Back to resultsPilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma
Primary Purpose
Carcinoma, Renal Cell
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pazopanib
Low Fat Diet
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Renal Cell
Eligibility Criteria
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.
Sites / Locations
- University of Michigan Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Grade 3 or 4 Adverse Events
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
Duration of Treatment
The median duration of treatment will be reported.
Median Total Dose
Median total dose given.
Secondary Outcome Measures
Percentage of Patients That Respond to Treatment (Overall Response) With Pazopanib Administered Along With a Low Fat Diet
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
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.
Number of Patients With Partial Response
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.
Full Information
NCT ID
NCT02729194
First Posted
March 22, 2016
Last Updated
March 8, 2019
Sponsor
University of Michigan Rogel Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT02729194
Brief Title
Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma
Official Title
Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
September 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Intervention Type
Other
Intervention Name(s)
Low Fat Diet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Grade 3 or 4 Adverse Events
Description
Number of grade 3 or 4 adverse events associated with pazopanib administered with a low fat meal by CTCAE version 4.0.
Time Frame
Through 12 weeks of treatment to 30 days post-treatment
Title
Number of Participants With Dose Reductions
Time Frame
12 weeks
Title
Duration of Treatment
Description
The median duration of treatment will be reported.
Time Frame
12 weeks
Title
Median Total Dose
Description
Median total dose given.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Percentage of Patients That Respond to Treatment (Overall Response) With Pazopanib Administered Along With a Low Fat Diet
Description
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.
Time Frame
12 Weeks after start of study treatment
Title
Number of Participants With Complete Response
Description
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.
Time Frame
12 Weeks after start of study treatment
Title
Number of Patients With Partial Response
Description
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.
Time Frame
12 Weeks after start of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajjai Alva, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30393825
Citation
Reimers MA, Shango MM, Daignault-Newton S, Dedinsky R, Karsies D, Kraft S, Riddle L, Felton JA, Wen B, Gersch C, Rae JM, Redman BG, Alva AS. Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma. Invest New Drugs. 2019 Apr;37(2):323-330. doi: 10.1007/s10637-018-0692-8. Epub 2018 Nov 5.
Results Reference
derived
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Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma
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