Ignite Creation Date:
2024-05-06 @ 5:17 PM
Last Modification Date:
2024-10-26 @ 2:25 PM
Study NCT ID:
NCT05252988
Status:
RECRUITING
Last Update Posted:
2023-12-15
First Post:
2022-02-02
Brief Title:
Three Antidiarrheal Strategies in HER2HR Early Breast Cancer Patients Treated With Extended Adjuvant Neratinib
Sponsor:
Spanish Breast Cancer Research Group
Organization:
Spanish Breast Cancer Research Group
Study Overview
Official Title:
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
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DIANER
Brief Summary:
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
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 111 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 overexpressedamplified 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 ie 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 andor the development of diarrhoea with neratinib
Exploratory End-points
Correlation of biomarkers data with patient outcome and safety data
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 111 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 overexpressedamplified 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 ie 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 andor the development of diarrhoea with neratinib
Exploratory End-points
Correlation of biomarkers data with patient outcome and safety data
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2019-001559-38 | EUDRACT_NUMBER | None | None |