Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma

Early Phase 1

Completed

Conditions: Carcinoma, Renal Cell

Interventions: Drug: Pazopanib
Other: Low Fat Diet

Registration Number: NCT02729194

Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary: Pazopanib is an orally administered multi-kinase inhibitor targeting VEGFR (vascular endothelial growth factor receptor), PDGFR (platelet derived growth factor) and c-kit, which are critical to growth and proliferation of neoplastic cells. Pazopanib has been FDA approved for advanced renal cell carcinoma (RCC) with a clear cell component. Conventional Pazopanib dosing WITHOUT FOOD is with an initial dose of 800 mg by mouth daily. Investigators hypothesize that administration of pazopanib with low fat meal would be safe and feasible with secondary implications of higher pazopanib levels; potentially translating into greater anti-tumor efficacy in advanced renal cell cancer, with significant cost savings. In the proposed pilot study, investigators seek to test the feasibility and practicality of this approach and gather preliminary data on adverse effects and the safety profile. Investigators hope to ameliorate any potential for greater toxicities with a dynamic dosing design that incorporates adverse events from each cycle into dosing for the next cycle and a structured symptom specific plan.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Adult (>18 years of age) with unresectable locally advanced or metastatic renal cell carcinoma with a clear cell component.
Subjects must have measurable disease per RECIST 1.1 criteria.
Subjects must not have had prior pazopanib therapy.
Subjects must have an ECOG (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.) performance status of less than or equal to 2.
Up to 3 lines of prior VEGF (vascular endothelial growth factor) or VEGFR (vascular endothelial growth factor receptor) targeted therapy are permitted. Any prior therapy should have been completed ≥ 2 weeks prior to start of study therapy.
Subjects may have received any number of the following therapies: cytokine therapy (e.g. high dose interleukin-2) or checkpoint inhibitor therapy (e.g. anti-PD1/PDL1, anti-CTLA4) or mTOR inhibitor therapy (e.g. everolimus, temsirolimus).
Adequate organ and marrow function (Absolute neutrophil count > 1000/mm3, platelets > 100,000/mm3, aspartate aminotransferase/ alanine aminotransferase/ total bilirubin < 1.5 X ULN (upper limit of normal). Patients with Gilbert's disease are exempt.
Subject must be willing and able to take pazopanib with a low-fat meal every day as specified in the protocol.
Subjects must be willing and able to come off any PPI(proton pump inhibitor)/other strong CYP3A4 inhibitors or inducers/simvastatin.
Ability to understand and the willingness to sign a written informed consent.
All subjects, including those who are surgically sterilized, must be willing to use an effective method of contraception.

Exclusion Criteria

Any concurrent health condition that in the view of the treating physician would pose excessive risk to the patient if enrolled in the study.
Subjects with a history of hemoptysis, cerebral hemorrhage, clinically significant GI hemorrhage, myocardial infarction within the past 6 months.
Patients at significant risk for GI (gastrointestinal) perforation or fistula.
Pregnant or nursing mothers.
Untreated CNS (central nervous system) metastasis. If treated CNS metastasis/es, treatment of CNS disease (surgery or radiation) must have been completed at least 30 days prior to registration. Patients could still be on steroids.
Subjects with known history of Cirrhosis, HIV, Hepatitis B or C.
Averaged QTc baseline in 3 ECGs (electrocardiograms) at least 5 minutes apart of ≥450 ms.
Congestive Heart Failure (NYHA Class III/IV) or LVEF (left ventricular ejection fraction) <50% at baseline.
Uncontrolled hypertension (HTN) despite medical management (blood pressure (BP) ≥ 160/100.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pazopanib	Low Fat Diet	Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) approximately, some sample meals are described in appendix 1) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.
Pazopanib	Pazopanib	Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) approximately, some sample meals are described in appendix 1) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Primary Outcome Measures

Name	Time	Method
Median Total Dose	12 weeks	Median total dose given.
Duration of Treatment	12 weeks	The median duration of treatment will be reported.
Number of Grade 3 or 4 Adverse Events	Through 12 weeks of treatment to 30 days post-treatment	Number of grade 3 or 4 adverse events associated with pazopanib administered with a low fat meal by CTCAE version 4.0.
Number of Participants With Dose Reductions	12 weeks

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Partial Response	12 Weeks after start of study treatment	Partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Percentage of Patients That Respond to Treatment (Overall Response) With Pazopanib Administered Along With a Low Fat Diet	12 Weeks after start of study treatment	To estimate the overall response proportion to pazopanib administered with a low fat meal by RECIST 1.1 criteria. Overall response is defined as the number patients that experience Partial Response (PR) or Complete Response (CR). CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. PR is defined as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Number of Participants With Complete Response	12 Weeks after start of study treatment	Complete response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.