Vepdegestrant + Samuraciclib for Advanced Breast Cancer
Recruiting in Palo Alto (17 mi)
+46 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Pfizer
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat.
The study is seeking for participants who have breast cancer that:
* is hard to treat (advanced) and may have spread to other organs (metastatic). is sensitive to hormonal therapy (it is called estrogen receptor positive).
* is no longer responding to treatments taken before starting this study.
This study is divided into separate sub-studies.
For Sub-Study C:
All the participants will receive vepdegestrant and a medicine called samuraciclib.
Vepdegestrant and samuraciclib will be taken once in a day by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicine is safe and effective.
Participant will continue to take vepdegestrant and samuraciclib until:
* their cancer is no longer responding, or
* side effects become too severe.
They will have visits at the study clinic about every 4 weeks.
Do I need to stop my current medications for this trial?
The trial protocol does not specify if you must stop all current medications, but you cannot take medications, foods, or supplements that strongly affect certain liver enzymes (CYP3A, CYP2D6) or those that can cause heart rhythm issues.
What data supports the idea that Vepdegestrant + Samuraciclib for Advanced Breast Cancer is an effective drug?
The available research does not provide specific data on the effectiveness of Vepdegestrant + Samuraciclib for Advanced Breast Cancer. Instead, it discusses other treatments like palbociclib combined with fulvestrant, which improved outcomes in certain breast cancer patients. Without direct data on Vepdegestrant + Samuraciclib, we cannot compare its effectiveness to these other treatments.
12345What safety data is available for Vepdegestrant and Samuraciclib in advanced breast cancer treatment?
The provided research does not contain specific safety data for Vepdegestrant (ARV-471, PF-07850327) and Samuraciclib in the treatment of advanced breast cancer. The studies listed focus on different chemotherapy regimens and treatments for breast and prostate cancer, but do not mention Vepdegestrant or Samuraciclib. Further research or clinical trial data specific to these drugs would be needed to answer the question.
678910Is the drug Samuraciclib, Vepdegestrant a promising treatment for advanced breast cancer?
Yes, Samuraciclib, Vepdegestrant is a promising treatment for advanced breast cancer because it is being studied in combination with other drugs to improve outcomes for patients with this type of cancer. It aims to target specific pathways in cancer cells, potentially leading to better control of the disease.
1251112Eligibility Criteria
This trial is for individuals with advanced or metastatic breast cancer that's hormone-sensitive and not responding to prior treatments. Participants can have had up to two previous therapies for advanced disease, including one CDK4/6 inhibitor regimen, and must have at least one measurable lesion. They should be in a relatively stable condition (ECOG PS ≤1) without life-threatening visceral crises, significant lung function issues, recent other cancers except certain skin/cervix ones, inflammatory breast cancer, serious heart diseases or conditions affecting the kidneys, liver or bone marrow.Inclusion Criteria
You have at least one specific type of visible abnormality that can be measured according to certain guidelines.
I am fully active and can carry on all pre-disease activities without restriction.
My breast cancer cannot be removed with surgery to cure it.
+1 more
Exclusion Criteria
I have had lung problems caused by medication before.
I haven't had any cancer except for certain skin cancers or treated cervical cancer in the last 3 years.
I currently have an active infection.
+6 more
Participant Groups
The study tests vepdegestrant combined with samuraciclib taken orally once daily at home by patients with tough-to-treat breast cancer. The goal is to determine the safety and effectiveness of this combination therapy in controlling cancer that has spread beyond the breast.
1Treatment groups
Experimental Treatment
Group I: ARV-471 in combination with SamuraciclibExperimental Treatment2 Interventions
ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Siteman Cancer Center - West CountyCreve Coeur, MO
Siteman Cancer Center - ShilohShiloh, IL
Clinical and Translational Research Unit (CTRU)Palo Alto, CA
Stanford Cancer CenterPalo Alto, CA
More Trial Locations
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Who Is Running the Clinical Trial?
PfizerLead Sponsor
Arvinas Estrogen Receptor, Inc.Industry Sponsor
Carrick Therapeutics LimitedIndustry Sponsor
References
Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. [2023]In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer (ABC).
AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer. [2022]Label="Background" NlmCategory="UNASSIGNED">For estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), the current standard first-line treatment includes an aromatase inhibitor in combination with a cyclin-dependent kinase 4/6 inhibitor. When resistance occurs, often related to the occurrence of ESR1 mutations, selective estrogen receptor modulators or degraders (SERDs) may be used, alone or in combination regimens. Amcenestrant (SAR439859), an optimized oral SERD, has shown clinical antitumor activity in combination with palbociclib in patients with ER+/HER2- ABC and, as monotherapy, in patients with and without ESR1 mutations. Here, we describe the study design of AMEERA-5, an ongoing, prospective, phase 3, randomized, double-blind, multinational study comparing the efficacy and safety of amcenestrant plus palbociclib versus letrozole plus palbociclib in patients with advanced (locoregional recurrent or metastatic) ER+/HER2- breast cancer.
Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. [2022]The LORDSHIPS study aimed to explore the safety and efficacy of a novel fully oral triplet combination of dalpiciclib (a potent cyclin-dependent kinase 4/6 inhibitor), pyrotinib (a HER2 tyrosine kinase inhibitor) and endocrine therapy letrozole in patients with HER2-positive, hormone receptor (HR)-positive metastatic breast cancer (MBC) in the front-line setting.
Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]The combination of fulvestrant with alpelisib, a PI3K inhibitor, improves progression-free survival in metastatic hormone receptor-positive, PIK3CA-mutant breast cancer. This study describes the incidence, risk factors, and treatment of alpelisib-associated hyperglycemia.
Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. [2018]Purpose: Estrogen receptor-positive (ER+) breast cancers are typically treated with endocrine agents, and dependence on the ER pathway is often retained even after multiple rounds of antiestrogen therapy. Selective estrogen receptor degraders (SERD) are being developed as a strategy to more effectively target ER and exploit ER dependence in these cancers, which includes inhibiting both wild-type and mutant forms of ER. The purpose of this study was to evaluate the efficacy of a novel orally bioavailable SERD, elacestrant (RAD1901), in preclinical models of ER+ breast cancer.Experimental Design: Elacestrant was evaluated as a single agent and in combination with palbociclib or everolimus in multiple ER+ breast cancer models, including several patient-derived xenograft models.Results: Elacestrant induces the degradation of ER, inhibits ER-mediated signaling and growth of ER+ breast cancer cell lines in vitro and in vivo, and significantly inhibits tumor growth of multiple PDX models. Furthermore, we demonstrate that elacestrant in combination with palbociclib or everolimus can lead to greater efficacy in certain contexts. Finally, elacestrant exhibits significant antitumor activity both as a single agent and in combination with palbociclib in two patient-derived breast cancer xenograft models harboring ESR1 mutations.Conclusions: These data underscore the potential clinical utility of elacestrant as a single agent and as a combination therapy, for both early- and late-stage ER+ disease. Clin Cancer Res; 23(16); 4793-804. ©2017 AACR.
Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care. [2017]To assess the clinical toxicity and outcome associated with a comprehensive supportive care approach in poor-risk breast cancer (BrCA) patients with high-dose chemotherapy (HDC).
Vinorelbine and fluorouracil plus leucovorin combination (ViFL) in patients with anthracycline and taxane-pretreated metastatic breast cancer: a phase II study. [2021]This phase II study was designed in order to evaluate efficacy and safety of the combination of vinorelbine (VNB), fluorouracil (FU) and leucovorin (LV) in patients with metastatic breast carcinoma (MBC) previously treated with anthracyclines and taxanes.
Combination chemotherapy with docetaxel, vinorelbine and estramustine phosphate in metastatic androgen-resistant prostate cancer: a single institution experience. [2018]The aim of this study was to evaluate the activity and toxicity of docetaxel, vinorelbine and oral estramustine in androgen-resistant prostate cancer (ARPC).
Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. [2020]Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients.
Vinorelbine and estramustine in androgen-independent metastatic prostate cancer: a phase II study. [2019]The aim of this study was to determine the safety and activity of vinorelbine in combination with estramustine in men with androgen-independent metastatic prostate cancer.
Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that is licensed in the USA, Brazil, Europe and elsewhere for the treatment of advanced breast cancer (ABC) in postmenopausal women following progression on other endocrine agents. This report consolidates clinical experience from the "Faslodex" Compassionate Use Programme, including a total of 339 patients treated at eight cancer centres. Patients received fulvestrant as first- (n=22), second- (n=125), third- (n=105), fourth- (n=58), fifth- (n=22) or sixth-line (n=5) hormonal treatment for ABC, with two patients receiving fulvestrant after more than six other endocrine therapies. Objective response was achieved by 40 patients and stable disease lasting 6 months by 92 patients, giving overall clinical benefit (CB) in 132/339 patients (39%). The CB rate decreased as fulvestrant was used later in the sequence of endocrine treatments, from 46% (10/22) with first-line fulvestrant to 27% (6/22) with fifth-line fulvestrant. Increased benefit was found in patients with tumours expressing both ER and progesterone receptor (PgR) compared with other combinations, although good activity was reported in patients expressing either ER or PgR as well as in tumours expressing human epidermal growth factor receptor 2. Fulvestrant was well tolerated; adverse events were noted in 18/339 patients (5%). These findings concur with data from the clinical-trial setting and further support the assertion that greater benefit is derived when fulvestrant is used early in the treatment sequence.
An evaluation of fulvestrant for the treatment of metastatic breast cancer. [2019]Introduction: Fulvestrant is currently the only selective estrogen receptor degrader (SERD) that is approved for clinical use in estrogen receptor (ER) positive advanced breast cancer (ABC). The drug is approved as single-agent therapy in the first and second-line setting of metastatic ER-positive breast cancer. Areas covered: In this review, the authors review the preclinical studies that were pivotal in the development of fulvestrant, the pharmacologic properties of the drug, and the key clinical trials that resulted in its approval for clinical use. The authors discuss mechanisms of endocrine resistance and potential targets for endocrine refractory disease while highlighting ongoing studies that assess fulvestrant use with novel agents. Expert opinion: While fulvestrant has limited use in the first-line setting in advanced breast cancer, it is most frequently used in the second line after progression with aromatase inhibitors. The combination of fulvestrant with CDK4/6 inhibitors has shown a clear benefit over monotherapy in patients who progress on prior endocrine therapy. Further study is necessary to assess if patient outcomes can be enhanced by optimizing the sequence of endocrine therapies, targeting resistance pathways with novel agents, and development of new agents in the SERD class.