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Colorectal CarcinomaEarly Phase 1NCT04870034

Binimetinib and Palbociclib Before Surgery for the Treatment of Operable KRAS-Positive Lung, Colorectal, or Pancreatic Cancer

A Early Phase 1 study testing Binimetinib, Palbociclib and Therapeutic Conventional Surgery in people with Colorectal Carcinoma and Lung Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This early phase I trial studies the direct effects on cancer cells of the drugs binimetinib and palbociclib, in patients with KRAS-positive lung, colorectal, or pancreatic cancer that can be removed by surgery (operable). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Binimetinib, Palbociclib and Therapeutic Conventional Surgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
15 Jan 2024to 30 Sep 2026
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • Age >= 18 years of age
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Patients with verified and operable KRAS-positive mutant lung adenocarcinoma, colorectal, or pancreatic cancer
  • Have available diagnostic, pre-treatment archival tumor tissue
  • Medically fit for surgical resection
  • Absolute neutrophil count (ANC) >= 1500/ uL
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  • Hemoglobin (Hgb) >= 9 g/dL
  • Platelet count >= 100,000/uL
  • Total bilirubin =< 1.5 x ULN (upper limit of normal)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x ULN
  • Creatinine clearance > 60 mL/min (Cockcroft-Gault Equation)
  • Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
  • Ability to swallow and retain oral medication
  • Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and to not donate ova from screening until 30 days after the last dose of study drug. 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
  • Male participants must agree to use methods of contraception that are highly effective or acceptable, and to not donate sperm from screening until 90 days after the last dose of study drug
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

  • Prior therapy with a CDK4/6 (e.g. palbociclib, ribociclib) or MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib)
  • Participants who have had any other systemic anticancer therapy within 2 weeks prior to entering the study
  • Is currently participating in a study and receiving an investigational agent; has received an investigational agent within 14 days prior to start of study treatment
  • Participants who have undergone major surgery =< 6 weeks prior to start of study treatment or who have not recovered from side effects of such procedure
  • Patient has not recovered to =< grade 1 from toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (=< grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll
  • Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. Note: Patients with previously treated brain metastases may participate provided they are stable (e.g., without evidence of progression by radiographic imaging for at least 28 days before the first dose of study treatment and neurologic symptoms have returned to baseline), and have no evidence of new or enlarging brain metastases or central nervous system (CNS) edema, and does not require steroids at least 7 days before the first dose of study treatment
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Impaired cardiovascular function or clinically significant cardiac diseases including, but not limited to, any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to screening
  • Congestive heart failure requiring treatment (New York Heart Association grade >= 2)
  • Left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition scan (MUGA) or echocardiography (ECHO)
  • Uncontrolled hypertension defined as persistent systolic blood pressure >= 150 mmHg or diastolic blood pressure >= 100 mmHg despite current therapy
  • History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)
  • Baseline corrected QT (QTc) interval >= 480 ms
  • Impairment of gastrointestinal function or disease which may significantly alter the absorption of binimetinib or palbociclib (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (=< 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs
  • Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CPK) (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
  • Current use of a prohibited medication (including herbal medications, supplements, or foods) or use of a prohibited medication =< 1 week prior to the start of study treatment
  • History of or cerebrovascular events =< 12 weeks prior to the first dose of study treatment
  • History of pulmonary embolism (PE) with hemodynamic instability =< 12 weeks prior to first dose of study treatment. Note: Patients with PE that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of therapeutic anticoagulants for at least 4 weeks. Also, patients with deep vein thrombosis on stable dose of therapeutic anticoagulants for at least 4 weeks are allowed to participate in the study
  • Concurrent or previous other malignancy that requires active anticancer therapy
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Note: Patients with laboratory evidence of cleared HBV or HCV infection may be enrolled
  • Note: Patients with no prior history of HBV infection who have been vaccinated against HBV and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may be enrolled
  • Known history of acute or chronic pancreatitis =< 6 months prior to enrollment
  • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) =< 12 months prior to enrollment
  • Known hypersensitivity to the components of study drugs or its analogs
  • Pregnant or nursing female participants
  • Unwilling or unable to follow protocol requirements
  • Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study
  • The following special populations will not be included in the study:
  • Cognitively impaired adults/adults with impaired decision-making capacity
  • Individuals who are not yet adults (infants, children, teenagers)
  • Pregnant women
  • Prisoners

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Perioperative Analysis of Binimetinib and Palbociclib in RAS-Driven Tumors

This early phase I trial studies the direct effects on cancer cells of the drugs binimetinib and palbociclib, in patients with KRAS-positive lung, colorectal, or pancreatic cancer that can be removed by surgery (operable). Binimetinib and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and palbociclib may halt the growth of cancer cells and improve access of the immune system cells, a patient's own cells that fight infection and cancer, into the tumor.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the on-target efficacy of binimetinib and palbociclib in patients with operable RAS-mutant lung adenocarcinoma, colorectal, or pancreatic cancer.

SECONDARY OBJECTIVES:

  1. Correlative analysis of gene expression analysis. II. Define immune subsets within the pre and post-treatment tumor tissue.

OUTLINE:

Patients receive palbociclib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) for 14 days in the absence of disease progression or unacceptable toxicity. Within 1 week after last dose of study medication, patients undergo surgery.

After completion of study treatment, patients are followed up at 30 days.

Medical subject headings
Colorectal Neoplasms, Adenocarcinoma of Lung, Pancreatic Neoplasms

What participants receive

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

  • BinimetinibDrug

    Also called ARRY-162, ARRY-438162, MEK162, Mektovi

    Given PO

  • PalbociclibDrug

    Also called 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991

    Given PO

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgery

Study groups in NCT04870034
Study groupRoleWhat they receive
Treatment (palbociclib, binimetinib)ExperimentalPatients receive palbociclib PO QD and binimetinib PO BID for 14 days in the absence of disease progression or unacceptable toxicity. Within 1 week after last dose of study medication, patients undergo surgery.
Receives: Drug: Binimetinib; Drug: Palbociclib; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Change in Ki67 labeling index of > 70%

    Pathologic response by change in Ki-67% from pre and surgical biopsies

    Measured: Up to 30 days post treatment

  2. Incidence of adverse events

    Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by attribution and grade using frequencies and relative frequencies.

    Measured: Up to 30 days post-treatment

Secondary outcomes (2)

  1. Gene expression analysis

    Correlative analysis of gene expression analysis will focus on suppression of MEK and CDK4/6 regulated genes and induction of gene expression programs related to antigen presentation and inflammation.

    Measured: Up to 30 days post-treatment

  2. Immune subsets within the pre and posttreatment tumor tissue

    Multispectral imaging will be employed to define immune subsets within the pre and posttreatment tumor tissue with an emphasis on approaches to exploit the response to drug with immunologically active agents.

    Measured: Up to 30 days post-treatment

Timeline

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

  1. First posted3 May 2021
  2. Study start15 Jan 2024 (estimated)
  3. Primary completion30 Sep 2025 (estimated)
  4. Study completion30 Sep 2026 (estimated)

Why it stopped: Issues recruiting

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04870034
Sponsor's protocol ID
I 797920
Other IDs
NCI-2021-02908, I 797920
Status last verified
Dec 2023
First submitted
27 Apr 2021
Last updated
22 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Binimetinib, Palbociclib and Therapeutic Conventional Surgery in people with Colorectal Carcinoma and Lung Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site 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 16 inclusion and 36 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: withdrawn, as of the sponsor's last update on 22 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Ki67 labeling index of > 70% (time frame: Up to 30 days post treatment). The study lists 2 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 NCT04870034.

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 22 Dec 2023.

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