Trial Title:
HR+/HER2- Advanced or Metastatic Breast Cancer Patients Treated With Sacituzumab Govitecan
NCT ID:
NCT06236269
Condition:
Breast Cancer Stage IV
Conditions: Official terms:
Breast Neoplasms
Sacituzumab govitecan
Conditions: Keywords:
sacituzumab govitecan
breast cancer
CelTIL
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sacituzumab Govitecan
Description:
Sacituzumab Govitecan 10 mg/kg will be administrad intravenously (IV) on Days 1, 8 of a
21-day cycle
Arm group label:
Sacituzumab Govitecan
Other name:
Trodelvy
Summary:
This is an open-label, single arm, non-randomized, multicenter phase II study for the
identification of predictive biomarkers of sacituzumab govitecan benefit and the
understanding of key resistance mechanisms in HR+/HER2- advanced/metastatic breast cancer
patients
Detailed description:
This study will include patients with HR+/HER2- advanced/metastatic breast cancer who
have progressed on prior endocrine therapy and CDK4/6i and who have received up to 1
prior regimen of chemotherapy or ADC for metastatic breast canncer.
The primary objective is to evaluate the change in the CelTIL score, a combined biomarker
based on stromal tumor-infiltrating lymphocytes and tumor cellularity, as surrogate of
treatment response after one dose of sacituzumab govitecan (SG).
Patients who fulfil all eligibility criteria will start SG at 10 mg/kg as an IV infusion
on Days 1 and 8 of a 21-day cycle. SG will be administered continuously until progression
of the disease, unacceptable toxicity, investigator's decision, withdrawal of consent, or
other reasons described in the protocol.
Tumor tissue (newly obtained) will be sent to a central laboratory. After 2 weeks(14-21
days) of treatment a new biopsy of the same lesion will be performed. Tumor biopsy will
be also performed at disease progression / EoT. In addition, blood samples (for ctDNA)
will be collected at C1D1, C2D1 and at progression / EoT for exploratory objectives.
Imaging will be performed prior to day 1 of treatment and target and non-target lesions
will be identified as per RECIST 1.1. Tumor assessments will be performed every 9 weeks
until the start of a new anti-cancer therapy, withdrawal of consent, progression of
disease, death, or the end of the study, whichever occurs first. Tumor assessments will
be performed on the specified schedule regardless of treatment delays. Tumor response
will be assessed as per RECIST v.1.1.
Safety assessments will include the incidence, nature, and severity of AEs and laboratory
abnormalities graded per the NCI CTCAE v.5.0. Laboratory safety assessments will include
the regular monitoring of hematology, blood chemistry and pregnancy test.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provision of signed and dated, written informed consent form prior to any mandatory
study specific procedures, sampling, and analyses.
2. Patients must be male or female (pre/peri or postmenopausal) ≥ 18 years of age.
3. ECOG performance status of 0 or 1(see Appendix 1).
4. Histologically or cytologically confirmed breast cancer with evidence of locally
advanced disease, not amenable to resection or radiation therapy with curative
intent or metastatic disease.
5. HR+/HER2- BC by local testing, not amenable to surgical therapy will be enrolled in
this study.
1. HER2 negativity is defined as either of the following by local laboratory
assessment: IHC 0, IHC 1+ or IHC2+/in situ hybridization (ISH) negative as per
the most recent American Society of Clinical Oncology (ASCO)-College of
American Pathologists Guideline (CAP) guideline. If a patient has had multiple
HER2 results after metastatic disease, the most recent test result prior
screening period will be used to confirm eligibility.
2. ER and/or PR positivity are defined as >1% of cells expressing HR via IHC
analysis as per most recent ASCO-CAP guideline. If a patient has had multiple
ER/PgR results after metastatic disease, the most recent test result prior
screening period will be used to confirm eligibility.
6. Disease refractory to CDK4/6 inhibitors, defined as recurrence during or within 12
months after the end of adjuvant treatment or progression during or within 6 months
after the end of treatment for advanced/metastatic disease.
7. No more than 1 prior systemic chemotherapy or antibody-drug conjugate (ADC) regimens
for metastatic disease. Adjuvant or neoadjuvant therapy for early-stage disease will
qualify as one of the required prior chemotherapy regimens if the development of
unresectable, locally advanced, or metastatic disease occurred within a 12-month
period of time of the therapy. Note: treatments for bone metastases (eg,
bisphosphonates, denosumab, etc.), targeted therapies (eg, PARP inhibitors, CDK 4/6
inhibitors, immunotherapy etc.) and hormonal therapy are not considered as prior
systemic chemotherapy treatments for advanced disease.
8. Radiologic or objective evidence of disease progression on or after the last
systemic therapy prior to starting study treatment
9. Measurable or non-measurable disease but evaluable (identification of target and/or
non-target lesions by RECIST Vs1.1).
10. Patients must have a site of disease amenable to safely perform a biopsy, as per
Investigator's assessment, and be a candidate for tumor biopsy according to the
treating institution's guidelines.
11. Possibility of performing a biopsy prior to the start of treatment and its
repetition after 2 weeks (14-21 days) and at End of Treatment (EOT) on the same
location. It will be provided formalin-fixed paraffin-embedded (FFPE) tumor block.
The tumor tissue should be of good quality based on total and viable tumor content
and must be evaluated centrally for quality prior to enrollment. Patients whose
tumor tissue is not evaluable for central testing are not eligible. It is
recommended to send the biopsy directly to the central lab after confirming the
existence of a tumor, so as not to delay the inclusion, without the need to carry
out IHC studies in the same sample.
- Acceptable samples include core needle biopsies for deep tumor tissue or
excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous,
bone or mucosal lesions or biopsies from bone metastases. Lymph node biopsies
are also permitted.
- Fine needle aspiration, brushing, cell pellet from pleural effusion and lavage
samples are not acceptable.
12. Patients must have normal organ and bone marrow function measured within 35 days
prior to administration of study treatment as defined below:
- Haemoglobin ≥ 9.0 g/dL *
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L*
- Platelet count ≥ 100 x 109/L*
- Total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN in the
presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia).
- AST (SGOT) / ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present in
which case, they must be ≤ 5x ULN
- Creatinine ≤ 1.5 x ULN or Creatinine clearance estimated of ≥30mL/min using the
Cockcroft-Gault equation.
- Serum albumin >3 g/dL
- International normalized ratio (INR) or prothrombin time (PT) and either
partial thromboplastin or activated partial thromboplastin time (aPTT) ≤ 1.5
×ULN *Without transfusional or growth factor support within 1 week of study
treatment initiation.
13. Patients must have a life expectancy ≥ 16 weeks.
14. Male patients and female patients of childbearing potential who engage in
heterosexual intercourse must agree to use protocol-specified method(s) of
contraception as described in Appendix 2.
15. Willing and able to comply with the requirements and restrictions in this protocol.
Exclusion Criteria:
1. Patients with HER2-positive or TNBC disease.
2. Other malignancy unless curatively treated with no evidence of disease for ≥3 years
except: non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in
situ (DCIS), Stage 1, grade 1 endometrial carcinoma or other malignant tumors with
an expected curative outcome after medical monitor approval.
3. Has unresolved toxicities from previous anticancer therapy (≥ CTCAE version 5.0
grade 1) caused by previous cancer therapy, excluding alopecia or other toxicities
not considered a safety risk for the patient at investigator's discretion. Note:
Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no
worsening to ≥Grade 2 for at least 2 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, Fatigue, Residual
toxicities from prior IO treatment Grade 1 or Grade 2 endocrinopathies. Note: if
patients received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
4. Patients may not be participating in a study with an investigational agent or
investigational device within 2 weeks or 5 half-lives, whichever is longer, prior to
allocation. Patients participating in observational studies are eligible.
5. Patients with symptomatic uncontrolled brain metastases. Participants with a history
of treated Central Nervous System (CNS) metastases are eligible, provided they meet
all of the following criteria:
- Biopsiable disease outside the CNS is present.
- No evidence of interim CNS progression between the completion of CNS directed
therapy and the screening radiographic study.
- Metastases are limited solely to cerebellar and supratentorial lesions.
- Stable requirement for corticosteroids (≤ 20 mg oral prednisone or equivalent)
or anticonvulsants during >4 weeks as therapy for CNS disease.
- No stereotactic radiation within 7 days or whole-brain radiation within 14 days
prior to enrolment.
- No evidence of progression or haemorrhage after completion of CNS directed
therapy.
- Patients with spinal cord compression are excluded unless considered to have
received definitive treatment for this and evidence of clinically stable
disease for 28 days.
6. History of significant cardiovascular disease, defined as:
- New York Heart Association Class III or greater congestive heart failure or
known left ventricular ejection fraction of < 40%.
- Unstable angina or myocardial infarction within 6 months before enrolment.
- History of serious ventricular arrhythmia (ie, ventricular tachycardia or
ventricular fibrillation), high-grade atrioventricular block, or other cardiac
arrhythmias requiring antiarrhythmic medications (except for atrial
fibrillation that is well controlled with antiarrhythmic medication); history
of QT interval prolongation.
7. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
or GI perforation within 6 months of enrollment.
8. Have active serious infection requiring requiring IV antibiotics, antivirals, or
antifungals.
9. Have a known history of Human Immunodeficiency Virus (HIV).
10. Have active HBV (defined as having a positive HbsAg test) or HCV.
1. For patients with a history of HBV infection, a hepatitis B core antibody test
should be conducted at screening. If positive, hepatitis B DNA testing will be
performed and if active HBV infection is ruled out, the patient may be
eligible.
2. Patients who are HCV antibody positive with polymerase chain reaction negative
for HCV RNA may be eligible.
11. Have other concurrent medical or psychiatric conditions that, in the investigator's
opinion, may be likely to confound study interpretation or prevent completion of
study procedures and follow-up examinations.
12. Has received a live vaccine within 30 days prior to randomization.
13. Prior treatment with Sacituzumab-govitecan.
14. Known or severe (≥ Grade 3) hypersensitivity or allergy to sacituzumab govitecan,
their metabolites, or formulation excipient.
15. Requirement for ongoing therapy with or prior use of any prohibited medications
listed in Section 7.5.
16. Positive serum pregnancy test or women who are lactating (see Appendix 2).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
ICO Badalona
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Angelica Ferrando, MD
Facility:
Name:
ICO Hospitalet
Address:
City:
L'Hospitalet De Llobregat
Zip:
08907
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Rafael Villanueva, MD
Facility:
Name:
Hospital Universitari Vall d'Hebrón
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Mafalda Oliveira, MD
Facility:
Name:
Hospital Clínic de Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Tomás Pascoal, MD
Facility:
Name:
HU Clínico San Cecilio
Address:
City:
Granada
Zip:
18016
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Isabel Blancas, MD
Facility:
Name:
Fundación Jiménez Díaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Yann Izarzugaza, MD
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Eva Ciruelos, MD
Facility:
Name:
Hospital Sant Joan de Reus
Address:
City:
Reus
Zip:
43204
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Kepa Amillano, MD
Facility:
Name:
Hospital Universitario Virgen del Rocio
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Javier Salvador Bofil, MD
Facility:
Name:
Hospital Clínico de Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Juan M Cejalvo, MD
Start date:
March 15, 2024
Completion date:
February 20, 2027
Lead sponsor:
Agency:
SOLTI Breast Cancer Research Group
Agency class:
Other
Source:
SOLTI 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/NCT06236269
