RGT-419B + Hormonal Therapy for Breast Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Regor Pharmaceuticals Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new oral drug, RGT-419B, for patients with advanced breast cancer who haven't responded to other treatments. The study aims to see if the drug can safely stop cancer cell growth.
Is RGT-419B + Hormonal Therapy a promising treatment for breast cancer?Yes, RGT-419B combined with hormonal therapy is promising because it targets specific pathways that help breast cancer grow, potentially improving the effectiveness of hormone therapy and increasing survival rates.123712
What safety data exists for RGT-419B + Hormonal Therapy for Breast Cancer?The safety data for treatments similar to RGT-419B, such as CDK4/6 inhibitors combined with hormonal therapy, indicate that while these targeted therapies improve outcomes, they can have complex and potentially severe adverse events. Management of these toxicities requires a multidisciplinary approach. Common toxicities include neutropenia for CDK4/6 inhibitors like palbociclib, which is managed with dose reduction or delay. The safety profile of these therapies is more complex compared to traditional endocrine therapies.79101113
What data supports the idea that RGT-419B + Hormonal Therapy for Breast Cancer (also known as: RGT-419B) is an effective treatment?The available research shows that combining hormonal therapy with other agents, like mTOR inhibitors, has improved treatment outcomes for breast cancer. While specific data on RGT-419B is not provided, similar combinations have shown to delay resistance and improve survival rates. For example, adding ribociclib, a similar type of drug, to hormonal therapy has significantly improved the time patients live without the cancer getting worse and overall survival. This suggests that RGT-419B, when combined with hormonal therapy, could also be effective.456812
Do I need to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14-28 days before starting the trial. It's best to discuss your current medications with the trial team.
Eligibility Criteria
This trial is for adults with HR+, HER2- advanced or metastatic breast cancer who've had no more than one prior chemotherapy in this setting and less than three lines of CDK4/6i therapy. Participants must have an ECOG Performance Status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory.Inclusion Criteria
My tumor is HR positive, HER2 negative, and can be measured.
I am fully active or can carry out light work.
Exclusion Criteria
My cancer has spread to my organs, causing severe problems.
I haven't had major surgery or cancer treatment in the last 14 days.
I have not had radiation to more than a quarter of my bone marrow and my organs are functioning well.
Treatment Details
The study tests RGT-419B, a new oral medication, alone or combined with hormonal therapy. It's a phase I trial focusing on safety, how the body processes the drug (pharmacokinetics), and its initial effectiveness against certain types of breast cancer that progressed after previous treatments.
2Treatment groups
Experimental Treatment
Group I: Arm BExperimental Treatment1 Intervention
RGT-419B in combination with Hormonal Therapy
Group II: Arm AExperimental Treatment1 Intervention
RGT-419B given alone as monotherapy
Find a clinic near you
Research locations nearbySelect from list below to view details:
Hem-Onc Associates of the Treasure CoastPort Saint Lucie, FL
Emory UniversityAtlanta, GA
Massachusetts General HospitalBoston, MA
New York Cancer and Blood SpecialistsPort Jefferson Station, NY
More Trial Locations
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Who is running the clinical trial?
Regor Pharmaceuticals Inc.Lead Sponsor
References
Treatment of advanced breast cancer with aminoglutethimide--response after previous tamoxifen treatment. [2014]Thirty-one postmenopausal patients with advanced breast cancer either unresponsive to tamoxifen or progressing after responding to tamoxifen were treated with aminoglutethimide (1 000 - 1 250 mg/d) plus hydrocortisone replacement. The response rate was 33% in patients who had never responded to tamoxifen and 47% in patients who had previously responded to tamoxifen. The overall response rate was 42%. These results show that aminoglutethimide is an effective second-line hormonal treatment for patients with advanced breast cancer.
Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer. [2019]Eighty-one postmenopausal women with advanced breast cancer were studied for the effects of treatment with aminoglutethimide (AG) plus hydrocortisone on peripheral hormones and response to therapy. There were 40 responders (R) and 41 non-responders (NR) at 3 months from the start of treatment. Plasma oestrone concentrations were higher in non-responders at 1 and 2 months after starting AG (Means: NR 106 +/- 50, R 84 +/- 26 pmol l-1, P less than 0.05; highest value NR 121 +/- 51, R 99 +/- 24 pmol l-1, P less than 0.05). High oestrone levels were correlated with bulky liver secondaries, but not with age, tumour-free interval, time from last menstrual period, time from relapse to start of AG or body weight. Non-responders had higher mean prolactin levels on treatment (prolactin less than 500 mIUl-1 in 14/40 NR, 2/35 R, P less than 0.01). High oestrone or prolactin levels were present in 28/41 NR and 6/40 R (P less than 0.001). Dehydroepiandrosterone sulphate suppression did not differ between R and NR. The differences in peripheral endocrine environment in non-responding patients suggest that oestrogen metabolism may differ in non-responding patients and that sub-groups could be selected for rational endocrine therapy.
[Hormone therapy of breast cancer in the metastatic phase in menopausal women]. [2016]Hormone therapy for breast cancer was initially used before menopause due to the castration effect but rapidly was extended to menopaused women. Over the last 20 years, two major types of hormone therapy have been developed, those based on surgical removal of the adrenal or pituitary glands and medical treatment with estrogens and androgens. There are currently 3 major classes of medical hormone therapies. Antiestrogens can provide objective remission in about one-third of the patients. These drugs block the estrogen receptors. Progestins can also be effective in about 40% of the patients. The third class currently includes two aromatase inhibitors, aminoglutethimide and 4 OH androstenedione. These drugs block estrogen and estradiol secretion in the ovaries and adrenal glands. Combination therapies have also been used in an attempt to take advantage of the different mechanisms of action. Others have added chemotherapy, attempting to optimize the chronology of these two complementary treatments. In case of relapse after an initial treatment, second line hormonotherapy can again be used, with objective response varying from 32 to 46% in patients who had responded to the initial treatment.
Update on endocrine therapy for breast cancer. [2006]The choice of endocrine agent for breast cancer depends on the menopausal status of the patient, the stage of disease, prognostic factors, and the toxicity profile of the agent. Endocrine therapies are typically given sequentially, with the least toxic therapy given first. Tamoxifen is considered first-line endocrine therapy for all stages of breast cancer. New antiestrogens in development include nonsteroidal agents related to tamoxifen and pure steroidal antiestrogens. Luteinizing hormone-releasing hormone agonists are an effective form of endocrine therapy for premenopausal women with advanced breast cancer, and aromatase inhibitors are effective in postmenopausal women. Newer and more selective aromatase inhibitors that are p.o. active and have improved side-effect profiles have been developed. Recent trials have found these agents to improve survival in comparison to the progestins; thus, aromatase inhibitors are replacing progestins as second-line therapy for metastatic disease. Current trials are examining the potential role of aromatase inhibitors as first-line therapy for metastatic disease or as adjuvant therapy for early disease. The antiprogestins and antiandrogens studied thus far have had only limited success in breast cancer clinical trials.
Breast cancer: current and future endocrine therapies. [2018]Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.
Endocrine therapy in post-menopausal women with metastatic breast cancer: From literature and guidelines to clinical practice. [2018]Current international guidelines recommend endocrine therapy as the initial treatment of choice in hormone receptor positive advanced breast cancer. Endocrine therapy has been a mainstay of hormone responsive breast cancer treatment for more than a century. To date it is based on different approaches,such as blocking the estrogen receptor through selective receptor estrogen modulators, depleting extragonadal peripheral estrogen synthesis by aromatase inhibitors or inducing estrogen receptor degradation using selective down-regulators. Despite estrogen and/or progesterone receptor positive status, up to a quarter of patients could be either primarily resistant to hormone therapies or will develop hormone resistance during the course of their disease. Different mechanisms, either intrinsic or acquired, could be implicated in endocrine resistance. In the present work available endocrine therapies and their appropriate sequences have been reviewed, and the most promising strategies to overcome endocrine resistance have been highlighted.
Improving Response to Hormone Therapy in Breast Cancer: New Targets, New Therapeutic Options. [2022]The majority of breast cancer expresses the estrogen and or progesterone receptors (ER and PR). In tumors without concomitant HER2 amplification, hormone therapy is a major treatment option for all disease stages. Resistance to hormonal therapy is associated with disease recurrence and progression. Recent studies have identified a number of resistance mechanisms leading to estrogen-independent growth of hormone receptor-positive (HR+) breast cancer as a result of genetic and epigenetic alterations, which could be exploited as novel therapeutic targets. These include acquired mutations in ER-alpha (ESR1) in response to endocrine deprivation; constitutive activation of cyclin-dependent kinases (CDK) 4 and 6; cross talk between ER and growth factor receptor signaling such as HER family members, fibroblast growth factor receptor (FGFR) pathways, intracellular growth, and survival signals PI3K/Akt/mTOR; and epigenetic modifications by histone deacetylase (HDAC) as well as interactions with tumor microenvironment and host immune response. Inhibitors of these pathways are being developed to improve efficacy of hormonal therapy for treatment of both metastatic and early-stage disease. Two agents are currently approved in the United States for the treatment of metastatic HR+ breast cancer, including the mTOR inhibitor everolimus and the CDK4/6 inhibitor palbociclib. Management of toxicity is a critical aspect of treatment; the primary toxicity of everolimus is stomatitis (treated with topical steroids) and of palbociclib is neutropenia (treated with dose reduction/delay). Many agents are in clinical trials, primarily in combination with hormone therapy; novel combinations are under active investigation.
Overcoming endocrine resistance in metastatic hormone receptor-positive breast cancer. [2019]Endocrine therapy has historically formed the basis of treatment of metastatic hormone receptor-positive breast cancer. The development of endocrine resistance has led to the development of newer endocrine drug combinations. Use of the CDK4/6 inhibitors has significantly improved progression-free survival in this group of patients. There are multiple studies of the use of P13K inhibitors and mTOR inhibitors for use as subsequent lines of therapy, particularly for endocrine resistance. The optimal sequencing of therapy should be based on medical comorbidities, prior adjuvant therapies, quality of life, side-effect profile, and disease-free interval.
Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease. [2022]Resistance to endocrine therapy remains a major clinical problem in the treatment of oestrogen-receptor positive (ER+) breast cancer. Studies show androgen-receptor (AR) remains present in 80-90% of metastatic breast cancers providing support for blockade of AR-signalling. However, clinical studies with abiraterone, which blocks cytochrome P450 17A1 (CYP17A1) showed limited benefit.
Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success. [2020]Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions.
Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). [2021]The advent of targeted therapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (HR+/HER2‑ aBC) provides a novel therapeutic approach other than endocrine therapy. One targeted signaling pathway and three immune‑checkpoints have been demonstrated to be in association with tumor proliferation and growth in HR+/HER2‑ aBC. A number of phosphoinositide 3‑kinase/AKT/mammalian target of rapamycin signaling pathway inhibitors demonstrate clinical activity against this tumor subtype. The CDK4/6 inhibitors as a single agent or in combination with endocrine therapy have produced promising tumor response with acceptable toxicity in patients with HR+/HER2‑ aBC. Programmed death 1/programmed death ligand 1 (PD1/PD‑L1) and cytotoxic T lymphocyte antigen‑4 inhibitors can also produce an antitumor immune response, which provides a proof‑of‑principle for the initial utilization of immunotherapy in breast cancer. The aim of the present review was to discuss the mechanisms of action, clinical efficacy and safety profiles of all the targeted biological therapies and immunotherapies that have been approved or are currently under evaluation for HR+/HER2‑ aBC.
Ribociclib plus fulvestrant in the treatment of breast cancer. [2021]Endocrine therapy (ET) is a standard first-line treatment for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have demonstrated significantly improved progression-free survival (PFS) with ET in patients with ABC. Recent reports indicate that the addition of the CDK4/6i ribociclib to ET, including fulvestrant, significantly improves PFS and overall survival (OS).
Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. [2022]Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes.