Renal Cell CarcinomaPhase 2HYPAZNCT01392352
HYPAZ: Hypertension Induced by Pazopanib
A Phase 2 study testing Pazopanib in people with Renal Cell Carcinoma and Soft Tissue Sarcoma, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Pazopanib is a new cancer drug that works by limiting the growth of new blood vessels in tumours. About half of patients who take pazopanib develop high blood pressure (hypertension). This side effect can make patients have to reduce or stop their cancer treatment, and can cause other health problems. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma, Soft Tissue Sarcoma, Glioblastoma
- What is being tested?
- Pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2011to Sep 2015
- Phase
- Phase 2
- 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
- Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.
- Patients with the following tumour types where VEGF inhibition would be appropriate therapy:
- a Renal cell carcinoma b Ovarian carcinoma with a rising CA-125, 2nd or subsequent lines c Ovarian carcinoma with residual disease after chemotherapy in the absence of rising CA-125, 2nd or subsequent lines d Cervical cancer, metastatic or recurrent, and progressing after conventional chemotherapy e Glioblastoma, progressing after conventional chemotherapy f Advanced or metastatic soft tissue sarcoma, residual disease post chemotherapy in the absence of progression, 2nd or subsequent lines g Advanced or metastatic soft tissue sarcoma progressing post conventional chemotherapy, 3rd or subsequent lines h Non-small cell lung cancer, 1st or subsequent lines i ErbB2 positive, advanced or metastatic breast cancer, 2nd or subsequent lines j Gemcitabine-refractory pancreatic cancer, 2nd or subsequent lines k Non-cutaneous (ocular or mucosal) melanoma and cutaneous melanoma any line l GI tract 2nd line residual disease or subsequent lines m Small Cell Lung cancer 3rd line n Other solid tumours in which anti-VEGF therapy is judged by the CI to be of possible clinical benefit
- Measurable disease as per RECIST 1.1. A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques. Patients with ovarian cancer or prostate cancer, where validated tumour markers (CA125 and PSA) are used clinically to monitor response, do not require measurable disease as per RECIST 1.1.
- ECOG performance status 0 or 1.
- Age ≥18 years.
- Adequate organ system function
- Female participant, or female partner of male participant, are of non-childbearing potential or agree to protocol-specified contraceptive measures
Who cannot join
- Known hypertension (blood pressure >150/90 mmHg (± 2 mmHg, at investigator's discretion) at baseline
- On anti-hypertensive therapy indicated for hypertension
- History of any one or more of the following cardiovascular conditions within the last 6 months:
- a Cardiac angioplasty or stenting b Myocardial infarction c Unstable angina d Coronary artery bypass graft surgery e Peripheral vascular disease or Raynaud's phenomenon f Cerebrovascular accident (CVA) including transient ischaemic attack (TIA), g Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- Hypersensitivity to agents used in forearm blood flow studies (acetylcholine, sodium nitroprusside, L-NMMA)
- Difficult upper limb arterial access (as assessed by an easily palpable brachial artery)
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- Anticoagulant therapy (warfarin). (Subcutaneous heparin is allowed but will need to be omitted on visits V2, V3 and VHyp).
- Pregnant or lactating female
- History or clinical evidence of active central nervous system (CNS) metastases.
- Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- Presence of uncontrolled infection
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula
- History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
- Prior major surgery or trauma within 28 days prior to first dose and/or presence of any non-healing wound, fracture, or ulcer.
- Evidence of active bleeding or bleeding diathesis
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
- Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumour that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
- Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.
- Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.
- Significant haemoptysis within 8 weeks prior to first dose of pazopanib (≥½ teaspoon of red blood within 8 weeks before first dose of study drug).
- Any serious and/or pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures.
- Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib and for the duration of the study.
- Treatment with any of the following anti-cancer therapies:
- a radiation therapy (single fraction radiotherapy for pain control is allowed in this period and when on study), surgery or tumour embolization within 14 days prior to the first dose of pazopanib OR b chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib c pazopanib or other antiangiogenic treatment (e.g. bevacizumab) within the past 12 weeks.
- Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment.
- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: HYPAZ: An Open-label Investigation Into Hypertension Induced by Pazopanib Therapy
Pazopanib is a new cancer drug that works by limiting the growth of new blood vessels in tumours. About half of patients who take pazopanib develop high blood pressure (hypertension). This side effect can make patients have to reduce or stop their cancer treatment, and can cause other health problems. The aim of this study is to find out exactly how the drug causes high blood pressure.
Read the detailed description
For this study, up to 52 patients with different cancer types will take pazopanib tablets for 12 weeks. They will visit the clinic every 1-2 weeks during treatment, and for a final safety check 4 weeks after stopping the drug (10 visits over 18 weeks).
At every visit, we will do a heart tracing, and check the patient's blood pressure and blood and urine chemicals (to check their health, and see if levels of these chemicals change). Patients will check their blood pressure at home every other day. They will also wear a blood pressure monitor for 24 hours on 3 occasions (during normal daily activities).
Patients will have 1 or 2 CT scans and 3 MRI scans during the study. On three occasions, a variety of specialised tests will measure how the patient's blood vessels are working.
Patients may choose to continue taking the drug after the 12 weeks of treatment, if their doctor feels it is appropriate.
Understanding how pazopanib causes high blood pressure will help us to advise doctors how to treat the high blood pressure effectively, so that patients can continue to take their cancer treatment safely. This research might also lead to the development of new cancer drugs in future, which do not cause this serious side effect.
- Conditions
- Renal Cell Carcinoma, Soft Tissue Sarcoma, Glioblastoma, Ovarian Cancer, Cervical Cancer, Breast Cancer
- Being tested
- Pazopanib
- Keywords
- pazopanib, hypertension, forearm blood flow
- Medical subject headings
- Carcinoma, Renal Cell, Sarcoma, Glioblastoma, Ovarian Neoplasms, Uterine Cervical Neoplasms, Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Also called Votrient
2 x 400mg pazopanib tablets taken once daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib | Experimental | Patients will receive 800mg (2 X 400mg tablets) of pazopanib, to be administered once daily orally for 12 weeks or until development of hypertension (defined as VHyp), whichever occurs first. Receives: Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in endothelial dependent function
Measured: Measured over 12 weeks, or at the onset of hypertension whichever occurs first
Secondary outcomes (1)
Change in endothelial independent function
Measured: Measured over 12 weeks, or at onset of hypertension, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2011 (estimated)
- Study startApr 2011
- Primary completionSep 2014
- Study completionSep 2015
Why it stopped: Following DMC review, due to slow recruitment of evaluable patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cambridge
- Responsible party
- Principal investigator, Duncan Jodrell, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Duncan I Jodrell, Principal investigator, University of Cambridge; honorary contract with Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01392352
- Sponsor's protocol ID
- A091962
- Other IDs
- 2010-021613-23
- Acronym
- HYPAZ
- Status last verified
- Feb 2020
- First submitted
- 30 Jun 2011
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Maki-Petaja KM, McGeoch A, Yang LL, Hubsch A, McEniery CM, Meyer PAR, Mir F, Gajendragadkar P, Ramenatte N, Anandappa G, Santos Franco S, Bond SJ, Schonlieb CB, Boink Y, Brune C, Wilkinson IB, Jodrell DI, Cheriyan J. Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial. Hypertension. 2021 May 5;77(5):1591-1599. doi: 10.1161/HYPERTENSIONAHA.120.16454. Epub 2021 Mar 29.
PubMed 33775123
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HYPAZ: An Open-label Investigation Into Hypertension Induced by Pazopanib Therapy
- ClinicalTrials.gov ID
- NCT01392352
- Acronym / sponsor ID
- HYPAZ / A091962
- Conditions
- Renal Cell Carcinoma, Soft Tissue Sarcoma, Glioblastoma, Ovarian Cancer, Cervical Cancer, Breast Cancer
- Keywords
- pazopanib, hypertension, forearm blood flow
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Following DMC review, due to slow recruitment of evaluable patients.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Cambridge
- Study start
- Apr 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 12 Jul 2011 (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.
Pazopanib is a new cancer drug that works by limiting the growth of new blood vessels in tumours. About half of patients who take pazopanib develop high blood pressure (hypertension). This side effect can make patients have to reduce or stop their cancer treatment, and can cause other health problems. The aim of this study is to find out exactly how the drug causes high blood pressure.
Detailed description
For this study, up to 52 patients with different cancer types will take pazopanib tablets for 12 weeks. They will visit the clinic every 1-2 weeks during treatment, and for a final safety check 4 weeks after stopping the drug (10 visits over 18 weeks).
At every visit, we will do a heart tracing, and check the patient's blood pressure and blood and urine chemicals (to check their health, and see if levels of these chemicals change). Patients will check their blood pressure at home every other day. They will also wear a blood pressure monitor for 24 hours on 3 occasions (during normal daily activities).
Patients will have 1 or 2 CT scans and 3 MRI scans during the study. On three occasions, a variety of specialised tests will measure how the patient's blood vessels are working.
Patients may choose to continue taking the drug after the 12 weeks of treatment, if their doctor feels it is appropriate.
Understanding how pazopanib causes high blood pressure will help us to advise doctors how to treat the high blood pressure effectively, so that patients can continue to take their cancer treatment safely. This research might also lead to the development of new cancer drugs in future, which do not cause this serious side effect.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pazopanib | Experimental | Drug: PazopanibPatients will receive 800mg (2 X 400mg tablets) of pazopanib, to be administered once daily orally for 12 weeks or until development of hypertension (defined as VHyp), whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.
- Patients with the following tumour types where VEGF inhibition would be appropriate therapy:
- a Renal cell carcinoma b Ovarian carcinoma with a rising CA-125, 2nd or subsequent lines c Ovarian carcinoma with residual disease after chemotherapy in the absence of rising CA-125, 2nd or subsequent lines d Cervical cancer, metastatic or recurrent, and progressing after conventional chemotherapy e Glioblastoma, progressing after conventional chemotherapy f Advanced or metastatic soft tissue sarcoma, residual disease post chemotherapy in the absence of progression, 2nd or subsequent lines g Advanced or metastatic soft tissue sarcoma progressing post conventional chemotherapy, 3rd or subsequent lines h Non-small cell lung cancer, 1st or subsequent lines i ErbB2 positive, advanced or metastatic breast cancer, 2nd or subsequent lines j Gemcitabine-refractory pancreatic cancer, 2nd or subsequent lines k Non-cutaneous (ocular or mucosal) melanoma and cutaneous melanoma any line l GI tract 2nd line residual disease or subsequent lines m Small Cell Lung cancer 3rd line n Other solid tumours in which anti-VEGF therapy is judged by the CI to be of possible clinical benefit
- Measurable disease as per RECIST 1.1. A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques. Patients with ovarian cancer or prostate cancer, where validated tumour markers (CA125 and PSA) are used clinically to monitor response, do not require measurable disease as per RECIST 1.1.
- ECOG performance status 0 or 1.
Key exclusion criteria (28 listed)
- Known hypertension (blood pressure >150/90 mmHg (± 2 mmHg, at investigator's discretion) at baseline
- On anti-hypertensive therapy indicated for hypertension
- History of any one or more of the following cardiovascular conditions within the last 6 months:
- a Cardiac angioplasty or stenting b Myocardial infarction c Unstable angina d Coronary artery bypass graft surgery e Peripheral vascular disease or Raynaud's phenomenon f Cerebrovascular accident (CVA) including transient ischaemic attack (TIA), g Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- Hypersensitivity to agents used in forearm blood flow studies (acetylcholine, sodium nitroprusside, L-NMMA)
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 |
|---|---|---|
| PazopanibAlso: Votrient2 x 400mg pazopanib tablets taken once daily for 12 weeks | Drug | Pazopanib |
Primary outcome
Change in endothelial dependent function
Time frame: Measured over 12 weeks, or at the onset of hypertension whichever occurs first
1 secondary outcome
Change in endothelial independent function
Time frame: Measured over 12 weeks, or at onset of hypertension, whichever occurs first
Results and safety
The study was stopped early (reason given: Following DMC review, due to slow recruitment of evaluable patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Derived from this study: PubMed 33775123Maki-Petaja KM, McGeoch A, Yang LL, Hubsch A, McEniery CM, Meyer PAR, Mir F, Gajendragadkar P, Ramenatte N, Anandappa G, Santos Franco S, Bond SJ, Schonlieb CB, Boink Y, Brune C, Wilkinson IB, Jodrell DI, Cheriyan J. Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial. Hypertension. 2021 May 5;77(5):1591-1599. doi: 10.1161/HYPERTENSIONAHA.120.16454. Epub 2021 Mar 29.
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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.
Duncan I Jodrell principal investigator
University of Cambridge; honorary contract with Cambridge University Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pazopanib in people with Renal Cell Carcinoma and Soft Tissue Sarcoma, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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 8 inclusion and 28 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: stopped early, as of the sponsor's last update on 13 Feb 2020. 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 Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 stopped early (reason given: Following DMC review, due to slow recruitment of evaluable patients.). Results are not available in the source record.
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?
Change in endothelial dependent function (time frame: Measured over 12 weeks, or at the onset of hypertension whichever occurs first). 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 NCT01392352, which also lists 1 linked publication.
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 13 Feb 2020.