereafter (C2D1 to end of treatment). Loperamide as needed.
Source references
- references
- citation
- Chan A, Ruiz-Borrego M, Marx G, Chien AJ, Rugo HS, Brufsky A, Thirlwell M, Trudeau M, Bose R, Garcia-Saenz JA, Egle D, Pistilli B, Wassermann J, Cheong KA, Schnappauf B, Semsek D, Singer CF, Foruzan N, DiPrimeo D, McCulloch L, Hurvitz SA, Barcenas CH. Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer. Breast. 2023 Feb;67:94-101. doi: 10.1016/j.breast.2022.12.003. Epub 2022 Dec 14.
- pmid
- 36702070
- type
- DERIVED
- citation
- Barcenas CH, Hurvitz SA, Di Palma JA, Bose R, Chien AJ, Iannotti N, Marx G, Brufsky A, Litvak A, Ibrahim E, Alvarez RH, Ruiz-Borrego M, Chan N, Manalo Y, Kellum A, Trudeau M, Thirlwell M, Garcia Saenz J, Hunt D, Bryce R, McCulloch L, Rugo HS, Tripathy D, Chan A; CONTROL Study Investigators. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Ann Oncol. 2020 Sep;31(9):1223-1230. doi: 10.1016/j.annonc.2020.05.012. Epub 2020 May 25.
- pmid
- 32464281
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- r Dizziness 14 0.3 0 10 0.6 0 Renal and urinary disorders Renal impairment* 7 2 0.3 1 0 0.3 Dysuria 4.6 0 0 1.9 0 0 Management of Diarrhea CONTROL The CONTROL (NCT02400476) study was a multicenter, open-label, multi-cohort trial evaluating patients with early-stage HER2-positive breast cancer treated with NERLYNX 240 mg daily for
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Preserved source evidence · Not medical advice