Ribociclib and Gemcitabine Hydrochloride in Treating Patients With Advanced or Metastatic Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03237390|
Recruitment Status : Active, not recruiting
First Posted : August 2, 2017
Last Update Posted : October 7, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm||Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Ribociclib||Phase 1|
I. To describe the dose-limiting toxicities and identify the maximum tolerated dose (MTD) and recommended phase II dose of the combination of ribociclib and gemcitabine hydrochloride (gemcitabine) in patients with advanced solid tumors.
I. To describe the safety and tolerability of the combination of ribociclib and gemcitabine.
II. To describe the pharmacokinetic (PK) of ribociclib in combination with gemcitabine.
III. To describe preliminary evidence of efficacy of the combination of ribociclib and gemcitabine.
I. To evaluate the correlation of CDK4/6, cyclin D1 and cyclin D3 amplification, retinoblastoma (RB) and P16 expression in archived and biopsied tumor tissue with treatment response.
OUTLINE: This is a dose-escalation study.
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and ribociclib orally (PO) once daily (QD) on days 8-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of CDK4/6 Inhibitor Ribociclib (LEE011) Combined With Gemcitabine in Patients With Advanced Solid Tumors|
|Actual Study Start Date :||January 4, 2018|
|Estimated Primary Completion Date :||August 9, 2022|
|Estimated Study Completion Date :||August 9, 2022|
Experimental: Treatment (gemcitabine hydrochloride, ribociclib)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and ribociclib PO QD on days 8-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose [ Time Frame: Up to 21 days ]Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 2 patients (out of 6).
- Best response defined as best objective status recorded from the start of the treatment until disease progression/recurrence [ Time Frame: Up to 18 months ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group). The number of responses may indicate further evaluation for specific tumor types in a phase II setting.
- Confirmed response defined to be a stringent complete response, complete response, very good partial response, or partial response [ Time Frame: Up to 18 months ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group). The number of responses may indicate further evaluation for specific tumor types in a phase II setting.
- Incidence of adverse events [ Time Frame: Up to 30 days after last dose ]Number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized. Adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence
- Pharmacokinetic (PK) of ribociclib [ Time Frame: Pre-ribociclib dose, 0.5, 1, 2, 4, 6, and 8 hours post dose on days 8 and 14 course 1 and pre-gemcitabine hydrochloride dose on day 1 course 2 ]A population PK model will be developed utilizing the PK time points collected, and then used to estimate individual area under the curves or clearance of ribociclib in combination with gemcitabine hydrochloride. The effect of the combination on PK of each drug will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics.
- CDK2/4/6, Cyclin D1 and Cyclin D3 amplification, retinoblastoma (RB) and P16 expression [ Time Frame: Up to 18 months ]CDK2/4/6, Cyclin D1 and Cyclin D3 amplification, RB and P16 expression in archived and biopsied tumor tissue with be correlated with treatment response.
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): NCT03237390
|United States, Arizona|
|Mayo Clinic Hospital|
|Phoenix, Arizona, United States, 85054|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Alex Adjei||Mayo Clinic|