HYPAZ: An open-label investigation into hypertension induced by pazopanib therapy - HYPAZ: Hypertension induced by pazopanib
- Conditions
- Hypertension induced by pazopanib treatment of various cancer typesMedDRA version: 16.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
- Registration Number
- EUCTR2010-021613-23-GB
- Lead Sponsor
- Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 27
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 up
2.Patients with the following tumour types where VEGF inhibition would be appropriate therapy will be included in the study:
• Renal cell carcinoma
• Ovarian carcinoma with a rising CA-125, 2nd or subsequent lines
• Ovarian carcinoma with residual disease after chemotherapy in the absence of rising CA-125, 2nd or subsequent lines
• Cervical cancer, metastatic or recurrent, and progressing after conventional chemotherapy
• Glioblastoma, progressing after conventional chemotherapy
• Advanced or metastatic soft tissue sarcoma, residual disease post chemotherapy in the absence of progression, 2nd or subsequent lines
• Advanced or metastatic soft tissue sarcoma progressing post conventional chemotherapy, 3rd or subsequent lines
• Non-small cell lung cancer, 1st or subsequent lines
• ErbB2 positive, advanced or metastatic breast cancer, 2nd or subsequent lines
• Gemcitabine-refractory pancreatic cancer, 2nd or subsequent lines
• Non-cutaneous (ocular or mucosal) melanoma and cutaneous melanoma any line
• GI tract 2nd line residual disease or subsequent lines
• Small Cell Lung cancer 3rd line
• Other solid tumours in which anti-VEGF therapy is judged by the CI to be of possible clinical benefit
3.Must have 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 (meeting detailed criteria)
7. A female is eligible to enter and participate in this study if she is of non-childbearing potential or is taking specified contraceptive measures. A male is eligible to participate if any female partner is of non-childbearing potential or if he is taking specified contraceptive measures.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
1. Known hypertension (blood pressure > 150/90 (± 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: Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary artery bypass graft surgery,Peripheral vascular disease or Raynaud’s phenomenon, Cerebrovascular accident (CVA) including transient ischaemic attack (TIA), 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 artery)
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 central nervous system (CNS) metastases
9. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal 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 of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
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
17. Significant haemoptysis within 8 weeks prior to first dose of pazopanib
18. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient’s safety, provision of informed consent, or compliance to study procedures
19. Unable or unwilling to discontinue use of prohibited medications list 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
20. Treatment with any of the following anti-cancer therapies:
• radiation therapy (single fraction of 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
• chemotherapy, immunotherapy, biologic therapy, investigational therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
• pazopanib or other antiangiogenic treatment (e.g. bevacizumab) within the past 12 weeks
21. 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
22. Any ongoing toxicity from prior ant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method