Three Antidiarrheal Strategies in HER2+/HR+ Early Breast Cancer Patients Treated With Extended Adjuvant Neratinib (DIANER)

A Randomized Phase II Study to Evaluate the Incidence of Discontinuations Due to Diarrhoea at 3 Cycles in Patients With Early-stage HER2-positive (HER2+), Hormone Receptor-positive (HR+) Breast Cancer Treated With Neratinib Plus Loperamide Prophylaxis Versus Neratinib With Initial Dose Escalation Plus PRN Loperamide Prophylaxis Versus Neratinib Plus Loperamide Plus Colesevelam Prophylaxis "DIANER Study"

A Randomized Phase II Study to Evaluate the Incidence of Discontinuations due to Diarrhoea at 3 Cycles in patients with Early-stage HER2-positive (HER2+), Hormone Receptor-positive (HR+) Breast Cancer treated with Neratinib plus Loperamide prophylaxis versus Neratinib with Initial Dose Escalation plus PRN Loperamide prophylaxis versus Neratinib plus Loperamide plus Colesevelam prophylaxis.

Study Overview

• Status: Recruiting
• Conditions: HER2 Positive Breast Cancer; Hormone Receptor Positive; Early-stage Breast Cancer
• Intervention / Treatment: Drug: Neratinib; Drug: Loperamide; Drug: Colesevelam

Detailed Description

This is an international, multicenter, prospective, controlled, randomized, adaptative, phase II study to evaluate the incidence of discontinuations due to diarrhoea within the first 3 cycles in patients with early-stage HER2+ and HR+ breast cancer treated with neratinib plus loperamide prophylaxis for the first 2 cycles versus neratinib with initial 2-week dose escalation plus PRN loperamide versus neratinib and loperamide plus colesevelam prophylaxis for 28 days.

After the preplanned therapy, prophylaxis or treatment for diarrhoea will be given as clinically indicated following the standard of care by the treating physician.

Approximately 315 patients will be enrolled in the study.

All enrolled patients will receive neratinib orally once daily for 13 cycles, continuously. Eligible patients will be randomly assigned in a 1:1:1 ratio to one of the diarrhoea prophylaxis arms, using an interactive response technology (IRT) module within the electronic data capture (EDC) system. Patients will be stratified according to menopausal status (premenopausal versus postmenopausal) and prior anti-HER2 therapy (trastuzumab only versus trastuzumab plus pertuzumab).

Baseline assessments will be performed prior to C1D1 dosing. During the first 3 cycles of treatment, safety data will be collected during the cycle visits. After the first 3 cycles, all patients will enter in a follow-up period to complete approximately 1 year of neratinib treatment. During this follow-up period, safety data will be collected every 3 months. An End-of-Treatment (EOT) Visit is planned on cycle 13 day 28 for all treatment arms (unless patient discontinues earlier), followed by a Safety Follow-up Visit (30 +/-5 days after the last dose of neratinib). This will be the core phase of the study.

After this safety follow-up visit, long term outcome data will be collected for 5 years to address the exploratory objectives. This will be the extended phase of the study. Archived primary tumor tissue (at baseline) and whole blood samples (at baseline, during the treatment and follow-up period, and at disease relapse) will be collected for the exploratory analyses.

Patients are anticipated to participate in the core phase of the study for approximately 1 year to address primary and secondary objectives (28 days for screening, approximately 12 months to complete neratinib treatment, and 30 days for a safety follow-up visit after the last dose of neratinib). Later on patients will continue in the extended phase of the study and will be followed-up for at least 5 years to collect long term outcome data to conduct the exploratory analyses. The approximate duration of the full study is 8 years.

The objectives of the study are indicated below:

Primary objectives:

To evaluate the incidence of neratinib discontinuations due to diarrhoea within the first 3 cycles (1 cycle = 28 days) in patients with early-stage HER2 overexpressed/amplified (HER2+), hormone receptor-positive (HR+) breast cancer who have completed adjuvant trastuzumab-based therapy.

Primary End-point:

Incidence of neratinib discontinuations due to diarrhoea at the end of 3 cycles of neratinib treatment.

Secondary Objectives:

• Incidence and time of neratinib discontinuations due to any treatment-emergent adverse event (TEAE).
• Diarrhoea due to neratinib: incidence, duration, severity, and treatment interventions.
• Incidence of neratinib discontinuation due to any reason.
• Incidence of hospitalisations (overall and for diarrhoea).
• Incidence of TEAEs and serious adverse events (SAEs) and adverse events of special interest (AESIs, ie, hepatic, cardiac, pulmonary, reproductive and developmental).
• Neratinib exposure assessment.
• Determine the effect of study treatment on quality of life, as measured by patient reported outcomes, in all treatment arms.

Secondary End-points:

• Incidence and time to neratinib discontinuations due to any TEAE.
• Incidence, cumulative duration and time to first episode of any diarrhoea and grade 3 or higher diarrhoea.
• Incidence and time to neratinib discontinuation due to any reason.
• Incidence of hospitalisations due to any reason and diarrhoea.
• Incidence of TEAEs and SAEs that included AESIs (i.e. hepatic, cardiac, pulmonary, reproductive and developmental).
• Incidence of Neratinib dose modifications (reductions and dose holds), and dose intensity.
• Systemic therapy-induced diarrhea Assessment Tool (STIDAT), Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer (FACT B) and EuroQol 5 Dimensions 5 Levels (EQ5D-5L) questionnaires.

Exploratory Objectives:

Evaluate minimal residual disease (MRD) and molecular alterations associated with patient outcome, and/or the development of diarrhoea with neratinib.

Exploratory End-points:

Correlation of biomarkers data with patient outcome and safety data.

• Study Type: Interventional
• Enrollment (Estimated): 315
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Project Manager Study Project Manager; Phone Number: +34916592870; Email: inicio_ensayos@geicam.org
• Study Contact Backup: Name: Start-Up Unit Manager Start-Up Unit Manager; Phone Number: +34916592870; Email: inicio_ensayos@geicam.org

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Complejo Hospitalario Universitario A Coruña
  • Albacete, Spain, 02006
    • Recruiting
    • Compejo Hospitalario Universitario de Albacete
  • Badajoz, Spain, 06080
    • Recruiting
    • Hospital Universitario de Badajoz
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital Universitario Santa Creu i Sant Pau
  • Bilbao, Spain, 48013
    • Recruiting
    • Hospital Universitario Basurto
  • Burgos, Spain, 09006
    • Recruiting
    • Hospital Universitario de Burgos
  • Cáceres, Spain, 10003
    • Recruiting
    • Hospital Universitario San Pedro de Alcántara
  • Girona, Spain, 17007
    • Recruiting
    • Institut Català d'Oncologia (ICO) Girona
  • Granada, Spain, 18014
    • Recruiting
    • Hospital Universitario Virgen de Las Nieves
  • Granada, Spain, 18016
    • Recruiting
    • Hospital Universitario Clinico San Cecilio
  • Jaen, Spain, 23007
    • Recruiting
    • Complejo Hospitalario de Jaén
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
  • Santa Cruz De Tenerife, Spain, 38010
    • Recruiting
    • Hospital Universitario Nuestra Señora de Candelaria
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Del Rocio
  • Sevilla, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen De La Macarena
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Quirónsalud Sagrado Corazón
  • Toledo, Spain, 45007
    • Recruiting
    • Hospital Universitario de Toledo
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politecnico La Fe
  • Valencia, Spain, 46009
    • Recruiting
    • Fundación Instituto Valenciano de Oncología
  • Valencia, Spain, 46015
    • Recruiting
    • Hospital Universitario Arnau de Vilanova de Valencia
  • Valencia, Spain, 46018
    • Recruiting
    • Consorcio Hospital General Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Recruiting
    • Hospital Universitario Miguel Servet
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Recruiting
      • Hospital General Universitario de Elche
  • Andalucía
    • Málaga, Andalucía, Spain, 29603
      • Recruiting
      • Hospital Costa del Sol
  • Aragón
    • Zaragoza, Aragón, Spain, 50009
      • Recruiting
      • Hospital Clínico Universitario Lozano Blesa
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • Institut Català d'Oncología (ICO) L'Hospitalet
    • Manresa, Barcelona, Spain, 08243
      • Recruiting
      • Althaia Xarxa Asistencial de Manresa
    • Mataró, Barcelona, Spain, 08304
      • Recruiting
      • Hospital de Mataró
  • Castellón
    • Castellón De La Plana, Castellón, Spain, 12002
      • Recruiting
      • Consorcio Hospitalario Provincial de Castellon
  • Castilla-León
    • Valladolid, Castilla-León, Spain, 47003
      • Recruiting
      • Hospital Clínico Universitario de Valladolid
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Recruiting
      • Hospital General Universitario Dr. Balmis
  • Cádiz
    • Cadiz, Cádiz, Spain, 11009
      • Recruiting
      • Hospital Universitario Puerta Del Mar
    • Jerez De La Frontera, Cádiz, Spain, 11407
      • Recruiting
      • Hospital Universitario de Jeréz De La Frontera
  • Galicia
    • A Coruña, Galicia, Spain, 15009
      • Recruiting
      • Centro Oncológico de Galicia
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Recruiting
      • Hospital Universitario Fundacion Alcorcon
    • Fuenlabrada, Madrid, Spain, 28942
      • Recruiting
      • Hospital Universitario de Fuenlabrada
    • Leganés, Madrid, Spain, 28911
      • Recruiting
      • Hospital Universitario Severo Ochoa
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Puerta de Hierro Majadahonda
    • Móstoles, Madrid, Spain, 28935
      • Recruiting
      • Hospital Universitario de Móstoles
    • Parla, Madrid, Spain, 28981
      • Recruiting
      • Hospital Universitario Infanta Cristina
    • San Sebastián de los Reyes, Madrid, Spain, 28702
      • Recruiting
      • Hospital Universitario Infanta Sofía
  • Mallorca
    • Palma De Mallorca, Mallorca, Spain, 07120
      • Recruiting
      • Hospital Universitario Son Espases
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clinico Universitario Virgen de La Arrixaca
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36213
      • Recruiting
      • Hospital Alvaro Cunqueiro
  • Tarragona
    • Reus, Tarragona, Spain, 43204
      • Recruiting
      • Hospital Universitario San Joan de Reus
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Recruiting
      • Hospital Universitario Cruces
    • Usansolo, Vizcaya, Spain, 48960
      • Recruiting
      • OSI Barrualde-Galdakao (Hospital Galdakao-Usansolo)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients are eligible to be enrolled in the study only if they meet all of the following criteria:

1. Male or female patient ≥18 years of age at signing of informed consent.
2. Histologically confirmed Stage I B through Stage III C primary adenocarcinoma of the breast.
3. Documented HER2-positive disease based on local laboratory determination according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 criteria.
4. Documented HR+ disease, defined as oestrogen receptor (ER) and/or progesterone receptor (PR) ≥1% based on local laboratory determination.
5. Patients must have completed prior neoadjuvant/adjuvant trastuzumab-based therapy (eg, trastuzumab-based treatments including trastuzumab-emtansine [T-DM1]) or experienced side effects that resulted in early discontinuation of trastuzumab-based therapy that have since resolved (pertuzumab therapy is accepted but not mandatory).
6. The last dose of trastuzumab-based therapy must have been given to the patient >2 weeks and ≤1 year (365 days) before first dose of neratinib.
7. Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
8. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
9. Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause. [Women are considered postmenopausal if they are ≥ 12 months without menses, in the absence of endocrine or anti-endocrine therapies].
10. Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 30 days after the last dose of the medicinal products. Male patient with female partner of childbearing potential must agree and commit to use condom, and the female partner must agree and commit to use a highly effective method of contraception (ie, any of the above methods, or for females, hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of medicinal products.
11. Recovery (ie, to Grade 1 or baseline) from all clinically significant AEs related to prior therapies (excluding alopecia, neuropathy, and nail changes).
12. Provide written, informed consent to participate in the study and follow the study procedures.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.
2. Currently receiving chemotherapy, radiation therapy, immunotherapy, or biological therapy for breast cancer (adjuvant endocrine therapy is allowed).
3. Major surgery within <30 days of starting treatment or received chemotherapy, investigational agents, or other cancer therapy <14 days prior to the initiation of investigational products.
4. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrolment, or ventricular arrhythmia.
5. Corrected QT interval (QTc) interval >0.450 seconds (males) or >0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP).

6. Screening laboratory assessments outside the following limits:

   Absolute neutrophil count (ANC) ≤1,000/μl (≤1.0 x 109/L), Platelet count ≤100,000/μl (≤100 x 109/L), Hemoglobin ≤9 g/dL, Total bilirubin >1.5 x institutional upper limit of normal (ULN) (in case of known Gilbert's syndrome, <2 x ULN is allowed), Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x institutional ULN, Creatinine clearance <30 mL/min (as calculated by Cockcroft-Gault formula a or Modification of Diet in Renal Disease (MDRD) formula).

7. Active, unresolved infections.
8. Patients with a second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Patients with other non-mammary malignancies must have been disease-free for at least 5 years.
9. Currently pregnant or breast-feeding.
10. Significant chronic gastrointestinal disorder with diarrhoea as a major symptom (eg, Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 5.0 [CTCAE v.5.0] diarrhoea of any etiology at baseline); or gastroparesis, dysphagia, or swallowing disorder.
11. Clinically active infection with hepatitis B or hepatitis C virus.
12. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investigator's judgment, make the patient inappropriate for this study.
13. Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial.
14. Unable or unwilling to swallow tablets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Neratinib 240 mg (six 40mg tablets) orally once daily for 13 cycles (C) (1 C = 28 days), unless patient discontinues earlier.; Mandatory loperamide 4 mg (2 tablets/capsules) orally, 3 times a day (total 12 mg a day) starting Day (D) 1 of neratinib and for the first 14 days. Then, 4 mg (2 tablets/capsules) orally, 2 times a day (total 8 mg a day) until the end of C2 (D56); thereafter, loperamide will be administered PRN (without exceeding 16 mg per day).	Drug: Neratinib; Neratinib orally once daily for 13 cycles, unless patient discontinues earlier.; Other Names: Nerlynx; Drug: Loperamide; Loperamide orally.; Other Names: Sindiar
Experimental: Arm B; Neratinib 120 mg 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 for 13 cycles inclusive, until cycle 13 day 28 (unless patient discontinues earlier).; Loperamide to be administered PRN only (without exceeding 16 mg per day).	Drug: Neratinib; Neratinib orally once daily for 13 cycles, unless patient discontinues earlier.; Other Names: Nerlynx; Drug: Loperamide; Loperamide orally.; Other Names: Sindiar
Experimental: Arm C; Neratinib 240 mg (six 40-mg tablets) orally once daily for 13 C, unless patient discontinues earlier.; Mandatory loperamide 4 mg (2 tablets/capsules) orally, 3 times a day (total 12 mg a day) for the first 14 days. After the first 14 days, 4 mg (2 tablets/capsules) orally, 2 times a day (total 8 mg a day) to complete a total of 28 days.; Mandatory colesevelam 1,875 mg (three 625-mg capsules orally), 2 times a day for the first month (28 days). After day 28, any prophylaxis or treatment for diarrhoea could be administered PRN, if loperamide not to exceed 16 mg per day.	Drug: Neratinib; Neratinib orally once daily for 13 cycles, unless patient discontinues earlier.; Other Names: Nerlynx; Drug: Loperamide; Loperamide orally.; Other Names: Sindiar; Drug: Colesevelam; Colesevelam capsules orally, 2 times a day for the first month (28 days).; Other Names: Cholestagel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of neratinib discontinuations due to diarrhoea at the end of 3 cycles (1 cycle= 28 days) of neratinib treatment.	The proportion of patients who discontinue the treatment with neratinib due to diarrhoea within this time period.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of neratinib discontinuations due to any TEAE (treatment-emergent adverse event).	The proportion of patients who discontinue the treatment of neratinib at any time due to any TEAE. TEAE are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.	Up to 13 months
Time to neratinib discontinuations due to any TEAE (treatment-emergent adverse event).	The time from the start of neratinib therapy to the discontinuation due to any TEAE.	Up to 13 months
Incidence of diarrhoea of any grade/grade 3 or higher.	The proportion of patients with at least one TEAE of diarrhoea of any grade/grade 3 or higher coded and graded by the investigator according to the NCI-CTCAE version 5.0.	Up to 13 months
Cumulative duration of diarrhoea (Grade 2/3/4).	The time from the diagnosis of each of the different diarrhoea Grades 2 or 3 or 4 coded and graded by the investigator according to the NCI-CTCAE version 5.0 to the time of change to a different grade of this adverse event.	Up to 13 months
Time to first episode of diarrhoea.	The time from the start of neratinib therapy to the first episode of diarrhoea of any grade, whichever occurs first.	Up to 13 months
Incidence of neratinib discontinuation (for any reason).	The proportion of patients who discontinued neratinib early (before 1 year of therapy).	Up to 13 months
Time to neratinib discontinuation/neratinib treatment duration.	The time from the start of neratinib to the last dose of neratinib.	Up to 13 months
Incidence of hospitalisations due to any reason and diarrhoea.	The proportion of patients who have a hospitalisation during the treatment with neratinib or 30 days after the last dose.	Up to 13 months
Incidence of TEAEs and SAEs that include AESIs (ie, hepatic, cardiac, pulmonary, reproductive and developmental).	The proportion of patients in which those events are observed.	Up to 13 months
Cumulative dose of neratinib.	The total dose of neratinib administered during the study.	Up to 13 months
Neratinib dose intensity.	The cumulative dose of neratinib divided by the neratinib treatment duration.	Up to 13 months
Neratinib relative dose intensity.	The dose intensity divided by 240 mg.	Up to 13 months
Patient reported outcomes (PRO) of health related quality of life measured by FACT B.	PRO of health related quality of life will be assessed using the FACT-B questionnaire. The FACT-B is a 36-item questionnaire composed of five multi-item functional subscales: physical well-being, social/family well-being, emotional well-being, functional well-being and a subscale related with the breast cancer and its treatment. The questionnaire employs 5 points Likert scales with responses from "not at all" to "very much". The total score is obtained from the sum of the score on each subscale. Patients will complete a questionnaire at cycle 1 day 1 (before the first dose of neratinib and anti-diarrhoeal therapy), on day 1 of cycles 2, 3, 4, 7 and 10 and at the End of Treatment Visit.	Up to 13 months
Patient reported outcomes (PRO) of health related quality of life measured by EQ5D-5L	To be assessed using the EQ5D-5L questionnaire, a standardized instrument for measuring generic health status. It has 2 components: health state description: measured in terms of 5 dimensions; mobility (person's walking ability), self-care (ability to wash or dress by oneself), usual activities (work, study, housework, family or leisure activities), pain/discomfort (how much pain or discomfort they have), and anxiety/depression (how anxious or depressed they are). The number of levels of severity is 5; having no problems, slight problems, moderate problems, severe problems and being unable to do/extreme problems. The respondents self-rate their level of severity for each dimension.; Evaluation: It also includes a visual analogue scale, EQ VAS, which records patient's self-rated health on a scale from 0 (worst imaginable) to 100 (best imaginable). To be completed at day 1 of cycles 1, 2, 3, 4, 7 and 10 and at the End of Treatment Visit.	Up to 13 months
Patient reported outcomes (PRO) of health related quality of life measured by Systemic Therapy-Induced Diarrhea Assessment Test (STIDAT)	PRO of health related quality of life will be assessed using the STIDAT questionnaire. The STIDAT is a questionnaire that was developed using the FDA iterative process for patient-reported outcomes in which patients define diarrhoea based on presence of watery stool. The STIDAT assess patient's perception of having diarrhoea, daily number of bowel movements, daily number of diarrhoea episodes, antidiarrheal medication use, the presence of urgency, abdominal pain, abdominal spasms or fecal incontinence, patient's perception of diarrhoea severity, and QoL. Patients will complete the instrument at cycle 1 day 1 (before the first dose of neratinib and anti-diarrhoeal therapy), on day 1 of cycles 2, 3, 4, 7, 10 and at the End of Treatment Visit.	Up to 13 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal residual disease (MRD)	Correlation of biomarkers data with patient outcome and safety data These analysis will be performed in the biomarker population. Given a relapse rate of around 10%, we anticipate that approximately 150-200 patients would be sufficient to explore the prognostic value of the MRD assessed on circulating tumor DNA and the correlation of the molecular and clinical relapse.	Up to 13 months

Collaborators and Investigators

• Sponsor: Spanish Breast Cancer Research Group
• Collaborators: Pierre Fabre Laboratories; Puma Biotechnology, Inc.
• Investigators: Study Director: Study Director Study Director, Hospital General Universitario Gregorio Marañon; Study Director: Study Director Study Director, Insititut Català d'Oncologia de L'Hospitalet

Publications and helpful links

Helpful Links

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Estimated): March 25, 2025
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Neratinib; HER2 positive; Early-stage Breast Cancer; Hormone Receptor positive; Loperamide prophylaxis; Colesevelam prophylaxis; Incidence of Discontinuations due to Diarrhoea
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride; Loperamide; Antidiarrheals
• Other Study ID Numbers: GEICAM/2018-06; 2019-001559-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No