← Back to Search

CDK4/6 Inhibitor

ZEN003694 + Abemaciclib for Cancer

Phase 1
Recruiting
Led By Michael Cheng
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Dose Expansion Cohort Only: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN for age
Participants must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Must not have
Participants who have had cytotoxic chemotherapy, immunotherapy, or other investigational therapy within 2 weeks prior to entering the study. There is a two week required washout period for previous BET inhibitor therapy
Patients receiving any medications or substances that are Factor Xa inhibitors or Factor IIa inhibitors
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 5 years
Awards & highlights
No Placebo-Only Group

Summary

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.

Who is the study for?
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.
What is being tested?
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.
What are the potential side effects?
Possible side effects from ZEN003694 and abemaciclib may include fatigue, nausea, liver issues, blood count changes leading to infection risk increase or bleeding problems. There might also be risks related to taking pills and potential unknown effects on unborn babies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
My liver enzymes are within the normal range for my age.
Select...
My cancer is advanced, cannot be surgically removed, and standard treatments are not effective.
Select...
My kidney function, measured by creatinine levels or clearance, is within the required range.
Select...
I have been diagnosed with NUT carcinoma confirmed by specific lab tests.
Select...
I had hepatitis C but am cured, or I'm being treated with no detectable virus.
Select...
I am 16 or older and can care for myself, or if under 16, I can do most activities.
Select...
My brain metastases have been treated, stable for 1 month, and show no signs of getting worse.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I haven't had chemotherapy, immunotherapy, or experimental treatments in the last 2 weeks.
Select...
I am taking medication that affects blood clotting.
Select...
I am not taking strong medication that affects liver enzymes.
Select...
I do not have any severe ongoing illnesses or conditions that are not under control.
Select...
More than a quarter of my bone marrow has been exposed to radiation.
Select...
I am not taking strong medication that affects liver enzymes.
Select...
I haven't had a heart attack or unstable chest pain in the last 6 months.
Select...
I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.
Select...
I have not had major surgery in the last 3 weeks.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 5 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Clinical benefit rate (CBR) (Phase I dose expansion)
Duration of response (DoR) (Phase I dose expansion)
Incidence of adverse events (Phase I dose expansion)
+3 more
Secondary study objectives
Pharmacokinetics (PK)
Thymidine
Other study objectives
Analysis of ATAC-sequence data

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Biopsy
2014
Completed Phase 4
~1150
Biospecimen Collection
2004
Completed Phase 3
~2030
Abemaciclib
2019
Completed Phase 2
~1890

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
BET inhibitors, such as ZEN003694, work by targeting the bromodomain and extra-terminal (BET) proteins, which play a crucial role in regulating gene expression that promotes tumor growth. By inhibiting these proteins, BET inhibitors can reduce the proliferation of cancer cells. CDK4/6 inhibitors, like Abemaciclib, block cyclin-dependent kinases 4 and 6, which are essential for cell cycle progression from the G1 to the S phase. This inhibition results in cell cycle arrest and reduced tumor growth. These mechanisms are particularly important for Neuroendocrine Tumors (NETs) because they address the uncontrolled cell proliferation characteristic of these tumors, potentially leading to better disease management and improved patient outcomes.
Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer - the SONIA study: study protocol for a randomized controlled trial.The impact of ethnicity on efficacy and toxicity of cyclin D kinase 4/6 inhibitors in advanced breast cancer: a meta-analysis.

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,958 Previous Clinical Trials
41,112,550 Total Patients Enrolled
943 Trials studying Breast Cancer
1,443,132 Patients Enrolled for Breast Cancer
Michael ChengPrincipal InvestigatorDana-Farber - Harvard Cancer Center LAO
1 Previous Clinical Trials
55 Total Patients Enrolled
Jia LuoPrincipal InvestigatorDana-Farber - Harvard Cancer Center LAO
1 Previous Clinical Trials
55 Total Patients Enrolled

Media Library

Abemaciclib (CDK4/6 Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05372640 — Phase 1
Breast Cancer Research Study Groups: Treatment (ZEN003694, abemaciclib)
Breast Cancer Clinical Trial 2023: Abemaciclib Highlights & Side Effects. Trial Name: NCT05372640 — Phase 1
Abemaciclib (CDK4/6 Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05372640 — Phase 1
~7 spots leftby Jun 2025