Phase II Study on Sacituzumab Govitecan, Loperamide, and Filgrastim in Metastatic Triple-Negative and Luminal Breast Cancer Patients
- Trial ID
- 2024-514060-10-00
- Protocol
- MEDOPP445
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the incidence of **diarrhea** and **neutropenia** in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) or luminal breast cancer treated with sacituzumab govitecan in combination with loperamide and G-CSF. This is clinically relevant as it aims to improve the management of adverse effects associated with sacituzumab govitecan, potentially enhancing patient outcomes and treatment adherence.
Secondary objectives include:
- To determine the safety and tolerability of the study regimen in this patient population.
- To determine the efficacy of the study regimen in this patient population.
- Exploratory objectives: To evaluate predictive or prognostic biomarkers associated with disease activity status or response to treatment.
- Exploratory objectives: To identify possible mechanisms of sensitivity/resistance to study treatment through the comparative analysis of potential biomarkers from paired pre-treatment and post-progression blood samples and/or stool samples.
Participants
The clinical trial involves participants diagnosed with **advanced triple-negative breast cancer (TNBC)** or advanced HR[+]/HER2[–] breast cancer. The study population includes both male and female subjects aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have a life expectancy of at least 12 weeks and must have completed all prior cancer treatments, including chemotherapy, radiotherapy, and major surgery, at least two weeks before randomization. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to have adequate hematologic, renal, and hepatic function and must have been previously treated with taxanes. The trial population was selected based on specific inclusion criteria, such as having unresectable locally advanced or metastatic disease documented by CT or MRI, and being refractory to at least one prior standard of care chemotherapy regimen. Lifestyle considerations, such as diet and physical activity, are not specified in the trial data provided.
Plans and Procedures
The clinical trial is designed as a **single-arm**, open-label, Phase II study aimed at evaluating the tolerance of **sacituzumab govitecan** in patients with metastatic triple-negative or luminal breast cancer. The primary objective is to assess the incidence of diarrhea and neutropenia in patients treated with sacituzumab govitecan in combination with **loperamide hydrochloride** and **filgrastim**. The trial is expected to commence on February 1, 2023, and conclude by January 30, 2026, with an estimated duration of three years.
Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed through criteria such as age, performance status, and prior treatment history. The inclusion visit will involve obtaining informed consent and conducting baseline assessments, including imaging and laboratory tests. Follow-up visits will occur at regular intervals to monitor treatment response and adverse events, with specific attention to the incidence of grade ≥2 diarrhea and grade ≥3 neutropenia, as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v.5.0). The end-of-study visit will involve a comprehensive evaluation of the participant's health status and the collection of final data points.
The expected length of participant involvement is approximately 30 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, disease progression, or withdrawal of consent by the participant. The trial will also explore secondary endpoints such as the incidence of febrile neutropenia, objective response rate, and progression-free survival, alongside exploratory endpoints related to tumor biomarkers and gut microbiome changes.
Treatment
The clinical trial involves the administration of **sacituzumab govitecan**, marketed as Trodelvy, which is provided as a 200 mg powder for concentrate for solution for infusion. This medication is administered via infusion, with a maximum daily dose of 200 mg. The treatment period is set for a maximum of 30 days. Sacituzumab govitecan is a protein-based therapeutic agent, and its administration is intended to evaluate its tolerance in patients with metastatic triple-negative or luminal breast cancer.
In addition to sacituzumab govitecan, the trial includes the use of **loperamide hydrochloride**, provided in the form of 2 mg tablets. Loperamide hydrochloride is administered orally, with a maximum daily dose of 2 mg, also over a treatment period of up to 30 days. This chemical-based medication is used as an antidiarrheal agent to manage potential side effects associated with the primary treatment.
The trial also incorporates the use of **filgrastim**, which is available under several brand names, including Neupogen Singleject, Accofil, and Zarzio. These are provided as solutions for injection or infusion in pre-filled syringes, with varying concentrations and dosages. Neupogen Singleject is available in two formulations: 30 MU (0.6 mg/ml) and 48 MU (0.96 mg/ml), while Accofil and Zarzio are available as 30 MU/0.5 ml and 48 MU/0.5 ml solutions, respectively. Filgrastim is administered via injection or infusion, with a maximum daily dose of 30 to 48 MU, depending on the formulation, over a 30-day treatment period. Filgrastim is a protein-based agent used to manage neutropenia, a potential side effect of the primary treatment.
Efficacy
The efficacy of the clinical trial will be assessed through a series of predefined endpoints. The primary endpoints include the incidence of grade ≥2 diarrhea and grade ≥3 **neutropenia** as assessed by the Investigator, with severity determined by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v.5.0) at cycle 2. Secondary endpoints will evaluate the incidence of all grades and grade ≥3 diarrhea and neutropenia, incidence of febrile neutropenia, and additional adverse events as per NCI-CTCAE v.5.0. Other secondary measures include discontinuation rate, dose reduction rate, objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), time to response (TtR), best percentage of change from baseline in the size of target tumor lesions, and progression-free survival (PFS).
Exploratory endpoints will investigate the relationship between tumor-related biomarkers and treatment efficacy, including mutational tumor load and cytokine profiling. Additionally, changes in mutation and copy number in oncogenes, tumor suppressors, and other genes associated with disease progression will be assessed in liquid biopsy and/or tumor tissue. Changes in gut microbiome and metabolomic profile in stool samples will also be explored. These efficacy parameters will be measured and analyzed at specified timepoints throughout the trial to ensure comprehensive evaluation of the treatment's impact on the patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed Informed Consent Form (ICF) prior to participation in any study-related activities.
- Patients aged ≥18 years at the time of signing ICF.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of ≥ 12 weeks
- Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
- All patients must have been previously treated with taxanes regardless of disease stage (adjuvant, neoadjuvant, or advanced), unless contraindicated for a given patient.
- Refractory to at least one, and no more than two, prior standard of care chemotherapy regimens for unresectable locally advanced or MBC. Earlier adjuvant or neoadjuvant therapy for more limited disease will be considered as one of the required prior regimens if the development of unresectable locally advanced or metastatic disease occurred within a 12-month period after completion of chemotherapy or immunotherapy (e.g., adjuvant pembrolizumab).
- For TNBC patient only: Histologically confirmed TNBC per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as <1% expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for human epidermal growth factor receptor 2 (HER2) (0–1+ by IHC or 2+ and negative by in situ hybridization [ISH) test].
- For HR positive luminal breast cancer patients only: a.) Confirmed diagnosis of estrogen receptor (ER)[+] and/or progesterone receptor (PR)[+] (with ≥1% positive stained cells according to National Comprehensive Cancer Network [NCCN] and American Society of Clinical Oncology [ASCO] guidelines) and human epidermal growth factor receptor 2 (HER2)- negative (0 or 1+ by immunohistochemistry [IHC] or 2+ and negative by in situ hybridization [ISH] test) breast cancer in the advanced setting.
- For HR positive luminal breast cancer patients only: b.) Refractory to at least 1 prior anticancer hormonal treatment and at least 1 CDKi4/6 in the metastatic setting.
- Measurable or non-measurable, but evaluable disease, as per RECIST v.1.1. Patients with bone-only metastases are also eligible.
- Brain MRI must be done for patients with suspicion of brain metastases and patient must have stable central nervous system (CNS) disease for at least 4 weeks after local therapy, without neurological symptoms, and off anticonvulsants and steroids for at least 2 weeks before first dose of study treatment.
- Adequate hematologic counts without transfusion or growth factor support within 2 weeks before of study drug initiation (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3 , and platelets ≥ 100,000/μL).
- Adequate renal and hepatic function (creatinine clearance of ≥ 60 ml/min, may be calculated using Cockcroft-Gault equation; bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3.0 x ULN or 5 x ULN if known liver metastases)
- Resolution of all acute AEs of prior anti-cancer therapy to grade 1 as determined by the NCI-CTCAE v.5.0 (except for alopecia or other toxicities not considered a safety risk for the patient at investigator discretion).
- Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use institution specified method(s) of contraception.
- Patients must have completed all prior cancer treatments at least 2 weeks* prior to randomization including chemotherapy (includes also endocrine treatment), radiotherapy, and major surgery.
- *Prior antibody treatment for cancer must have been completed at least 3 weeks prior to randomization.
Exclusion Criteria
- Prior treatment with topoisomerase 1 inhibitors as a free form or as other formulations.
- Patients with carcinomatous meningitis or leptomeningeal disease.
- Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
- Patients with Gilbert's disease.
- Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
- Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while participants with other prior malignancies must have had at least a 3-year disease-free interval.
- Known history of unstable angina, myocardial infarction, or cardiac heart failure present within 6 months of study initiation or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy or history of QT interval prolongation.
- Known history of clinically significant active Chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months of study initiation
- Known history of clinically significant bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study initiation.
- Active or prior documented inflammatory bowel disease (i.e. Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline grade ≥1 diarrhea).
- Infection requiring antibiotic use within 1 week of randomization.
- 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.
- Women who are pregnant or lactating.
- Concomitant participation in other interventional clinical trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Feb 2023 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Accofil 30 MU/0.5 ml solution for injection or infusion in pre-filled syringe | Other | SOLUTION FOR INJECTION OR INFUSION IN PRE-FILLED SYRINGE | SOLUTION FOR INJECTION OR INFUSION | 30 | 30 | PRD1688283 |
Neupogen Singleject 48 MU (0.96 mg/ml) solution for injection in a pre-filled syringe filgrastim | Other | SOLUTION FOR INJECTION IN A PRE-FILLED SYRINGE | SOLUTION FOR INJECTION OR INFUSION | 48 | 30 | PRD376887 |
Neupogen Singleject 30 MU (0.6 mg/ml) solution for injection in a pre-filled syringe filgrastim | Other | SOLUTION FOR INJECTION IN A PRE-FILLED SYRINGE | SOLUTION FOR INJECTION OR INFUSION | 30 | 30 | PRD389467 |
Zarzio 48 MU/0.5 ml solution for injection or infusion in pre-filled syringe | Other | SOLUTION FOR INJECTION OR INFUSION IN PRE-FILLED SYRINGE | SOLUTION FOR INJECTION OR INFUSION | 48 | 30 | PRD6059198 |
Loperamide Hydrochloride 2mg Tablets | Other | TABLETS | ORAL | 2 | 30 | PRD10022251 |
Trodelvy 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INFUSION | 200 | 30 | PRD9351384 |