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HYPAZ: An Open-label Investigation Into Hypertension Induced by Pazopanib Therapy

Phase 2
18 Years
Open (Enrolling)
Renal Cell Carcinoma, Soft Tissue Sarcoma, Glioblastoma, Ovarian Cancer, Cervical Cancer, Breast Cancer, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Pancreatic Cancer, Melanoma, Gastrointestinal Cancer

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Trial Information

HYPAZ: An Open-label Investigation Into Hypertension Induced by Pazopanib Therapy

For this study, up to 52 patients with different cancer types will take pazopanib tablets
for 12 weeks. They will visit the clinic every 2 weeks during treatment, and for a final
safety check 4 weeks after stopping the drug (9 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.

Inclusion Criteria:

1. 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

2. Patients with the following tumour types where VEGF inhibition would be appropriate

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
Non-small cell lung cancer, 1st or subsequent lines h ErbB2 positive, advanced or
metastatic breast cancer, 2nd or subsequent lines i Gemcitabine-refractory pancreatic
cancer, 2nd or subsequent lines j Non-cutaneous (ocular or mucosal) melanoma and
cutaneous melanoma any line k GI tract 2nd line residual disease or subsequent lines
l Small Cell Lung cancer 3rd line m Other solid tumours in which anti-VEGF
therapy is judged by the CI to be of possible clinical benefit

3. 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.

4. ECOG performance status 0 or 1.

5. Age ≥18 years.

6. Adequate organ system function

7. Female participant, or female partner of male participant, are of non-childbearing
potential or agree to protocol-specified contraceptive measures

Exclusion Criteria:

1. Known hypertension (blood pressure >150/90 mmHg(± 2 mmHg, at investigator's
discretion) at baseline

2. On anti-hypertensive therapy indicated for hypertension

3. 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)

4. Hypersensitivity to agents used in forearm blood flow studies (acetylcholine, sodium
nitroprusside, L-NMMA)

5. Difficult upper limb arterial access (as assessed by an easily palpable brachial

6. Anticoagulant therapy (warfarin)(Subcutaneous heparin is allowed but will need to be
omitted on visits V2, V3 and VHyp).

7. Pregnant or lactating female

8. History or clinical evidence of active central nervous system (CNS) metastases.

9. Clinically significant gastrointestinal abnormalities that may increase the risk for
GI bleeding

10. Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product

11. Presence of uncontrolled infection

12. Corrected QT interval (QTc) > 480 msecs using Bazett's formula

13. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the
past 6 months

14. Prior major surgery or trauma within 28 days prior to first dose and/or presence of
any non-healing wound, fracture, or ulcer.

15. Evidence of active bleeding or bleeding diathesis

16. 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).

i) Large protruding endobronchial lesions in the main or lobar bronchi are excluded;
however, endobronchial lesions in the segmented bronchi are allowed.

ii) 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).

17. 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.

18. 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.

19. 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.

20. 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.

21. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia.

22. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Outcome Measure:

Change in endothelial dependent function

Outcome Time Frame:

Measured over 12 weeks, or at the onset of hypertension whichever occurs first

Safety Issue:



United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

April 2011

Completion Date:

September 2018

Related Keywords:

  • Renal Cell Carcinoma
  • Soft Tissue Sarcoma
  • Glioblastoma
  • Ovarian Cancer
  • Cervical Cancer
  • Breast Cancer
  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Pancreatic Cancer
  • Melanoma
  • Gastrointestinal Cancer
  • pazopanib
  • hypertension
  • forearm blood flow
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell
  • Uterine Cervical Neoplasms
  • Glioblastoma
  • Hypertension
  • Lung Neoplasms
  • Melanoma
  • Ovarian Neoplasms
  • Pancreatic Neoplasms
  • Small Cell Lung Carcinoma
  • Gastrointestinal Neoplasms
  • Sarcoma