Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests the safety and best dose of two drugs, ZEN003694 and abemaciclib, in patients with advanced cancers. These drugs work together to stop cancer cells from growing and dividing. The goal is to find out if this combination can help treat cancers that have spread or cannot be removed by surgery.
What data supports the idea that ZEN003694 + Abemaciclib for Cancer is an effective treatment?The available research shows that Abemaciclib, when used with other therapies, is effective in treating certain types of breast cancer. For example, in a study, Abemaciclib combined with endocrine therapy reduced the risk of breast cancer coming back in patients with a high risk of recurrence. Another study found that adding Abemaciclib to letrozole improved the time patients lived without the cancer getting worse compared to those who did not receive Abemaciclib. These findings suggest that Abemaciclib is a valuable option for treating specific breast cancers, although there is no direct data on ZEN003694 combined with Abemaciclib.127910
Is the drug Abemaciclib a promising treatment for cancer?Yes, Abemaciclib is a promising drug for cancer. It has been shown to reduce the risk of breast cancer recurrence when combined with other therapies. It also works well with other treatments to enhance its cancer-fighting effects.25689
What safety data exists for the treatment ZEN003694 + Abemaciclib for cancer?The safety data for Abemaciclib, also known as Verzenio, includes its use in combination with endocrine therapy for hormone receptor-positive, HER2-negative breast cancer. Common adverse events reported include diarrhea, infections, and neutropenia. These side effects are considered manageable. The MONARCH trials provide detailed safety analyses, highlighting dose-dependent early-onset diarrhea and the management of adverse events in advanced breast cancer. However, specific safety data for the combination of ZEN003694 and Abemaciclib is not detailed in the provided research.12349
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications, but you cannot take strong inhibitors or inducers of CYP3A4 enzymes. These must be stopped at least 7 days before starting the trial. Proton pump inhibitors are not allowed, and if you use H2 blockers or antacids, a staggered dosing schedule is required. Always consult with your doctor about your specific medications.
Eligibility Criteria
This trial is for adults and kids aged 12-17 with NUT carcinoma or other solid tumors that have spread or can't be surgically removed. Participants need to meet specific health criteria, like normal organ function tests, controlled HIV or hepatitis if present, and a certain level of physical fitness. They should not have untreated brain metastases or conditions that could affect the trial's results.Inclusion Criteria
My liver enzymes are within the normal range for my age.
My cancer is advanced, cannot be surgically removed, and standard treatments are not effective.
My kidney function, measured by creatinine levels or clearance, is within the required range.
I have been diagnosed with NUT carcinoma confirmed by specific lab tests.
I had hepatitis C but am cured, or I'm being treated with no detectable virus.
I am 16 or older and can care for myself, or if under 16, I can do most activities.
My brain metastases have been treated, stable for 1 month, and show no signs of getting worse.
Exclusion Criteria
I haven't had chemotherapy, immunotherapy, or experimental treatments in the last 2 weeks.
I am taking medication that affects blood clotting.
I am not taking strong medication that affects liver enzymes.
I do not have any severe ongoing illnesses or conditions that are not under control.
More than a quarter of my bone marrow has been exposed to radiation.
I am not taking strong medication that affects liver enzymes.
I haven't had a heart attack or unstable chest pain in the last 6 months.
I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.
I have not had major surgery in the last 3 weeks.
Treatment Details
The trial is testing the combination of two drugs: ZEN003694 (a BET protein growth inhibitor) and abemaciclib (an enzyme blocker stopping tumor cell growth). It aims to find the safest dose that might help shrink or stabilize these cancers. The study includes biospecimen collection, imaging, and biopsies.
1Treatment groups
Experimental Treatment
Group I: Treatment (ZEN003694, abemaciclib)Experimental Treatment5 Interventions
Patients receive ZEN003694 PO QD on days 1-28 or 5 days on and 2 days off, and abemaciclib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo imaging evaluation, blood sample collection and tumor biopsy throughout the study.
Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Verzenio for:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
🇪🇺 Approved in European Union as Verzenio for:
- HR+, HER2- advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Los Angeles County-USC Medical CenterLos Angeles, CA
Dana-Farber - Harvard Cancer Center LAOBoston, MA
USC / Norris Comprehensive Cancer CenterLos Angeles, CA
Keck Medicine of USC KoreatownLos Angeles, CA
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]Interim data from the MONARCH3 study indicate that abemaciclib is an effective first-line therapy for advanced ER-positive, HER2-negative breast cancer. Adding the investigational CDK4/6 inhibitor to letrozole significantly improved patients' progression-free survival, compared with those given a placebo alongside endocrine therapy.
Abemaciclib: First Global Approval. [2019]Abemaciclib (Verzenio™) is an orally administered inhibitor of cyclin-dependent kinases 4 and 6 that is being developed by Eli Lilly and Company. Abemaciclib has been approved in the USA for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, in combination with fulvestrant in women with disease progression following endocrine therapy, and as monotherapy in adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. In addition, abemaciclib is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of abemaciclib leading to its first approval for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. [2023]Abemaciclib demonstrated efficacy in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Here we provide a comprehensive summary of the most common adverse events (AEs), their management, and whether AEs or dose reductions influenced progression-free survival (PFS), in the MONARCH 2 and 3 trials.
nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. [2021]Label="BACKGROUND">Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy.
Patient-Reported Outcomes Predict Progression-Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib. [2022]Abemaciclib is a CDK4/6 inhibitor used to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The prognostic value of patient-reported outcomes (PROs) has been minimally explored for treatment outcomes with CDK4/6 inhibitors. The performance of PROs compared with Eastern Cooperative Oncology Group performance status (ECOG-PS) is unknown.
Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]Abemaciclib is an oral, selective small-molecule CDK 4 and 6 inhibitor. In preclinical models, abemaciclib synergized with programmed cell death protein-1 blockade to enhance antitumor efficacy. Here, we report the safety and anticancer activity of abemaciclib plus pembrolizumab in two cohorts with NSCLC.
An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. [2022]Abemaciclib is a new oral targeted treatment option for patients with advanced breast cancer. The emerging field of oral antitumor therapeutics presents challenges for both patients and healthcare teams; non-adherence and high inter-individual pharmacokinetic variability can influence response rates.
Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. [2022]Cyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen.
Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.
Abemaciclib in Combination with Endocrine Therapy for Adjuvant Treatment of Hormone Receptor-Positive, HER2-Negative, Node-Positive Early Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. [2023]The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Eli Lilly) of abemaciclib (Verzenios) to submit evidence for the clinical and cost effectiveness of this drug in combination with endocrine therapy (ET) for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence, as part of the Institute's Single Technology Appraisal (STA) process. Kleijnen Systematic Reviews Ltd, in combination with Newcastle University, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarised the Company Submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The ERG produced a critical review of the evidence for the clinical and cost-effectiveness evidence in the CS and also independently searched for relevant evidence and modified the manufacturer decision analytic model to examine the impact of altering some of the key assumptions. A systematic literature review identified the MonarchE trial, an ongoing, open-label, randomised, double blind trial involving 5637 people comparing abemaciclib in combination with ET versus ET alone. The trial included two cohorts that used different inclusion criteria to define high risk of recurrence. The ERG considered Cohort 1 as an adequate representation of this population and the AC concluded that Cohort 1 was generalisable to National Health Service clinical practice. Trial results showed improvements in invasive disease-free survival for the abemaciclib arm, which was considered an appropriate surrogate outcome. The ERG believed that the modelling structure presented in the de novo economic model by the company was appropriate but highlighted several areas of uncertainty that had the potential to have a significant impact on the resulting incremental cost-effectiveness ratio (ICER). Areas of uncertainty included the extrapolation of long-term survival curves, the duration of treatment effect and treatment waning, and the proportion of patients who receive other CDK4/6 treatments for metastatic disease after receiving abemaciclib. ICER estimates were £9164 per quality-adjusted life-year gained for the company's base-case and £17,810 for the ERG's base-case. NICE recommended abemaciclib with ET as an option for the adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.