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Renal Cell Carcinoma MetastaticPhase 1NCT03905889

A Study of Abemaciclib in Combination With Sunitinib in Metastatic Renal Cell Carcinoma

A Phase 1 study testing Abemaciclib and Sunitinib in people with Renal Cell Carcinoma Metastatic, run by Brown University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to determine the safety, tolerability, and maximal tolerated dose (MTD) of the combination of Abemaciclib and Sunitinib administered orally in patients with advanced and metastatic renal cell carcinoma. This study consists of two parts: Dose Escalation and Dose Expansion. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma Metastatic
What is being tested?
Abemaciclib and Sunitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
5 Jun 2019to 8 Mar 2022
Phase
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

  • Has histologic or cytologic evidence of metastatic renal cell carcinoma with histology predominantly (>50%) clear cell renal cell carcinoma solid neoplasm.
  • Has evidence of metastatic disease. Intermediate and poor risk patients according to International Metastatic Renal Cell Carcinoma Database criteria (IMDC) must have received prior combination ipilimumab and nivolumab therapy and subsequently experienced disease progression, or been offered ipilimumab and nivolumab combination therapy and refused, or be ineligible for combination ipilimumab and nivolumab therapy. Patients with favorable risk disease have no eligibility requirement for prior use of ipilimumab and nivolumab immunotherapy.
  • Intermediate and poor risk patients (according to IMDC criteria) must also have received prior cabozantinib therapy and subsequently experienced disease progression, or been offered cabozantinib therapy and refused, or be ineligible for cabozantinib therapy. Patients with favorable risk disease have no eligibility requirement for prior use of cabozantinib. Cytoreductive nephrectomy is allowed but not mandatory.
  • Has in the opinion of the investigator, a predicted life expectancy of more than 3 months.
  • Has presence of at least 1 lesion that is measurable or evaluable using RECIST v1.1. This is defined in at least one dimension as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT, MRI or calipers by clinical exam
  • Has either archival tissue for analysis or will require confirmation of disease with fresh biopsy. Tissue will not be required pre/post treatment for biomarker analysis.
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  • Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2.
  • Patients with central nervous system metastases must have received surgical and/or radiation treatment, the metastases must be neurologically stable, and patients must be off corticosteroids or receiving a stable low-dose regimen of corticosteroids (i.e., a daily dose of 10 mg or less of prednisone or equivalent) for at least 4 weeks prior to the first dose of study drug.
  • Has completed any prior anticancer treatment and must have recovered from any acute toxicities. The period between the last dose of prior treatment and the first dose of study drug treatment must be at least 1 week for radiotherapy, at least 3-4 weeks from prior VEGFR/mTOR/ or immunotherapy or any other tyrosine kinase inhibitor (TKI) therapy, and at least 4 weeks for treatment with investigational drugs
  • Must be able to swallow capsules and tablets.
  • Has adequate organ function (i.e. lung, liver, kidney, bone marrow), as evidenced by multiple laboratory value results within specific parameters.
  • Women of childbearing potential (WOCP) as defined as not surgically sterile or not postmenopausal) must have a negative result for a serum pregnancy test before study drug administration on cycle 1 day 1. WOCP must use a medically accepted method of contraception and must agree to continue use this method for the duration of the study and for 30 days after discontinuation of study drug.
  • If male, is surgically sterile, or, if capable of producing offspring, is currently using an approved method of birth control and agrees to continued use of this method for the duration of the study (and for 30 days after taking the last dose of study drug because of the possible effects on spermatogenesis).

Who cannot join

  • Predominately non-clear cell renal cell carcinoma histology (i.e. >50%)
  • Has had chemotherapy within 4 weeks or radiotherapy within 1 week prior to first dose of study drug or those who have not recovered from toxicities due to agents administered more than 4 weeks earlier.
  • Has ongoing or active infection requiring parenteral antibiotics.
  • Has uncontrolled hypertension despite adequate therapy (i.e., systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 90 mm Hg found on 2 separate occasions separated by 1 week).
  • Has diabetes mellitus with occurrence of more than 2 episodes of ketoacidosis in the 12 months prior to the first dose of study drug.
  • Has an active second malignancy other than curatively resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or other cancers for which they are treated with curative intent, and no known active disease in the 3 years prior to enrollment.
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  • Has a primary brain tumor or has brain metastases from a non-renal cell cancer.
  • Has a QTcF interval greater than 470 msec, has a known history of QTcF prolongation, or has a history of torsade de pointes.
  • Has a known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
  • Has a known history of pulmonary fibrosis or any other restrictive lung disorder.
  • Has any other concurrent conditions including a medical, psychiatric, or social condition that, in the opinion of the investigator, could preclude the patient's participation in the study, pose an undue medical hazard, or interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (New York Heart Association [NYHA] Class III or IV), cardiac arrhythmia, or acute coronary syndromes within 6 months of enrollment.
  • Has used an investigational drug within 4 weeks prior to first dose of study drug or is currently participating in another investigational study.
  • Has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery or bariatric surgery).
  • Has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Abemaciclib or Sunitinib.
  • Has previous use of a CDK4/6 kinase inhibitor (eg. ribociclib, palbociclib)
  • Has previous use of a PIM1 kinase inhibitor

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

Other trials in United States

About this study

Official title: Targeting PIM1 and CDK4/6 Kinases in Renal Cell Carcinoma (PICKRCC): A Phase Ib Study of Abemaciclib (VerzenioTM) in Combination With Sunitinib in Metastatic Renal Cell Carcinoma

The purpose of this study is to determine the safety, tolerability, and maximal tolerated dose (MTD) of the combination of Abemaciclib and Sunitinib administered orally in patients with advanced and metastatic renal cell carcinoma. This study consists of two parts: Dose Escalation and Dose Expansion. During the dose escalation phase, participants will be sequentially enrolled in a standard 3 x 3 dose escalation study design to receive oral Abemaciclib in Combination with Sunitinib. The purpose of this dose escalation is to determine the maximal tolerated dose based on assessment of any dose limiting toxicity. The Dose Expansion Phase will enroll additional participants at the established maximal tolerated dose to further evaluate safety, tolerability, as well as the pharmacokinetics and pharmacodynamics of this combination drug regimen.

Read the detailed description

Renal cell carcinoma (RCC) accounted for about 64, 000 new cancer diagnoses in the USA in 2018. Up to 30% of those diagnoses will be patients with metastatic disease. Additionally, up to 50% of patients who undergo partial or radical nephrectomy will develop metastatic disease.. There is no cure for metastatic RCC, thus, metastatic RCC represents a significant cancer burden. Numerous directed therapies are available to improve overall survival but these do not result in durable complete responses. However, recent pre-clinical studies of RCC have demonstrated that Abemaciclib, a CDK4/6 and PIM1 kinase inhibitor, induces rapid, dramatic, and sustained tumor regression when used in combination with Sunitinib.

Our objectives for this study are as follows:

Primary Objectives:

  • Determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the combination of Abemaciclib with Sunitinib for patients with metastatic renal cell carcinoma. Additionally, determine pharmacokinetics (serum trough levels) of Abemaciclib and Sunitinib at steady state.
  • Continued safety assessment of the combination of Abemaciclib and Sunitinib at the established maximum tolerated dose (i.e. the recommended Phase II dose)

Secondary Objectives:

Determine any anti-tumor activity in the dose expansion phase of the study. Tumor related activity will be assessed by:

  • Length of progression free survival
  • Disease response rate
  • Time to disease response
  • Disease control rate
  • Duration of response
  • Overall survival and progression free survival
Being tested
Abemaciclib, Sunitinib
Keywords
Renal cell carcinoma, Abemaciclib, Sunitinib
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • AbemaciclibDrug

    Also called Verzenio

    Subjects will by given oral Abemaciclib every 12 hours for 14 days followed by 7 days off (i.e. a 21 day cycle). The initial dose will be 100 mg (Dose level 1) followed by 150 mg (Dose Level 2) depending on tolerability and toxicity assessment of the combination of medications. If at Dose Level 1 subjects cannot tolerate the combination of medications, the Abemaciclib would not be increased, and the dose will remain stable at 100 mg (Dose Level -1).

  • SunitinibDrug

    Also called Sutent

    Subjects will take oral Sunitinib daily for the 21-day cycle. Dosing will be at 50 mg for both Dose Levels 1 and 2. If the combination of the 2 medications is not tolerated by Subjects at Dose Levels 1 a lower dose of Sunitinib (37.5 mg) will be given (Dose Level -1).

Study groups in NCT03905889
Study groupRoleWhat they receive
Experimental Abemaciclib and SunitinibExperimentalFor the dose escalation phase, Subjects will receive a 21-day cycle of continuous oral daily Sunitinib in combination with Abemaciclib every 12 hours for 14 days followed by 7 days off. Using a traditional 3 x 3 study design assessing dose limiting toxicity, if the initial prescribed dosing of these 2 medications (Dose Level 1) is tolerated by the first 3 subjects, the study will pause for a 30 day time period between cohorts to assess toxicity. If no dose limiting toxicity is identified, the next cohort of 3 new subjects will be treated at the next higher dose level (Dose Level 2). If the original cohort treated at Dose Level 1 do not tolerate the combination of medications, the medication regimen will be modified to a lower dose (Dose Level - 1). A dose expansion phase is included which will evaluate the combination of Abemaciclib in combination with Sunitinib when given at the maximum tolerated dose as determined from the from dose escalation phase.
Receives: Drug: Abemaciclib; Drug: Sunitinib

What is being measured

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

  1. Maximum tolerated dose (MTD)

    A standard 3+3 trial design will be used to determine the safest maximal tolerated dose of the combination of Abemaciclib with Sunitinib. Doses of each medication will be increased or decreased based on upon tolerability and assessment of any dose limiting toxicity(ies) that may occur in study subjects. Safety and toxicity will be evaluated using the NCI Common Toxicity Criteria.

    Measured: At the end of Cycle 1 (each cycle is 21 days)

  2. Continued Toxicity assessment of the maximum tolerated dose (i.e the recommended Phase II dose) of Abemaciclib and Sunitinib as determined from the from dose escalation phase.

    Continued safety assessment of the combination of Abemaciclib and Sunitinib when administered at the maximal tolerated dose (i.e. the recommended phase 2 dose)

    Measured: 44 days after the last dose of study drug

  3. Pharmacokinetic Assessment of Abemaciclib and Sunitinib trough levels at steady state

    Assessment of steady state trough levels of Abemaciclib and Sunitinib

    Measured: Days 8, 15, 21, 28, 35, 42, 56, 63, 77, 84, 98 (at the beginning and weekly during cycles 1 and 2, days 1 and 15 of cycles 3-5; a cycle is 21-days)

Secondary outcomes (6)

  1. Disease Control Rate

    The number of subjects achieving a response (complete response, partial response, stable disease) on the combination regimen of Abemaciclib and Sunitinib at 6, 12, 24, 36, 45, and 54 weeks post initiation of treatment.

    Measured: 54 weeks

  2. Progression Free Survival

    The duration of time from the date of start of treatment until the criteria for disease progression is met by RECIST v1.1 criteria.

    Measured: 3 years

  3. Overall Survival

    Overall Survival rate from initiation of Abemaciclib and Sunitinib to completion of the protocol prescribed drug regimen and required follow up time period.

    Measured: 3 years

  4. Median Progression Free Survival

    The median number of days of progression free survival from initiation of Abemaciclib and Sunitinib to completion of the protocol prescribed drug regimen and required follow up time period.

    Measured: 3 years

  5. Median Overall Survival

    The median number of days of survival from initiation of Abemaciclib and Sunitinib to completion of the protocol prescribed drug regimen and required follow up time period.

    Measured: 3 years

  6. Duration of Response

    The period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented

    Measured: 3 years

Timeline

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

  1. First posted5 Apr 2019
  2. Study start5 Jun 2019
  3. Primary completion8 Mar 2022
  4. Study completion8 Mar 2022

Why it stopped: Funding withdrawn

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
Model description
This is a single-arm, non-randomized prospective phase Ib study with expansion. The goal is to determine the maximal tolerated dose by assessing dose limiting toxicities. A classic "3+3" design is used. There are a total of 3 dose levels (level -1, 1, and 2) with dose level 1 as the starting dose. Once the maximum tolerated dose is established, a cohort of an additional 10 subjects will be enrolled at the established dose.
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03905889
Sponsor's protocol ID
BrUOG 411
Status last verified
Jun 2024
First submitted
3 Apr 2019
Last updated
25 Jun 2024
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 Phase 1 study testing Abemaciclib and Sunitinib in people with Renal Cell Carcinoma Metastatic, run by Brown University 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 13 inclusion and 16 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: stopped early, as of the sponsor's last update on 25 Jun 2024. 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?

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?

The study was stopped early (reason given: Funding withdrawn). Results are not available in the source record.

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?

Maximum tolerated dose (MTD) (time frame: At the end of Cycle 1 (each cycle is 21 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 NCT03905889.

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 25 Jun 2024.

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