Pulmonary Arterial HypertensionPhase 1NCT00452218
Sorafenib Study: Dosing in Patients With Pulmonary Arterial Hypertension (PAH)
A Phase 1 study testing Sorafenib in people with Pulmonary Arterial Hypertension, run by University of Chicago at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Sorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to May 2012
- 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
- 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
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- 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
Who cannot join
- 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
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- 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
- Subjects with acute myocardial infarction within 90 days prior to screening
- Subjects with limitations to performance of exercise measures (6MW) due to conditions other than PH associated dyspnea/fatigue
- Subjects taking nitrates for any medical problem
- Subjects taking phosphodiesterase inhibitors (any formulation) for erectile dysfunction
- Subjects with a recent (< 180 days) history of pulmonary embolism verified by ventilation/perfusion scan, angiogram, or spiral CT scan
- Pregnant or lactating women
- Subjects with a history of current drug abuse including alcohol
Trial locations and contacts
1 site in 1 country.
About this study
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).
Read the detailed description
Pulmonary arterial hypertension (PAH) is an angioproliferative vasculopathy resulting from abnormal endothelial and smooth muscle cell interactions. Idiopathic and familial PAH (formerly known as primary pulmonary hypertension) occurs more often in women than in men, with a median survival of 2.8 years if untreated and a mean age at diagnosis of 35 years. The key features of this vasculopathy causes a progressive narrowing of the pulmonary artery and their branches, resulting in right heart failure and death. Proliferating endothelial cells obliterate medium-sized precapillary arteries, thereby forming the characteristic "plexiform" lesions. When combined with the expansion of both vascular smooth muscle cells and adventitial cells in pulmonary arteries, these observations evoke comparisons to cancer pathobiology. Currently, FDA-approved therapies for PAH such as prostacyclins (epoprostenol, treprostinil, and iloprost), endothelin receptor blockers (bosentan) and phosphodiesterase inhibitors (sildenafil) all produce functional improvement (6 minute walk distance- 6MW) with minimal change in hemodynamic measurements at cardiac catheterization. Only epoprostenol has provided survival benefit with the 5-year survival, remaining at 50% without demonstrable reversal of the vasculopathy. Clearly there is a critical need for novel targets and therapies for PAH.
In this protocol, the principal investigator (PI) will leverage a large PAH referral practice with an established clinical database to assess the potential utility of kinase inhibitors as a new class of agents for protease-activated receptor (PAR). These drugs inhibit processes important to pathological blood vessel branching and growth and have been a focus for the internationally renowned University of Chicago Phase I/II trials unit in oncology led by Dr. Mark Ratain (Co-Investigator). The University of Chicago has had a major role in the drug development of the recently (12/05) FDA-approved drug, sorafenib, for advanced renal carcinoma. Sorafenib inhibits Raf-1 kinase, a regulator of endothelial apoptosis, and inhibits angiogenesis growth factor receptors VEGFR-2, PDGFR-B, and VEGFR-3.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Sorafenib
- Keywords
- Pulmonary Arterial Hypertension, PAH
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called BAY 43-9006, Nexavar
200 mg daily and dose escalated to a maximum of 400 mg twice daily
| Study group | Role | What they receive |
|---|---|---|
| Open | Experimental | Not described Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monthly 6MW/B
Measured: 16 weeks
Secondary outcomes (4)
Efficacy
Measured: 16 Weeks
World Health Organization (WHO) function class
Measured: 16 weeks
Right heart catheterization
Measured: 16 Week
Naughton Balke-Treadmill Test
Measured: 16 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2007 (estimated)
- Study startMar 2007
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Mardi Gomberg, M.D., Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00452218
- Sponsor's protocol ID
- 14636A
- Status last verified
- Aug 2016
- First submitted
- 26 Mar 2007
- Last updated
- 24 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sorafenib Study: Dosing in Patients With Pulmonary Arterial Hypertension (PAH)
- ClinicalTrials.gov ID
- NCT00452218
- Acronym / sponsor ID
- 14636A
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, PAH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Mar 2007
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 27 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Pulmonary arterial hypertension (PAH) is an angioproliferative vasculopathy resulting from abnormal endothelial and smooth muscle cell interactions. Idiopathic and familial PAH (formerly known as primary pulmonary hypertension) occurs more often in women than in men, with a median survival of 2.8 years if untreated and a mean age at diagnosis of 35 years. The key features of this vasculopathy causes a progressive narrowing of the pulmonary artery and their branches, resulting in right heart failure and death. Proliferating endothelial cells obliterate medium-sized precapillary arteries, thereby forming the characteristic "plexiform" lesions. When combined with the expansion of both vascular smooth muscle cells and adventitial cells in pulmonary arteries, these observations evoke comparisons to cancer pathobiology. Currently, FDA-approved therapies for PAH such as prostacyclins (epoprostenol, treprostinil, and iloprost), endothelin receptor blockers (bosentan) and phosphodiesterase inhibitors (sildenafil) all produce functional improvement (6 minute walk distance- 6MW) with minimal change in hemodynamic measurements at cardiac catheterization. Only epoprostenol has provided survival benefit with the 5-year survival, remaining at 50% without demonstrable reversal of the vasculopathy. Clearly there is a critical need for novel targets and therapies for PAH.
In this protocol, the principal investigator (PI) will leverage a large PAH referral practice with an established clinical database to assess the potential utility of kinase inhibitors as a new class of agents for protease-activated receptor (PAR). These drugs inhibit processes important to pathological blood vessel branching and growth and have been a focus for the internationally renowned University of Chicago Phase I/II trials unit in oncology led by Dr. Mark Ratain (Co-Investigator). The University of Chicago has had a major role in the drug development of the recently (12/05) FDA-approved drug, sorafenib, for advanced renal carcinoma. Sorafenib inhibits Raf-1 kinase, a regulator of endothelial apoptosis, and inhibits angiogenesis growth factor receptors VEGFR-2, PDGFR-B, and VEGFR-3.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open | Experimental | Drug: Sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibAlso: BAY 43-9006, Nexavar200 mg daily and dose escalated to a maximum of 400 mg twice daily | Drug | Open |
Primary outcome
Monthly 6MW/B
Time frame: 16 weeks
4 secondary outcomes
Efficacy
Time frame: 16 Weeks
World Health Organization (WHO) function class
Time frame: 16 weeks
Right heart catheterization
Time frame: 16 Week
Naughton Balke-Treadmill Test
Time frame: 16 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mardi Gomberg, M.D. principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sorafenib in people with Pulmonary Arterial Hypertension, run by University of Chicago at 1 site in United States.
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 11 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: finished, as of the sponsor's last update on 24 Aug 2016. 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 United States. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Monthly 6MW/B (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Aug 2016.