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Phase II study to evaluate diarrhoea discontinuations at 3 cycles in patients with early-stage HER2 positive, hormone receptor positive breast cancer treated with neratinib plus loperamide versus neratinib dose escalation plus loperamide administered as needed versus neratinib plus loperamide plus colesevelam.
EU CTIS ID: 2024-514630-21-00
What this study is testing
To evaluate the incidence of neratinib discontinuations due to diarrhoea within the first 3C (1C = 28 days) in patients with early-stage HER2 overexpressed/amplified (HER2+), hormone receptor-positive (HR+) breast cancer who have completed neoadjuvant/adjuvant trastuzumab-based therapy.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Male or female patient ≥18 years of age at signing of informed consent.
- Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, i.e., intrauterine device, bilateral tubal ligation, vasectomized male 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 with his female partner to use a highly effective method of contraception (i.e., 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.
- Recovery (i.e., to Grade 1 or baseline) from all clinically significant adverse events (AEs) related to prior therapies (excluding alopecia, neuropathy, and nail changes).
- Provide written, informed consent to participate in the study and follow the study procedures.
- Histologically confirmed Stage IB through Stage IIIC primary adenocarcinoma of the breast according to the 8th edition of the TNM Classification of Breast Cancer, by the UICC (Union for International Cancer Control). (Clarification note: in patients with surgery as their first treatment approach, the pathological stage will be used; in patients receiving neoadjuvant therapy, the higher staging will be used).
- Documented HER2-positive disease based on local laboratory determination according to ASCO/CAP 2018 criteria.
You likely can't join if
- Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.
- 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 aetiology at baseline); or gastroparesis, dysphagia, or swallowing disorder.
- Clinically active infection with hepatitis B or hepatitis C virus.
- 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.
- Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial.
- Unable or unwilling to swallow tablets.
See the full eligibility criteria
Who can join
- Male or female patient ≥18 years of age at signing of informed consent.
- Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, i.e., intrauterine device, bilateral tubal ligation, vasectomized male 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 with his female partner to use a highly effective method of contraception (i.e., 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.
- Recovery (i.e., to Grade 1 or baseline) from all clinically significant adverse events (AEs) related to prior therapies (excluding alopecia, neuropathy, and nail changes).
- Provide written, informed consent to participate in the study and follow the study procedures.
- Histologically confirmed Stage IB through Stage IIIC primary adenocarcinoma of the breast according to the 8th edition of the TNM Classification of Breast Cancer, by the UICC (Union for International Cancer Control). (Clarification note: in patients with surgery as their first treatment approach, the pathological stage will be used; in patients receiving neoadjuvant therapy, the higher staging will be used).
- Documented HER2-positive disease based on local laboratory determination according to ASCO/CAP 2018 criteria.
- Documented hormone receptor-positive (HR+) disease, defined as oestrogen receptor (ER) and/or progesterone receptor (PR) ≥1% based on local laboratory determination.
- 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).
- 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.
- Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
- 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].
What rules you out
- Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.
- 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 aetiology at baseline); or gastroparesis, dysphagia, or swallowing disorder.
- Clinically active infection with hepatitis B or hepatitis C virus.
- 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.
- Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial.
- Unable or unwilling to swallow tablets.
- Currently receiving chemotherapy, radiation therapy, immunotherapy, or biological therapy for breast cancer (adjuvant endocrine therapy is allowed).
- 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.
- 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.
- QTc interval >0.450 seconds (males) or >0.470 (females) or known history of QTc prolongation or Torsade de Pointes (TdP).
- Screening laboratory assessments outside the following limits: Laboratory Parameters/ Required Limit for Exclusion. Absolute neutrophil count (ANC): < or =1,000/µl (< or =1.0 x 109/L). Platelet count: < or =100,000/µl (< or =100 x 109/L). Hemoglobin: < or =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: Creatinine clearance <30 mL/min (as calculated by Cockcroft-Gault formulaa or Modification of Diet in Renal Disease [MDRD] formulab). a: Cockcroft and Gault, 1976. b: Levey et al, 1999
- Active, unresolved infections.
- 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.
- Currently pregnant or breast-feeding.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.