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Metastatic Solid MalignanciesPhase 1NCT02439723

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

A Phase 1 study testing Regorafenib in people with Metastatic Solid Malignancies and Locally Advanced Solid Malignancies, run by AHS Cancer Control Alberta at 1 site in Canada.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteCanada
Study dates
Mar 2016to Dec 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Adequate bone marrow, and liver function as assessed by the designated laboratory levels within 7 days of starting study treatment:
  • Platelet count ≥ 100,000/cubic millimeters, hemoglobin (Hb) ≥ 8.0 g/dl, absolute neutrophil count (ANC) ≥ 1500 cubic millimeters
  • 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
  • Alanine aminotransferase (ALT) and asparate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN for subjects whose cancer involves their liver including liver metastasis).
  • Alkaline phosphatase limit ≤ 2.5 times ULN (≤ 5 ULN for subjects whose cancer involves their liver including liver metastasis)
  • Amylase and lipase ≤ 1.5 times ULN
  • International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) ≤ 1.5 times ULN. Subjects who are being treated with heparin or warfarin are allowed to participate.
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute as calculated using the Cockcroft-Gault formula

Who cannot join

  • 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
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  • 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.
  • Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding event CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment.
  • Dehydration CTCAE Grade ≥1
  • Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 (excluding alopecia, anemia or lymphopenia) attributed to any prior systemic or radiation therapy or other medical or surgical procedure
  • Known hypersensitivity to regorafenib, study drug class, or excipients in the formulation.
  • Ongoing or active infection (bacterial, fungal or viral, e.g. human immunodeficiency virus (HIV)) of NCI-CTCAE version 4.0 Grade ≥ 2
  • Seizure disorder requiring anti-convulsant therapy (such as steroids or anti-epileptics)
  • Pregnancy and lactation (breastfeeding)
  • During the study, no other anticancer treatment, including any investigational new drugs, is allowed. Anticancer therapy is defined as any agent or combination of agents with clinically proven anticancer activity. Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy and hormonal therapy during this trial or within 28 days or 5 drug half lives (if drug half-life in subject is known), whichever is shorter (or within 6 weeks or mitomycin C) before start of the study treatment
  • Use of hematopoietic growth factors, such as G-CSF (granulocyte colony-stimulating factor), GM-CSF (granulocyte-macrophage colony-stimulating factor), erythropoietin, and interleukin (IL-2, IL-3), within 3 weeks prior to first dose. Subjects taking chronic erythropoietin consistent with institutional guidelines can be included.
  • Close affiliation with the investigational site; e.g. a close relative of the investigator or a dependent person (e.g. employee or student of the investigational site)
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • Inability to swallow oral medications.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

Other trials in Canada

About this study

Official title: 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

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.

Read the 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.

Being tested
Regorafenib
Keywords
Regorafenib, Lean body mass, Proton pump inhibitors pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02439723
Study groupRoleWhat they receive
RegorafenibExperimentalAll patients will be treated with 160 mg regorafenib taken orally once daily for the first 21 days of each 28-day cycle. Doses are to be taken immediately following a light breakfast. During the seven-day break period of cycle 1, patients will start pantoprazole 40 mg twice daily for 8 days
Receives: Drug: Regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Peak plasma concentration of regorafenib

    Peak plasma concentrations of regorafenib, M-2 and M-5 after single-dose and multiple-dose administration. The outcome will be measured during cycles 1 and 2 using pharmacokinetic blood samples collected on

    Measured: 5 days

Secondary outcomes (1)

  1. The area under the concentration-time curve (AUC) for regorafenib

    The outcome will be measured during cycles 1 and 2 using pharmacokinetic blood samples collected on days 1, 2, 3 and 5 of both cycles

    Measured: 5 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2015 (estimated)
  2. Study startMar 2016 (estimated)
  3. Primary completionJun 2017 (estimated)
  4. Study completionDec 2017 (estimated)

Why it stopped: Withdrawal of supply of investigational product

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02439723
Sponsor's protocol ID
Regorafenib 1.0
Status last verified
Jun 2021
First submitted
7 May 2015
Last updated
23 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Regorafenib in people with Metastatic Solid Malignancies and Locally Advanced Solid Malignancies, run by AHS Cancer Control Alberta at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 23 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak plasma concentration of regorafenib (time frame: 5 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02439723.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2021.

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