Clinical trial NCT03557177: Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer
Official title: Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Testicular Cancer
Cardiovascular Diseases
Keywords: cisplatin
flow mediated dilatation
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
First posted: 2018-06-14
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Orchidectomy alone or Orchidectomy plus 1-2 cycles adjuvant cisplatin based chemotherapy or Orchidectomy plus 3-4 cycles cisplatin based chemotherapy

Brief summary: incidence is increasing1,2. Whilst the prognosis is very good with the vast majority of patients cured with orchidectomy alone, those with high risk stage one non seminomatous germ cell cancer (NSCGT) or metastatic disease (NSCGT or seminoma) are treated by surgery followed by chemotherapy. Platinum based chemotherapy is associated with long-term cardiovascular sequelae.

Endothelial dysfunction is a key component of early atherogenesis and the later stages of obstructive atherosclerosis, plaque rupture and thrombus formation. Whilst endothelial toxic effects of BEP chemotherapy appear to be central in the pathophysiology of associated complications, abnormalities in endothelial function as assessed by measures of brachial artery flow-mediated dilatation (FMD) have not demonstrated a consistent effect over time. When assessed within ten weeks of platinum-based chemotherapy9, no change in FMD was observed whilst marked decreases are seen immediately following treatment11 and also one year following treatment12. Therefore, the time-course of endothelial vasomotor impairment remains incompletely defined in a single prospective cohort.

Detailed description: There remains an unmet need to identify a preventive treatment for patients with testicular cancer treated with platinum based chemotherapy to diminish the substantial risk of subsequent cardiovascular events. A future randomised trial of statin therapy in these patients is under consideration and results from this pilot study will inform its design.

Before moving towards interventional studies the proposed pilot study will enable a better understanding of the nature, time-course and dose-dependent effects of the mechanisms contributing to increased cardiovascular risk.

Single-centre, prospective pilot study assessing the cardiovascular effects of treatment with orchidectomy or orchidectomy plus cisplatin based chemotherapy for testicular cancer.

Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of stage 1 or IGCCCG5good or intermediate prognosis metastatic testicular/retroperitoneal germ cell cancer with treatment plan that includes orchidectomy or orchidectomy plus cisplatin based chemotherapy
* Aged between 18 and 65 years inclusive

Exclusion Criteria:

* Unable to provide written, informed consent
* Unable or unwilling to attend for investigations
* Current involvement in a clinical trial
* Anti-platelet therapy at time of enrolment
* Statin or other lipid-lowering therapy at time of enrolment
* Recreational drug use
* Ongoing inflammatory, infective or autoimmune disease
* Other malignant disease diagnosed in previous 5 years
* Previous venous or arterial thrombotic/thromboembolic event

Primary outcomes:
measure: Change in flow-mediated dilatation post cisplatin based chemotherapy
timeFrame: 9 months
Secondary outcomes:
measure: Percentage change in circulating platelet monocyte aggregates post cisplatin based chemotherapy
timeFrame: 9 months
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
Study officials:
affiliation: QEUH, NHS Greater Glasgow and Clyde
name: Ninian Lang, MBChB PhD
role: PRINCIPAL_INVESTIGATOR
References: