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Effects of LBM and PPIs on Pharmacokinetics and Safety of Regorafenib (BAY 73-4506) in Cancer Patients | Clinical Trials | Clareo Health

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Effects of LBM and PPIs on Pharmacokinetics and Safety of Regorafenib (BAY 73-4506) in Cancer Patients

A Phase I, Open Label Study of the Effects of Lean Body Mass (LBM) and Proton Pump Inhibitors (PPIs) on Pharmacokinetics and Safety of Regorafenib (BAY 73-4506) in Cancer Patients

NCT02439723•AHS Cancer Control Alberta

View on ClinicalTrials.gov

Summary

The FDA and Health Canada have approved regorafenib at a daily dose of 160mg for the treatment of metastatic colorectal cancer and gastrointestinal stromal cancer; however, the 160 mg dose is not well tolerated by patients, especially women. The purpose of this study is to determine if lean body mass and acidity in the intestinal tract impact how regorafenib is absorbed into the bloodstream and then broken down and removed from the body. This may explain the side effects experienced at the 160 mg dose, especially by women, and inform regorafenib dosing in the future.

Detailed Description

Numerous investigators have noted that the recommended flat dosing of regorafenib of 160 mg orally, once daily is not well tolerated by patients, especially women. The purpose of this study is to determine if there is a correlation between lean body mass and regorafenib pharmacokinetics and if so, then it may be possible to exploit this relationship to better dose regorafenib. Additionally, Bayer has noted that regorafenib steady state levels were lower in gastrointestinal stromal tumour (GIST) patients than in patients with metastatic colorectal cancer. GIST patients have often had gastrectomies that would lead to an elevated pH in the intestinal tract. If regorafenib has a pH dependent solubility then lower regorafenib levels could be due to reduced acidity. The purpose of the second part of the study is to examine the regorafenib pharmacokinetic profile in patients treated with a proton pump inhibitor (pantoprazole) for 7 days, mimicking the altered intestinal environment seen in GIST patients.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Signed informed consent before any study procedures completed.
•Subjects with historically confirmed advanced metastatic or refractory solid malignancy who are not candidates for standard therapy.
•Male/female subjects ≥ 18 years of age
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
•Women of childbearing potential must have a negative urine pregnancy test performed within 7 days before starting study treatment. Women of childbearing potential and men must agree to use adequate contraception since the signing of informed consent until at least 8 weeks after the last study drug administration.
•Life expectancy of at least 8 weeks.
•Adequate bone marrow, and liver function as assessed by the designated laboratory levels within 7 days of starting study treatment:
•1. Platelet count ≥ 100,000/cubic millimeters, hemoglobin (Hb) ≥ 8.0 g/dl, absolute neutrophil count (ANC) ≥ 1500 cubic millimeters
•2. total bilirubin ≤ 1.5 times the upper limit of normal range (ULN). Mildly elevated total bilirubin (\<6 mg/dL) is allowed if Gilbert's syndrome is documented
•3. Alanine aminotransferase (ALT) and asparate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN for subjects whose cancer involves their liver including liver metastasis).
+4 more criteria

Exclusion Criteria

•Prior treatment with regorafenib. Patients permanently withdrawn from the study will not be allowed to re-enter the study
•Symptomatic metastatic brain or meningeal tumors unless the patient is greater than 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within four weeks prior to study entry and is not on dexamethasone and clinically stable with respect to the tumor at the time of surgery.
•Major surgery, open biopsy or significant traumatic injury within 28 days before starting the study treatment.
•History of organ allograft.
•Non-healing wound, skin ulcer or bone fracture.
•Uncontrolled intercurrent medical illness including uncontrolled hypertension defined as systolic blood pressure \> 150 millimeters of mercury (mmHg) or diastolic blood pressure \> 90 mmHg, despite medical management
•History of cardiac disease: congestive heart failure \> New York Heart Association (NYHA) Class II; unstable angina (symptoms of angina at rest), new-onset angina (within the last 3 months), myocardial infarction within the past 6 months prior to screening (Visit 1); cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (expect for beta-blockers and digoxin).
•Pleural effusion or ascites with causes respiratory compromise (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Grade ≥ 2 dyspnea).
•Interstitial lung disease with ongoing signs and symptoms within 28 days before starting the study treatment
•Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication.
+12 more criteria

Locations (1)

Cross Cancer Institute

Edmonton, Alberta, Canada

Key Dates

Start Date

March 1, 2016

Primary Completion Date

June 1, 2017

Completion Date

December 1, 2017

Last Updated

June 23, 2021

Conditions

Metastatic Solid MalignanciesLocally Advanced Solid Malignancies

Interventions

Regorafenib

DRUG

A Phase I Dose Escalation Study of Selinexor Plus Nivolumab and Ipilimumab in Advanced/Metastatic Solid Malignancies

NCT04850755

Advance Solid MalignanciesMetastatic Solid Malignancies

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: June 23, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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