Clinical Research Directory

A Study of JNJ-101684362 (HLD-0117) in Patients With Metastatic Breast Cancer

The purpose of this study is to find out the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of JNJ-101684362 (HLD-0117), to evaluate the safety of JNJ-101684362 (HLD-0117) , and how well the participants can tolerate it in Part 1 (dose escalation) of the study.

The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study

The purpose of this study is to generate evidence on an alternative dosing strategy for CDK4/6 inhibitors to help more patients with Metastatic Breast Cancer (MBC) (age ≥ 60 years) tolerate side effects and stay on treatment longer, to derive the most clinical benefit from these drugs. The primary objective of the CDK Study is to compare time to treatment discontinuation (TTD) on the approved dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day cycle) or ribociclib (600 mg orally daily on days 1-21 of 28-day cycle) vs. TTD using titrated dosing approach with the same schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) or ribociclib (400 mg or 200 mg) and escalating the dose if well-tolerated in combination with provider/patient choice endocrine therapy (aromatase inhibitor (AI) or fulvestrant) in patients age 60 or older with HR+/HER2- MBC. The secondary and exploratory objectives will generate evidence needed to personalize treatment decisions by comparing patient-centric secondary outcomes and evaluating baseline factors. Together with their treating physician, participants will choose the CDK4/6 inhibitor (palbociclib or ribociclib) and which endocrine therapy (aromatase inhibitor or fulvestrant) of their choice but will be randomized to either Arm 1 (indicated dosing) or Arm 2 (titrated dosing). Note: Telehealth visits are allowed at any time per institutional guidelines. In addition, the study allows for remote consenting per institutional guidelines.

Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer

The purpose of this study is to evaluate the use of lovastatin, a cholesterol-depleting pro-drug that may lower CAV-1 levels, in order to increase HER2 expression on the cell surface of cancer cells and enhance the uptake and efficacy of trastuzumab deruxtecan (T-DXd) in HER2-low and ultralow breast tumors.

Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of ESR1 Mutations in HR+/HER2- Metastatic Breast Cancer (MBC)

This is a prospective, single center, single-arm interventional study to evaluate the clinical utility of protocol-mandated diagnostic testing algorithm incorporating liquid biopsy and reflex tissue biopsy NGS for detection of ESR1 mutations in HR+/HER- metastatic breast cancer.

Targeting Aurora A Kinase to Overcome Treatment Resistance in Advanced HR+/HER2+ Breast Cancer

The goal of this clinical trial is to learn if alisertib in addition to usual care works to treat HR+/HER2+ breast cancer. The main questions it aims to answer are: * Does alisertib stop the communication between HR and HER2? * Are there genetic markers that predict how well someone's cancer will respond to alisertib? Participants will receive alisertib in addition to their usual care.

Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation. The main question the study aims to answer is: • To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.

A Phase 1/1b Study of PRT13722 in Participants With Advanced HR+/HER2- Breast Cancer

This first-in-human, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722, an oral KAT6A protein degrader, in adults with locally advanced or metastatic Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. PRT13722 will be evaluated as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion (RDE) and evaluate preliminary clinical activity.

Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread

This study is open to adults aged 18 years and older with different types of HER2+ cancer that has spread and cannot be removed by surgery. People can take part in this study if their tumours show HER2 aberrations and previous treatment was not successful. The purpose of this study is to find a suitable dose of zongertinib that people with different types of HER2+ cancer that has spread can tolerate best when taken together with trastuzumab deruxtecan (T-DXd), with trastuzumab emtansine (T-DM1), with trastuzumab and capecitabine, with zanidatamab, or with mFOLFOX6 (with or without trastuzumab). Another purpose is to check whether zongertinib alone and in combination with other treatments can make tumours shrink. Zongertinib inhibits HER2. HER2 causes cancer cells to grow. In this study, participants receive treatment in cycles. Study participants are treated with zongertinib alone or in combination with other treatments. This study has 2 parts. In Part 1, participants in different groups receive increasing doses of zongertinib. In Part 2, participants are put into different groups by chance. Each group receives a different dose of zongertinib. Every participant has an equal chance of being in each group. During the study, the participants visit the study site regularly. In this study, researchers want to find the highest dose of zongertinib that participants can tolerate when taken together with other treatments. To find this out, researchers look at certain severe health problems that a number of participants have. The doctors regularly check the size of the tumour with imaging methods (CT/MRI) during the study. The doctors also regularly check participants' health and take note of any unwanted effects.

HER2 Targeted Molecular Imaging in mBC and Other Metastatic Solid Carcinomas Using 68Ga-ABS011

This phase II study aims to confirm the diagnostic performance and accuracy of 68Ga-ABS011 PET/CT in determining the HER2 expression status, and to evaluate 68Ga-ABS011's ability to drive changes in therapeutic treatment. 68Ga-ABS011 will be compared to the current standard of care (SOCa) diagnostic methods including immunohistochemistry (IHC), in situ hybridization (ISH) and imaging tools used for treatment response follow-up including Fluorodeoxyglucose F-18 (18F-FDG) positron emitted tomography (PET) and contrast enhanced computed tomography (ceCT).

Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis

This study is a prospective evaluation of systemic, intravenous high-dose methotrexate (HD-MTX, 8 g/m2) in patients with triple negative, HER2-positive, and hormone refractory breast cancer with leptomeningeal metastasis (LMD) with or without brain parenchymal involvement.

Mapping the Enhanced Landscape of Advanced Breast Cancer fOr DYnamic Treatment Approaches

MELODY is a prospective, single-arm phase II study introducing routine liquid-biopsy next-generation sequencing for patients with advanced or unresectable breast cancer in Ireland. The study will characterise genomic alterations detected in plasma and tumour tissue, assess concordance and clinical actionability, and evaluate clinical, operational, economic, patient-reported and exploratory translational outcomes.

Organ Culture for Endocrine Resistant Next Line: A Treatment Selection Study in Metastatic Breast Cancer

This study evaluates whether testing fresh tumor samples outside the body can help guide treatment selection for patients with hormone receptor-positive, HER2-negative metastatic breast cancer that has progressed during endocrine therapy. A biopsy sample from each participant will be tested using an ex vivo organ culture (EVOC) platform, which preserves the tumor tissue and allows researchers to assess its response to different anticancer treatments. The results will be used to help select the participant's next systemic treatment. The main objective is to evaluate the proportion of patients whose cancer responds to treatment selected using this approach. The study will also assess how long the cancer remains controlled, overall survival, and the relationship between laboratory test results and clinical outcomes.

Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks

The aim of the trial is to test the hypothesis that the benefit of denosumab is maintained if administered only every 12 weeks as compared to every 4 weeks.

Roll-over Study to Allow Continued Access to Ribociclib

The purpose of this study is to assess the long-term safety of ribociclib (LEE011) in combination with other drugs and provide post-trial access (PTA) to participants who are currently receiving treatment with ribociclib in combination with other drugs and continuing to have clinical benefit in a Novartis-sponsored global study that has reached its primary objective(s).

T-DXd Based Therapy Followed by Endocrine Therapy Plus Dual HER2 Blockade in First-line HER2+/ HR+ Metastatic Breast Cancer and Retreatment With T-DXd

This study will evaluate a structured sequential treatment strategy starting with T-DXd + pertuzumab upfront therapy, followed by an optimized maintenance therapy with dual HER2+blockade + CDK4/6i + ET and the opportunity to retreat with T-DXd once patients progress under maintenance aimed to maximizing disease control, optimizing tolerability, and preserving T-DXd as a future therapeutic option, while ensuring participant safety and regulatory compliance in participants with HER2+/HR+ advanced/metastatic breast cancer.

A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer

This study will evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for subcutaneous use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC).

A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer

The main purpose of this study is to evaluate the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic breast cancer.

Detection of Germline and Somatic Pathogenic Variants in Patients With de Novo Metastatic Breast Cancer

To determine somatic and germline pathogenic variants in patients with denovo metastatic breast cancer in order to map the molecular/genetic characteristics of DN- MBC aiming in comprehending the biology and highlighting potential novel treatment options for the disease.

Minimally Interventional Study on Prevalence of Emerging ESR1 Mutations in Liquid Biopsy in Three Cohorts of Patients With Breast Cancer in Comparison With Patient's Baseline ESR1 Mutation Status as Defined by Tissue Profiling.

Minimally interventional study on prevalence of emerging ESR1 mutations in liquid biopsy in three cohorts of patients with breast cancer (with and without prior therapies in metastatic setting, and during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy) in comparison with patient's baseline ESR1 mutation status as defined by tissue profiling.

Prospective Registry of ADC as First- and Second-line Treatment for Breast Cancer

Antibody-drug conjugates (ADCs) have demonstrated substantial improvement in progression free survival (PFS) and overall survival (OS) in phase III clinical trials in patients with metastatic triple negative breast cancer (mTNBC) and hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC), offering an effective new treatment strategy. Several outstanding questions drive the decision to use ADC drugs clinically. This is a prospective, multi-site observational study of patients with metastatic breast cancer (mBC) who are being treated with FDA-approved antibody drug conjugates (ADCs) as part of routine care and aims to collect real-world data to evaluate the impact of ADC treatment as part of routine care.

SMP-656 for HER2-Positive Advanced Breast Cancer

The goal of this clinical trial is to learn if single-agent SMP-656 works to treat patients with HER2-positive locally advanced or metastatic breast cancer who have progressed after prior HER2-targeted topoisomerase inhibitor antibody-drug conjugate (ADC) treatment. It will also evaluate the safety of SMP-656 and identify the optimal dose for future trials. The main questions it aims to answer are: What is the objective tumor response rate (DOR, PFS, DCR, OS) of two different dose regimens of intravenous SMP-656? What are the side effects and safety risks of these two SMP-656 dose regimens? Which dose level achieves the best balance of anti-cancer activity and tolerability? This is a randomized, open-label, dose-optimization Phase II clinical trial. Participants will be randomly assigned 1:1 to receive one of two fixed doses of SMP-656 given intravenously once every 3 weeks. Participants will: Complete screening tests within 28 days before the first SMP-656 infusion to confirm eligibility Receive study treatment every 3 weeks until cancer progression, intolerable side effects, withdrawal, or other stopping criteria Have regular tumor imaging scans, physical exams, vital sign checks, and blood tests to monitor tumor response and safety Attend a safety follow-up visit 30 days after the last dose of SMP-656 Complete longer-term survival follow-up after the 30-day safety check Provide optional blood and tumor tissue samples for additional research studies

Sexual Health and Rehabilitation for Women With Metastatic Breast Cancer (SHARE-MC): An Educational Intervention

This trial will evaluate the SHARE-MC educational intervention designed to address sexual health needs and related adjustment in women with metastatic breast cancer.

A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer

This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).

Anastrazole, Fulvestrant & Abemaciclib for HR+HER2- Metastatic Breast Cancer

This is a phase 2, open-label, singled-arm clinical trial determining efficacy of combination therapy with anastrozole, fulvestrant and abemaciclib in subjects with breast cancer. These are subjects who are newly diagnosed advanced or metastatic hormone receptor positive breast cancer or subjects who have progressed following treatment free interval of more than 12 months following adjuvant or neoadjuvant treatment.