HYPAZ: Hypertension Induced by Pazopanib

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Cambridge University Hospitals NHS Foundation Trust
Sponsor:
Collaborators:
University of Cambridge
GlaxoSmithKline
Information provided by (Responsible Party):
Duncan Jodrell, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01392352
First received: June 30, 2011
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: HYPAZ: An Open-label Investigation Into Hypertension Induced by Pazopanib Therapy

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Change in endothelial dependent function [ Time Frame: Measured over 12 weeks, or at the onset of hypertension whichever occurs first ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in endothelial independent function [ Time Frame: Measured over 12 weeks, or at onset of hypertension, whichever occurs first ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 52
Study Start Date: April 2011
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib Drug: Pazopanib
2 x 400mg pazopanib tablets taken once daily for 12 weeks
Other Name: Votrient

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 up.
  2. 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 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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392352

Contacts
Contact: Alex Jonson alex.jonson@addenbrookes.nhs.uk

Locations
United Kingdom
Cambridge University Hospitals NHS Foundation Trust Recruiting
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Contact: Alex Jonson       alex.jonson@addenbrookes.nhs.uk   
Principal Investigator: Duncan Jodrell, DM MSc FRCP         
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
University of Cambridge
GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Duncan Jodrell, Professor Duncan Jodrell, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01392352     History of Changes
Other Study ID Numbers: A091962, 2010-021613-23
Study First Received: June 30, 2011
Last Updated: May 16, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
pazopanib
hypertension
forearm blood flow

Additional relevant MeSH terms:
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
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014