Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment

NCT01853046 | Completed Phase 1 Results

• 1 other identifier: 16653
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 9

Brief Summary

To characterize the pharmacokinetics and safety of regorafenib in cancer subjects with severe renal impairment when compared to the Control group (cancer subjects with normal or mildly impaired renal function)

Conditions

Neoplasms

Keywords

Regorafenib; pharmacokinetics; safety; severe renal impairment; Solid tumors

Outcome Measures

Primary Outcomes (2)

• AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5

  Based on non-compartmental PK evaluation. The AUC(0-tlast) \[Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point \>LLOQ (Lower Limit of Quantification)\] is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.

  Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose

• AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0-24 Hours Post Administration) for Metabolites M-7 and M-8

  Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose.

  Days 1-2: 0-24 hours

Secondary Outcomes (21)

• AUC (Area Under the Plasma Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5

  Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose

• AUC(0-24) (AUC From Time Zero to 24 Hours p.a. After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5

  Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose

• Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5

  Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose

• Tmax (Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5

  Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose

• Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5

  Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose

Other Outcomes (1)

• Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)

  Up to 6 months

Study Arms (2)

Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment

EXPERIMENTAL

Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.

Drug: Regorafenib (Stivarga, BAY73-4506)

Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment

EXPERIMENTAL

Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.

Drug: Regorafenib (Stivarga, BAY73-4506)

Interventions

Regorafenib (Stivarga, BAY73-4506) DRUG

Regorafenib 160 mg o.d. will be administered as a single dose on Day 1 of Stage 1 followed by multiple dosing in an intermittent administration schedule (3 week-on/1 week-off) over 2 cycles in Stage 2 (56 days, cycle defined as 28 days)

Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment; Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapy
• Male or female subject ≥ 18 years of age
• Women of childbearing potential must have a negative urine pregnancy test performed within 7 days before start of study treatment
• Life expectancy at least 8 weeks
• Adequate bone marrow, and liver function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• For subjects with NORMAL OR MILDLY IMPAIRED RENAL FUNCTION (Control group); to be tested within 7 days of starting the study treatment:
• Estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using the Cockcroft-Gault equation
• For subjects with SEVERELY IMPAIRED renal function; to be tested within 7 days of starting the study treatment:
• CLcr 15-29 mL/min as calculated using the Cockcroft-Gault equation

You may not qualify if:

• Symptomatic metastatic brain or meningeal tumors
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
• History of organ allograft
• Non-healing wound, skin ulcer, or bone fracture
• Pheochromocytoma
• Uncontrolled concurrent medical illness including uncontrolled hypertension
• History of cardiac disease
• Pleural effusion or ascites that causes respiratory compromise
• Interstitial lung disease with ongoing signs and symptoms at the time of screening
• 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 NCI-CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment
• Dehydration NCI-CTCAEversion 4.0 Grade ≥ 1
• Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 attributed to any prior therapy/procedure (excluding alopecia or anemia or grade 2 neuropathy that is not reversible due to oxaliplatin)
• Seizure disorder requiring anticonvulsant therapy (such as steroids or anti-epileptics)
• For subjects with SEVERELY IMPAIRED renal function:

Sponsors & Collaborators

• Bayer: lead

Study Sites (9)

Unknown Facility

Los Angeles, California, 90033, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Lebanon, New Hampshire, 03756, United States

Location

Unknown Facility

Buffalo, New York, 14263-0001, United States

Location

Unknown Facility

Edmonton, Alberta, T6G 1Z2, Canada

Location

Unknown Facility

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Unknown Facility

Hamilton, Ontario, L8V 5C2, Canada

Location

Unknown Facility

Montreal, Quebec, H2L 4M1, Canada

Location

MeSH Terms

Conditions

Neoplasms; Renal Insufficiency

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2013
• First Posted: May 14, 2013
• Study Start: June 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 20, 2017
• Results First Posted: February 20, 2017

Record last verified: 2016-12

Locations

CA (4); US (5)