Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma
2 other identifiers
interventional
16
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for early_phase_1
Started Jun 2016
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 22, 2016
CompletedFirst Posted
Study publicly available on registry
April 6, 2016
CompletedStudy Start
First participant enrolled
June 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2017
CompletedResults Posted
Study results publicly available
June 10, 2019
CompletedJune 10, 2019
March 1, 2019
1.3 years
March 22, 2016
September 18, 2018
March 8, 2019
Conditions
Outcome Measures
Primary Outcomes (4)
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.
Through 12 weeks of treatment to 30 days post-treatment
Number of Participants With Dose Reductions
12 weeks
Duration of Treatment
The median duration of treatment will be reported.
12 weeks
Median Total Dose
Median total dose given.
12 weeks
Secondary Outcomes (3)
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
Number of Participants With Complete Response
12 Weeks after start of study treatment
Number of Patients With Partial Response
12 Weeks after start of study treatment
Study Arms (1)
Pazopanib
EXPERIMENTALRegistered 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Related Publications (1)
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.
PMID: 30393825DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Ajjai Alva, M.D.
- Organization
- University of Michigan Rogel Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Ajjai Alva, M.D.
University of Michigan Rogel Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 22, 2016
First Posted
April 6, 2016
Study Start
June 1, 2016
Primary Completion
September 1, 2017
Study Completion
September 1, 2017
Last Updated
June 10, 2019
Results First Posted
June 10, 2019
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will not share