Your session is about to expire
← 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 belowSelect...
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 weeks3 visits
Treatment ~ Varies
Follow Up ~ up to 5 years
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 5 years
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 moreSecondary 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.
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
Eligibility Criteria:
This trial includes the following eligibility criteria:- I had radiotherapy at least 2 weeks ago or stereotactic radiosurgery within the last week.My hemoglobin level is at least 8 g/dL, possibly after a transfusion.I am HIV positive, on treatment, and my viral load is undetectable.I haven't taken any TKIs or small molecule drugs recently.I haven't had a heart attack or unstable chest pain in the last 6 months.I have another cancer, but it won't affect this trial's treatment.I can swallow and keep down pills.My cancer is advanced, cannot be surgically removed, and standard treatments are not effective.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 had hepatitis C but am cured, or I'm being treated with no detectable virus.I am 12 years or older and weigh more than 40 kg if I'm under 18.My heart function is classified as NYHA class 2B or better.My liver enzymes are within the normal range for my age.I have recovered from chemotherapy side effects, except for possible hair loss or mild nerve pain.I am not taking strong medication that affects liver enzymes.I may have had surgery to remove a tumor.I have not had a bone-targeted radionuclide treatment in the last 6 weeks.My kidney function, measured by creatinine levels or clearance, is within the required range.More than a quarter of my bone marrow has been exposed to radiation.I do not have any severe ongoing illnesses or conditions that are not under control.I have a digestive issue that affects how my body absorbs medication.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.My cancer can be measured or evaluated according to specific criteria.I have chronic hepatitis B but it's undetectable with treatment.I have had various treatments for my cancer, including BET and CDK4/6 inhibitors.I am 16 or older and can care for myself, or if under 16, I can do most activities.I have been diagnosed with NUT carcinoma confirmed by specific lab tests.I finished my radiotherapy at least 14 days ago and have recovered from its immediate effects.I can understand and am willing to sign the consent form, or I have someone who can do it for me.My brain metastases have been treated, stable for 1 month, and show no signs of getting worse.
Research Study Groups:
This trial has the following groups:- Group 1: Treatment (ZEN003694, abemaciclib)
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.