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

  • STATUS
    Recruiting
  • End date
    Nov 5, 2024
  • participants needed
    22
  • sponsor
    Milton S. Hershey Medical Center
Updated on 27 January 2021

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. 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.

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

Details
Condition Renal Cell Carcinoma Metastatic
Treatment Sunitinib, Abemaciclib
Clinical Study IdentifierNCT03905889
SponsorMilton S. Hershey Medical Center
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Renal Cell Carcinoma Metastatic?
Do you have any of these conditions: Do you have Renal Cell Carcinoma Metastatic??
Do you have any of these conditions: Do you have Renal Cell Carcinoma Metastatic??
Do you have any of these conditions: Do you have Renal Cell Carcinoma Metastatic??
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
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)

Exclusion Criteria

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
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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note