A Study of Abemaciclib in Combination With Sunitinib in Metastatic Renal Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT03905889|
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : November 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma Metastatic||Drug: Abemaciclib Drug: Sunitinib||Phase 1|
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:
- 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)
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|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|
|Actual Study Start Date :||June 5, 2019|
|Estimated Primary Completion Date :||November 5, 2021|
|Estimated Study Completion Date :||November 5, 2024|
Experimental: Experimental Abemaciclib and Sunitinib
For 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.
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).
Other Name: Verzenio
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).
Other Name: Sutent
- Maximum tolerated dose (MTD) [ Time Frame: At the end of Cycle 1 (each cycle is 21 days) ]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.
- 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. [ Time Frame: 44 days after the last dose of study drug ]Continued safety assessment of the combination of Abemaciclib and Sunitinib when administered at the maximal tolerated dose (i.e. the recommended phase 2 dose)
- Pharmacokinetic Assessment of Abemaciclib and Sunitinib trough levels at steady state [ Time Frame: 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) ]Assessment of steady state trough levels of Abemaciclib and Sunitinib
- Disease Control Rate [ Time Frame: 54 weeks ]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.
- Progression Free Survival [ Time Frame: 3 years ]The duration of time from the date of start of treatment until the criteria for disease progression is met by RECIST v1.1 criteria.
- Overall Survival [ Time Frame: 3 years ]Overall Survival rate from initiation of Abemaciclib and Sunitinib to completion of the protocol prescribed drug regimen and required follow up time period.
- Median Progression Free Survival [ Time Frame: 3 years ]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.
- Median Overall Survival [ Time Frame: 3 years ]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.
- Duration of Response [ Time Frame: 3 years ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905889
|Contact: Clinical Research Coordinator RN (Penn State Cancer Institute Genitourinary Oncology Division)||717 531 5471||PSCI-CTO@pennstatehealth.psu.edu|
|United States, Pennsylvania|
|Penn State Cancer Institute||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Sheldon L. Holder, MD, PhD firstname.lastname@example.org|
|Principal Investigator:||Sheldon Holder, MD, PhD||Penn State Cancer Institute|