Sorafenib Study: Dosing in Patients With Pulmonary Arterial Hypertension (PAH)

NCT00452218 | Completed Phase 1 DMC

• 1 other identifier: 14636A
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and tolerability of sorafenib in patients with PAH already on existing therapy with a prostacyclin \[epoprostenol (Flolan)\], treprostinil (Remodulin), or iloprost alone, or with or without sildenafil (Viagra/Revatio).

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; PAH

Outcome Measures

Primary Outcomes (1)

• Monthly 6MW/B

  16 weeks

Secondary Outcomes (4)

• Efficacy

  16 Weeks

• World Health Organization (WHO) function class

  16 weeks

• Right heart catheterization

  16 Week

• Naughton Balke-Treadmill Test

  16 Weeks

Study Arms (1)

Open

EXPERIMENTAL

Drug: Sorafenib

Interventions

Sorafenib DRUG

200 mg daily and dose escalated to a maximum of 400 mg twice daily

Also known as: BAY 43-9006, Nexavar

Open

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• PAH defined as IPAH, FPAH, or PAH associated with collagen vascular disease
• Baseline 6MW \> 150 meters
• PAH as defined by hemodynamics at diagnosis by right heart catheterization defined as: mean PAP \> 25 mmHg with a normal PCWP \< 15 mm Hg at rest and a PVR \> 3 Wood units
• Receiving conventional therapy as clinically indicated (oxygen, diuretics, aldosterone antagonist, calcium channel blockers, digoxin) with dose that is unchanged in the preceding 30 days prior to enrollment. This is excluding anticoagulants (warfarin) as the patient's dose may not be stable if the patient is having a cardiac catheterization at baseline within 30 days of enrollment and warfarin is being held. The dose of warfarin needs to be stable for 7 days or therapeutic with an INR = 2.0
• If on intravenous/subcutaneous prostacyclin at a stable dose \> 30 days
• If subjects are on sildenafil, must be at a stable dose \> 30 days
• Must have right heart catheterization on prostacyclin + sildenafil within preceding 30 days. Subjects must be on a stable dose of medication within 30 days prior to cardiac catheterization and therefore there can be no dosage changes of the medications between catheterization and baseline
• Must have pulmonary function tests (PFT) within 90 days prior to enrollment: TLC, FEV1, FVC, DLCO
• Women of childbearing years must use adequate contraception (hormonal or barrier method of birth control) prior to enrollment. Subjects need to have a negative serum or urine pregnancy test.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• PAH associated with all other etiologies: HIV, portopulmonary disease, congenital heart disease
• Subjects with pulmonary hypertension due to thromboembolism, significant interstitial lung disease, chronic obstructive pulmonary disease, congestive heart failure, valvular heart disease
• Subjects with (World Health Organization (WHO) functional Class IV(19)
• Subjects with scleroderma with total lung capacity (TLC) \< 60% of predicted within 30 days of screening
• Subjects with significant obstructive lung disease with FEV1/FVC \< 80% of predicted
• Subjects with hypotension defined as systolic arterial pressure \< 90 mmHg at baseline
• Subjects with hypertension defined as systolic arterial pressure \>140 mmHg at baseline or a diastolic arterial pressure \> 90 mmHg
• Subjects with impaired renal function defined as creatinine clearance \< 30 ml/min as defined by the Cockcroft-Gault formula:
• Male: creatinine clearance (ml/min) = (140-age) x (body weight in kg)/ (72x serum creatinine in mg/dl);
• Female: creatinine clearance (ml/min)= 0.85 (140-age) x (body weight in kg)/ (72x serum creatinine in mg/dl)
• Subjects with liver function tests (transaminases (AST/ALT), total bilirubin, and alkaline phosphatase) \> 2X normal values
• Subjects with acutely decompensated heart failure or hospitalization within the previous 30 days prior to screening
• Subjects may not be receiving any other investigational agents
• Subjects on endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan) or chronic arginine supplementation
• Subjects with left ventricular ejection fraction \< 45% or left ventricular shortening fraction \< 0.2

Sponsors & Collaborators

• University of Chicago: lead
• Bayer: collaborator

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mardi Gomberg, M.D.

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 26, 2007
• First Posted: March 27, 2007
• Study Start: March 1, 2007
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: August 24, 2016

Record last verified: 2016-08

Locations

US (1)