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

March 8, 2019 updated by: University of Michigan Rogel Cancer Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: Pazopanib
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Grade 3 or 4 Adverse Events
Time Frame: 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.
Through 12 weeks of treatment to 30 days post-treatment
Number of Participants With Dose Reductions
Time Frame: 12 weeks
12 weeks
Duration of Treatment
Time Frame: 12 weeks
The median duration of treatment will be reported.
12 weeks
Median Total Dose
Time Frame: 12 weeks
Median total dose given.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients That Respond to Treatment (Overall Response) With Pazopanib Administered Along With a Low Fat Diet
Time Frame: 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.
12 Weeks after start of study treatment
Number of Participants With Complete Response
Time Frame: 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.
12 Weeks after start of study treatment
Number of Patients With Partial Response
Time Frame: 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.
12 Weeks after start of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan Rogel Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (ACTUAL)

September 1, 2017

Study Completion (ACTUAL)

September 1, 2017

Study Registration Dates

First Submitted

March 22, 2016

First Submitted That Met QC Criteria

April 5, 2016

First Posted (ESTIMATE)

April 6, 2016

Study Record Updates

Last Update Posted (ACTUAL)

June 10, 2019

Last Update Submitted That Met QC Criteria

March 8, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCC 2016.013
  • HUM00111682 (OTHER: University of Michigan)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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