NCT01392352

Brief 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. The aim of this study is to find out exactly how the drug causes high blood pressure.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2011

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2011

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 30, 2011

Completed
12 days until next milestone

First Posted

Study publicly available on registry

July 12, 2011

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2015

Completed
Last Updated

February 13, 2020

Status Verified

February 1, 2020

Enrollment Period

3.4 years

First QC Date

June 30, 2011

Last Update Submit

February 12, 2020

Conditions

Renal Cell CarcinomaSoft Tissue SarcomaGlioblastomaOvarian CancerCervical CancerBreast CancerNon-small Cell Lung CancerSmall Cell Lung CancerPancreatic CancerMelanomaGastrointestinal Cancer

Keywords

pazopanibhypertensionforearm blood flow

Outcome Measures

Primary Outcomes (1)

  • Change in endothelial dependent function

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

Secondary Outcomes (1)

  • Change in endothelial independent function

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

Study Arms (1)

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.

Drug: Pazopanib

Interventions

PazopanibDRUG

2 x 400mg pazopanib tablets taken once daily for 12 weeks

Also known as: Votrient
Pazopanib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • 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.
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 33775123DERIVED

MeSH Terms

Conditions

Carcinoma, Renal CellSarcomaGlioblastomaOvarian NeoplasmsUterine Cervical NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungSmall Cell Lung CarcinomaPancreatic NeoplasmsMelanomaGastrointestinal NeoplasmsHypertension

Interventions

pazopanib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital DiseasesNeoplasms, Connective and Soft TissueAstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleGenital Neoplasms, FemaleGenital DiseasesEndocrine System DiseasesGonadal DisordersUterine NeoplasmsUterine Cervical DiseasesUterine DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesDigestive System NeoplasmsDigestive System DiseasesPancreatic DiseasesNeuroendocrine TumorsNevi and MelanomasSkin NeoplasmsGastrointestinal DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Duncan I Jodrell

    University of Cambridge; honorary contract with Cambridge University Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor Duncan Jodrell

Study Record Dates

First Submitted

June 30, 2011

First Posted

July 12, 2011

Study Start

April 1, 2011

Primary Completion

September 1, 2014

Study Completion

September 1, 2015

Last Updated

February 13, 2020

Record last verified: 2020-02

Locations

GB(1)