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Metastatic Microsatellite Stable Colorectal CarcinomaPhase 1NCT06654037

Testing the Addition of an Anti-Cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (5-Fluorouracil) for Metastatic, Refractory Colorectal Cancer

A Phase 1 study testing Abemaciclib, Biopsy Procedure and Biospecimen Collection in people with Metastatic Microsatellite Stable Colorectal Carcinoma and Refractory Microsatellite Stable Colorectal Carcinoma, run by National Cancer Institute (NCI) at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase I trial tests the safety, side effects, and best dose of abemaciclib in combination with 5-fluorouracil and how well it works in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has not responded to… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Abemaciclib, Biopsy Procedure and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
8 sitesUnited States
Study dates
18 Apr 2025to 1 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed microsatellite stability (MSS) metastatic colorectal cancer where patients have progressed on standard therapies which would have included 5-FU or capecitabine, oxaliplatin, and irinotecan. Patients must have had progression of disease (PD) or intolerance to bevacizumab and anti-EGFR antibodies (cetuximab or panitumumab) in patients who have left-sided and RAS-wildtype CRC
  • Patients must have measurable disease
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of abemaciclib in combination with 5-FU in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1,500/mcL
Show all 27Show fewer
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN for patients who do not have liver metastases, and ≤ 5 x institutional ULN for patients with liver metastases
  • Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
  • Patients must have available archival tumor tissue at the time of patient enrollment for molecular profiling studies. A biopsy may be done if archival tissue is not available
  • Palliative radiation for symptom management to a metastatic site will be permitted during the course of the study. Please discuss specific cases with the national principal investigator (PI)
  • Patients must have completed previous systemic therapy for at least five half-lives or 2 weeks, whichever is shorter, prior to study dosing
  • Patients who have not had major surgery within 14 days prior to randomization
  • Patients who do not have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance < 30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
  • Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization
  • Patients who are able to swallow oral medications
  • Patients who do not have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
  • Patients who do not have an active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment) or fungal infection
  • The effects of abemaciclib on the developing human fetus are unknown. For this reason and because cyclin-dependent kinases (CDK) inhibiting agents as well as other therapeutic agents used in this trial are known to be teratogenic, men and women treated or enrolled on this protocol must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to the study, for the duration of study participation, and 3 months after completion of abemaciclib and fluorouracil. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Who cannot join

  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia or grade 2 peripheral neuropathy. Patients who are experiencing immune related adverse events (AEs) which are adequately treated with hormone replacement therapy, including diabetes on insulin regimen, hypothyroidism on levothyroxine, and adrenal insufficiency on steroid replacement will also be eligible
  • Patients who are receiving any other investigational agents. There is to be a washout period of two weeks or five half-lives, whichever is shorter, for all investigational agents prior to treatment initiation on this study. Individual cases can be discussed with the national PI
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or other agents (5-FU) used in study such as a previous intolerance to 5-FU or capecitabine, including patients with known or suspected dihydropyrimidine dehydrogenase deficiency
  • Patients who have received previous treatment with a CDK4/6 inhibitor
  • Patients with a gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication
  • Patients with peritoneal metastases complicated by ascites which are refractory to diuretic therapy and requires therapeutic paracenteses more than once every 2 weeks
Show all 9Show fewer
  • Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A enzymes before enrollment or while on protocol therapy are ineligible. Patients receiving moderate CYP3A inhibitors or inducers will be monitored. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • Pregnant women are excluded from this study because abemaciclib is a CDK-inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with abemaciclib, breastfeeding should be discontinued if the mother is treated with abemaciclib. These potential risks may also apply to other agents used in this study

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

8 sites in 1 country

United States8 sites, 8 recruiting

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

    Site Public Contact, 513-584-7698, cancer@uchealth.com

    Davendra P. Sohal

    Recruiting

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Farshid Dayyani

    Recruiting

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Farshid Dayyani

    Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Site Public Contact, 412-647-8073

    Janie Y. Zhang

    Recruiting

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Chaoyuan Kuang

    Recruiting

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Chaoyuan Kuang

    Recruiting

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Chaoyuan Kuang

    Recruiting

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

    Site Public Contact, 513-584-7698, cancer@uchealth.com

    Davendra P. Sohal

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1 Study of 5-Fluorouracil in Combination With Abemaciclib in Metastatic, Refractory CRC

This phase I trial tests the safety, side effects, and best dose of abemaciclib in combination with 5-fluorouracil and how well it works in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has not responded to treatment (refractory). Abemaciclib, a type of cyclin-dependent kinase inhibitor, blocks certain proteins, which may help keep tumor cells from growing. 5-fluorouracil, a type of antimetabolite, stops cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Giving abemaciclib in combination with 5-fluorouracil may be safe, tolerable, and/or effective in treating patients with metastatic and refractory colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety and tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of abemaciclib in combination with 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC).

SECONDARY OBJECTIVES:

  1. To estimate the anti-tumor activity of abemaciclib in combination with 5-FU. II. To determine the pharmacodynamics (PD) of abemaciclib in combination with 5-FU (death receptor 5 [DR5] dynamics and apoptosis).

III. To identify molecular subpopulations particularly sensitized to abemaciclib and 5-FU.

IV. To determine the pharmacokinetics (PK) of abemaciclib and 5-FU.

EXPLORATORY OBJECTIVES:

  1. To explore exposure-response relationships for abemaciclib and 5-FU. II. To evaluate circulating tumor DNA (ctDNA) as a predictor for treatment response to therapy.

OUTLINE: This is a dose-escalation study of abemaciclib in combination with 5-FU followed by a dose-expansion study.

Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28 and 5-FU intravenously (IV) over 46 hours on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and radiologic imaging throughout the study and may additionally undergo a tissue biopsy before treatment and on cycle 1 day 16.

After completion of study treatment, patients are followed up every 3 months for 6 months.

Being tested
Abemaciclib, Biopsy Procedure, Biospecimen Collection, Fluorouracil, Radiologic Imaging Procedure
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbemaciclibDrug

    Also called LY 2835219, LY-2835219, LY2835219, Verzenio

    Given PO

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Radiologic Imaging ProcedureProcedure or surgery

    Undergo radiologic imaging

Study groups in NCT06654037
Study groupRoleWhat they receive
Treatment (abemaciclib, 5-FU)ExperimentalPatients receive abemaciclib PO BID on days 1-28 and 5-FU IV over 46 hours on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and radiologic imaging throughout the study and may additionally undergo a tissue biopsy before treatment and on cycle 1 day 16.
Receives: Drug: Abemaciclib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Fluorouracil; Procedure: Radiologic Imaging Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (DLT)

    Will be tabulated using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each dose level.

    Measured: Within first cycle (cycle length = 28 days)

  2. Maximum tolerated dose (MTD)

    MTD will be the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.

    Measured: Up to completion of dose-escalation phase

  3. Incidence of adverse events

    Will be evaluated using CTCAE v 5.0 and will be tabulated for each dose level.

    Measured: Up to 30 days after last dose of study treatment

Secondary outcomes (8)

  1. Objective response rate (ORR)

    ORR will be defined as the addition of complete response and partial response. Response will be assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. The probability of ORR will be estimated with exact 95% binomial confidence intervals.

    Measured: Up to 6 months post-treatment

  2. Clinical benefit rate

    Will be assessed using RECIST v 1.1.

    Measured: Up to 6 months post-treatment

  3. Progression free survival (PFS)

    PFS will be assessed using the Kaplan-Meier method, along with 95% confidence interval.

    Measured: From the start of treatment to time of progression or death, assessed up to 6 months post-treatment

  4. Ribonucleic acid sequencing of death receptor 5

    Pre-post comparisons will be made within patients being biopsied, using a non-parametric paired test, at a significance level (alpha) of 0.05.

    Measured: At pre-treatment on cycle 1 day 16

  5. Apoptosis by Pharmacodynamics Assay Development & Implementation Section lab

    Pre-post comparisons will be made within patients being biopsied, using a non-parametric paired test, at a significance level (alpha) of 0.05.

    Measured: At pre-treatment cycle 1 day 16

  6. Whole exome sequencing of archival tissue

    Will look for mutations in genes relevant to deoxyribonucleic acid (DNA) damage repair, signaling and (fluoropyrimidine) metabolism and in a descriptive manner evaluate any relations with peculiar response and/or toxicity.

    Measured: Up to cycle 1 day 1 pre-dose

  7. Pharmacokinetics (PK) of abemaciclib and possibly active metabolites M2, M20, and M18 in plasma and tumor tissue

    Abemaciclib PK will be evaluated and compared descriptively with historical data.

    Measured: At pre-dose on cycle 1 days 1, 2, 8, and 15 and at cycle 2 days 1 and 15

  8. PK of 5-fluorouracil (5-FU)

    Will be evaluated by area under the concentration-time curve (AUC) and be compared descriptively with historical data.

    Measured: At cycle1 day 1 pre-dose and cycle 1 day 2 (22-26 hours post start of 5-FU infusion)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2024
  2. Study start18 Apr 2025
  3. Primary completion1 Apr 2027 (estimated)
  4. Study completion1 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06654037
Sponsor's protocol ID
NCI-2024-08691
Other IDs
NCI-2024-08691, 10670, 10670, UM1CA186690
Status last verified
Oct 2026
First submitted
22 Oct 2024
Last updated
15 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Abemaciclib, Biopsy Procedure and Biospecimen Collection in people with Metastatic Microsatellite Stable Colorectal Carcinoma and Refractory Microsatellite Stable Colorectal Carcinoma, run by National Cancer Institute (NCI) at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (DLT) (time frame: Within first cycle (cycle length = 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06654037.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.

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