Trial Title:
Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab
NCT ID:
NCT05744375
Condition:
Locally Advanced Breast Cancer
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Trastuzumab
Trastuzumab deruxtecan
Conditions: Keywords:
Trastuzumab deruxtecan
HER2-positive
Advanced Breast Cancer
Metastatic Breast Cancer
resistant to prior (neo) adjuvant anti-HER2 therapy.
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Trastuzumab deruxtecan
Description:
All patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV
every 3 weeks (± 3 days).
The subject's weight at baseline will be used to calculate the initial dose. If during
the course of treatment the subject's weight changes by ± 10% of the baseline weight, the
subject's dose will be recalculated based on the subject's updated weight.
Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD),
informed consent withdrawal, or other discontinuation criterion is met.
Arm group label:
Trastuzumab deruxtecan (T-DXd)
Other name:
Enhertu
Summary:
The goal of this national, multicenter single arm phase II clinical trial is to study the
efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd)
in HER2-positive locally advanced or metastatic breast cancer (MBC) patients resistant to
trastuzumab plus pertuzumab plus taxane due to early relapse.
The main questions it aims to answer are:
- To evaluate the antitumor activity of T-DXd in the first-line treatment of
HER2-positive breast cancer patients resistant to trastuzumab-pertuzumab based
therapy.
- To assess other efficacy measures.
- To evaluate safety and tolerability in all patients enrolled in the study.
- To evaluate health-related quality of life (HRQoL). Forty-one evaluable patients
will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3
days). Patients will receive T-DXd until unacceptable toxicity, progressive disease,
informed consent withdrawal, or other discontinuation criterion is met.
Detailed description:
This is a national, multicenter single arm phase II clinical trial to study the efficacy,
safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in
HER2-positive locally advanced or MBC patients resistant to trastuzumab plus pertuzumab
plus taxane due to early relapse.
Eligible patients will be enrolled and treated with T-DXd 5.4 mg/kg IV every 3 weeks.
The T-DXd dose will be recalculated in the event that patients experience body weight
variations greater than 10% during the treatment period.
All patients enrolled will receive study therapy until radiographic or symptomatic
progressive disease, unacceptable toxicity or withdraw of the informed consent, whatever
occurs first.
Study population:
HER2-positive locally advanced or MBC patients who have not received prior chemotherapy
or HER2 targeted therapy for advanced disease and with a Disease-Free Interval (DFI) of
<12 months from the end of prior (neo)adjuvant anti-HER2 therapy.
Study Duration: The start date of the study is the date of the first site activation.
Recruitment period will occur during approximately 24 months from the first patient in.
The end date of the study is the date of the last visit of the last patient (LPLV),
including follow-up. The duration of the study will be approximately 68 months from the
first patient in.
Performing exploratory objectives will be independent of the date of the end of the
study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written and signed informed consent obtained prior to any study-specific procedure.
2. Male or female patients of at least 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
4. Life expectancy ≥ 12 weeks.
5. Recurrent breast cancer that is unresectable locally advanced or metastatic.
6. Pathologically documented HER2-positive status by local laboratory determination,
preferably on the most recent available Formalin-fixed paraffin-embedded (FFPE)
tumor sample, according to the American Society of Clinical Oncology (ASCO)/College
of American Pathologists (CAP) international guidelines valid at the time of the
assay. In case of discordance in HER2 status in different biopsies, the result from
the most recent biopsy will be used.
7. Pathologically documented Hormone Receptor (HR)-positive or -negative by local
laboratory determination, preferably on the most recent available FFPE tumor sample,
and according to ASCO/CAP international guidelines valid at the time of the assay.
In case of discordance in HR status in different biopsies, the result from the most
recent biopsy will be used.
8. Prior anti-HER2 based therapy (with trastuzumab plus pertuzumab plus taxane with or
without trastuzumab-emtansine) in the (neo)adjuvant setting with a relapse while on
therapy or within 12 months from the end of last anti-HER2 therapy.
9. Measurable disease assessed by the investigator based on RECIST version 1.1.
10. Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated
acquisition scan (MUGA) or echocardiogram (ECHO).
11. Adequate organ and marrow function defined as follows:
1. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 (1.5x109/L).
2. Platelet count ≥ 100,000/mm3 (100x109/L).
3. Hemoglobin ≥ 9g/dL (90g/L).
4. Creatinine clearance ≥ 30 mL/min as calculated using the standard method for
the institution.
5. Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver
metastases or < 3 × ULN in the presence of documented Gilbert's syndrome
(unconjugated hyperbilirubinemia) or liver metastases at baseline.
6. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3.0 x
ULN (< 5.0 × ULN in participants with liver metastases).
7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases
are present).
8. Serum albumin ≥ 2.5 g/dL
12. International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) ≤ 1.5 x ULN.
13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests and other study procedures.
14. Negative serum pregnancy test with a sensitivity of at least 25 milliInternational
Units per milliliter of urine (mIU/mL) (unless permanent previous sterilization
procedure such as bilateral salpingectomy, bilateral oophorectomy, or complete
hysterectomy) for premenopausal women, and for women who have experienced menopause
onset < 12 months prior to first dose of therapy.
Exclusion Criteria:
1. Prior chemotherapy or HER2-targeted therapy for locally advanced or MBC (one prior
endocrine therapy regimen for MBC without concurrent anti-HER2 therapy or
radiotherapy is allowed).
2. Ineligible for treatment with T-DXd.
3. Any substance abuse or other medical conditions that, in the investigator's opinion,
may interfere with patient's participation or study results.
4. Patients with spinal cord compression, leptomeningeal disease or clinically active
central nervous system (CNS) metastases. Participants with clinically inactive brain
metastases or treated brain metastases that are no longer symptomatic, and no
needing corticosteroids or anticonvulsants may be enrolled in the study.
5. Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected
ILD/pneumonitis that cannot be ruled out by imaging at screening.
6. Lung criteria:
1. Lung-specific intercurrent clinically significant illnesses including, but not
limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within
three months of the study enrollment, severe asthma, severe Chronic obstructive
pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.).
2. Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid
arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a
suspicion of pulmonary involvement at the time of screening. Full details of
the disorder should be recorded in the electronic Case Report Form (eCRF) for
patients who are enrolled in the study.
3. Prior pneumonectomy.
7. Medical history of myocardial infarction within 6 months before registration,
symptomatic congestive heart failure (CHF), troponin levels consistent with
myocardial infarction as defined according to American College of Cardiologists
(ACC) guidelines, unstable angina, or serious cardiac arrhythmia requiring
treatment. QT interval corrected using Fridericia's formula (QTcF) > 470 msec
(females) or > 450 msec (males) based on average of the screening triplicate 12-lead
ECG.
8. History of active primary immunodeficiency, known Human Immunodeficiency Virus
(HIV), active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
9. Patients who received before treatment starts:
1. Any investigational agent within 4 weeks.
2. Chemotherapy within a period of time that is shorter than the cycle duration
used for that treatment (e.g. < 3 weeks for fluorouracil, doxorubicine,
epirubicin or < 1 week for weekly chemotherapy).
3. Targeted therapy (e.g., antibodies): up to 4 weeks prior to starting study
treatment.
4. Endocrine therapy: tamoxifen or aromatase inhibitor within 2 weeks prior to
starting study treatment.
5. Radiotherapy within 2 weeks prior to starting study treatment. Patients who
received prior radiotherapy to >25% of bone marrow are not eligible regardless
of when it was administered.
6. Major surgery or other anti-cancer therapy not previously specified within 4
weeks prior to starting study treatment.
In any case, resolution of all acute toxic effects of prior anti-cancer therapy or
surgical procedures to NCI-CTCAE version 5.0 grade ≤ 1 (except alopecia or other
toxicities not considered a safety risk for the patient at investigator´s
discretion) is mandatory.Patients may be enrolled with chronic, stable grade 2
toxicities (defined as no worsening to > grade 2 for at least 3 months prior to
enrollment and managed with standard of care treatment) that the investigator deems
related to previous anticancer therapy, such as: chemotherapy-induced neuropathy or
fatigue and immunotherapy-induced toxicities (e.g. endocrinopathies as
hypothyroidism/hyperthyroidism, type 1 diabetes, hypoglycemia, adrenal
insufficiency, adrenalitis and skin hypopigmentation [vitiligo]).
10. Have a diagnosis of any other malignancy within 3 years prior to inclusion, except
for adequately resected non-melanoma skin cancer, curatively treated in-situ
disease, other solid tumors curatively treated and contralateral breast cancer.
11. Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd.
12. Prior treatment with T-DXd or allergic reaction to trastuzumab.
13. Patient is pregnant or breastfeeding or planning to become pregnant within the
projected duration of the trial, starting at screening and through 7 months after
the last dose of the study treatment. Male patients whose partners plan to become
pregnant within the duration of the trial, starting at screening and through 4
months after the last dose of the study treatment.
✓ For premenopausal women it is necessary an agreement to remain complete abstinent
or use single or combined non-hormonal contraceptive methods that result in a
failure rate of < 1% per year during the treatment period and for at least 7 months
after the last dose of study treatment.
- Examples of non-hormonal contraceptive methods with a failure rate of < 1% per
year include bilateral tubal litigation, male sterilization, and certain
intrauterine devices (provided coils are copper banded).
- Alternative, two methods (e.g. two barrier methods such as a condom and a
cervical cap or combined with estrogen and progestogen) may be combined to
achieve a failure rate of < 1% per year. Barrier methods must always be
supplemented with the use of a spermicide.
Female patients must not donate, or retrieve for their own use, ova from the time of
enrollment and throughout the study treatment period, and for at least 7 months
after the final study drug administration. They should refrain from breastfeeding
throughout this time. Preservation of ova may be considered prior to enrollment in
this study.
✓ For men it is necessary an agreement to remain complete abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, and to refrain from
donating sperm during the same period, as defined below with female partners of
childbearing potential or pregnant female partners, men must remain abstinent or use
a condom during the treatment period and for at least 4 months after the last dose
of study treatment to avoid exposing the embryo.
Abstinence is only acceptable if it is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable methods
of contraception.
14. Uncontrolled intercurrent illness including uncontrolled infection requiring
intravenous (IV) antibiotics, antivirals, or antifungals.
15. Has substance abuse or any other medical/psychological conditions that may, in the
opinion of the investigator, interfere with the patient's participation in the
clinical study or evaluation of the clinical study results.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Universitario de Jeréz De La Frontera
Address:
City:
Cádiz
Zip:
11407
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario de Jaén
Address:
City:
Jaén
Zip:
23007
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Marqués de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario de Fuenlabrada
Address:
City:
Fuenlabrada
Zip:
28942
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Puerta de Hierro de Majadahonda
Address:
City:
Majadahonda
Zip:
28222
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Son Espases
Address:
City:
Palma De Mallorca
Zip:
07120
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Galdakao-Usansolo
Address:
City:
Galdakao
Zip:
48960
Country:
Spain
Status:
Recruiting
Facility:
Name:
Complejo Hospitalario Universitario A Coruña (CHUAC)
Address:
City:
A Coruña
Zip:
15006
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital San Juan de Alicante
Address:
City:
Alicante
Zip:
03550
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario de Badajoz
Address:
City:
Badajoz
Zip:
06080
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital del Mar
Address:
City:
Barcelona
Zip:
08003
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario San Pedro de Alcántara
Address:
City:
Cáceres
Zip:
10003
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Clínico San Cecilio
Address:
City:
Granada
Zip:
18016
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Arnau de Vilanova de Lleida
Address:
City:
Lleida
Zip:
25198
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital General Universitario Gregorio Marañón
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Ramón y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Virgen del Rocío
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Start date:
September 28, 2023
Completion date:
March 1, 2029
Lead sponsor:
Agency:
Spanish Breast Cancer Research Group
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Spanish Breast Cancer Research Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05744375
http://www.geicam.org
