Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000923460
Ethics application status
Approved
Date submitted
4/07/2016
Date registered
12/07/2016
Date last updated
11/01/2023
Date data sharing statement initially provided
11/01/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Prospective Observational Study Assessing The Role of IL-6 On The Platelet Protective Effects of Paclitaxel-based Chemotherapy in Patients with Epithelial Ovarian Cancer
Scientific title
A Prospective Observational Study Assessing The Role of IL-6 On The Platelet Protective Effects of Paclitaxel-based Chemotherapy in Patients with Epithelial Ovarian Cancer
Secondary ID [1] 289607 0
Nil known
Universal Trial Number (UTN)
Trial acronym
IL6PT-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epithelial Ovarian Cancer 299392 0
Condition category
Condition code
Cancer 299378 299378 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study is a prospective observational study assessing the role of IL-6 in the platelet-protective effects of paclitaxel-based chemotherapy in patients with epithelial ovarian cancer (EOC). Participants on this study would be receiving the same chemotherapy treatment regimen if they were not participating in this study and the doses and schedule for this study have been chosen based on the standard doses of carboplatin and paclitaxel used for first-line neo-adjuvant chemotherapy. The chemotherapy regimens will be given as per local unit guidelines of Icon Cancer Care, Johns Hopkins and MD Anderson and Gustave Roussy Gynaecological Oncology clinics until the point of completing at least 3-4 cycles of treatment or prior study.

Baseline evaluations are to be performed within four weeks prior to the start of treatment, include complete medical history; informed consent; complete physical examination; height; weight; performance status; vital signs; standard laboratory assessments; CA-125 tumour marker; urine hCG; standard of care imaging; ECG and blood sampling. Day 1 evaluations will include physical examination; weight; performance status; vital signs; standard laboratory assessments; assessment of adverse events and pharmacodynamic blood sampling. For patients on weekly treatments, evaluations on day 8 and day 15 will include physical examination; weight; performance status; vital signs; standard laboratory assessments; assessment of adverse events and pharmacodynamic blood sampling. End of study evaluations at 4 weeks after the last cycle of treatment will be consistent with the day 1 schedule listed above.

The primary difference between standard of care and this research is the collection of 10 ml blood for plasma samples for pharmacodynamic assessments at pre-treatment with each cycle of chemotherapy. Specifically there will be a sample collected during screening / baseline, another sample at every day 1 for 3 cycles, potentially another 2 samples at day 8 and 15 for 3 cycles depending upon which chemotherapy regimen is chosen in addition to a final sample at 4 weeks after the last cycle of chemotherapy for a total maximum of 11 samples of 10ml for a total of 48 participants.
Intervention code [1] 295218 0
Diagnosis / Prognosis
Comparator / control treatment
There is no control or comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298839 0
Correlation assessment between IL-6 levels in plasma measured by ELISA and serum platelet levels
Timepoint [1] 298839 0
Plasma sample collected during screening / baseline, another plasma sample at every day 1 for 3 cycles, potentially another 2 plasma samples at day 8 and 15 for 3 cycles depending upon which chemotherapy regimen is chosen in addition to a final plasma sample at 4 weeks after the last cycle of chemotherapy for a total maximum of 11 blood collections of 10ml for a total of 48 participants.
Secondary outcome [1] 325381 0
Correlation between plasma TPO levels (measured by ELISA) with IL-6 concentrations
Timepoint [1] 325381 0
Plasma sample collected during screening / baseline, another plasma sample at every day 1 for 3 cycles, potentially another 2 plasma samples at day 8 and 15 for 3 cycles depending upon which chemotherapy regimen is chosen in addition to a final plasma sample at 4 weeks after the last cycle of chemotherapy for a total maximum of 11 blood collections of 10ml for a total of 48 participants.
Secondary outcome [2] 325407 0
Measurement of CRP (acute phase protein significantly induced by IL-6)
Timepoint [2] 325407 0
Plasma sample collected during screening / baseline, another plasma sample at every day 1 for 3 cycles, potentially another 2 plasma samples at day 8 and 15 for 3 cycles depending upon which chemotherapy regimen is chosen in addition to a final plasma sample at 4 weeks after the last cycle of chemotherapy for a total maximum of 11 blood collections of 10ml for a total of 48 participants.
Secondary outcome [3] 325408 0
The number of dose limiting toxicities (DLT) will be assesswed using NCI CTCAE Version 4.0. as the mtool for assessment. DLTs will be defined as any of the following: Neutropaenia CTC grade 4 for greater than or equal to 5 days duration; Febrile neutropaenia or infection with neutropaenia (CTC grade 4); Thrombocytopaenia CTC grade 4 a) for greater than or equal to 5 days or b) associated with active bleeding or c) requiring platelet transfusion; Non-haematological toxicity CTC grade greater than or equal to 3 (excluding alopecia, nausea and vomiting) or Drug-related death
Timepoint [3] 325408 0
From day 1 of cycle 1 to 4 weeks after the last treamtnet

Eligibility
Key inclusion criteria
Women with histologically confirmed epithelial ovarian cancer.
Patients considered for neoadjuvant chemotherapy at the participating centres (i.e. planned for carboplatin and paclitaxel first-line neo-adjuvant chemotherapy at the Icon Cancer Care, Johns Hopkins and MD Anderson and Gustave Roussy Gynaecological Oncology clinics)
Age greater than or equal to 18 years
WHO performance status of 0, 1 or 2
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Unresolved bowel obstruction
Previous lines of chemotherapy
Radiotherapy within the preceding 3 weeks
Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer.
Known leptomeningeal involvement or intracranial disease
Pregnant or lactating females.
Inability or unwillingness to give informed consent.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
48 patients from clinics within the ICON Cancer Care, The John Hopkins, Gustave Roussy Cancer Institute and MD Anderson Cancer Centres will be recruited with an estimated time to accrual of 12 months.

A sample size of 48 (16 x 3) achieves 80% power to detect a correlation coefficient between IL-6 and platelet counts of 0.39 using a two-sided test with significance level of 0.05.

Analysis Plan

We will use descriptive statistics and graphs to summarize the demographic and clinical characteristics of patients by thrombocytosis (defined as platelet count greater than 450). Spearman’s correlation will be calculated between IL-6 and platelet counts. We will also conduct a t-test to compare the mean IL-6 concentrations by thrombocytosis. Transformations of IL-6 will be performed if necessary. If these transformations do not yield a normal distribution, we will conduct a Wilcoxon rank sum test. Furthermore, we will conduct logistic regression analysis regressing platelet protection (Yes/No) on IL-6 concentration. Odds ratios and 95% confidence intervals will be reported. We will control for demographic and clinical variables if appropriate.

Similar analysis (Spearman’s, t-test, etc.) will be conducted to determine the influence of IL-6 on plasma thrombopoetin levels. Simple linear regression and logistic regression will be conducted regressing thrombocytosis on inflammatory markers to determine if these inflammatory markers in the blood are predictive of platelet protection

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
26/06/2016
Date of last participant enrolment
Anticipated
31/12/2018
Actual
16/02/2017
Date of last data collection
Anticipated
31/03/2019
Actual
24/03/2017
Sample size
Target
16
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 6123 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [2] 6124 0
Icon Cancer Care Wesley - Auchenflower
Recruitment hospital [3] 6125 0
Icon Cancer Care Southport - Southport
Recruitment hospital [4] 6126 0
Icon Cancer Care Chermside - Chermside
Recruitment postcode(s) [1] 13561 0
4101 - South Brisbane
Recruitment postcode(s) [2] 13562 0
4066 - Auchenflower
Recruitment postcode(s) [3] 13563 0
4215 - Southport
Recruitment postcode(s) [4] 13564 0
4032 - Chermside
Recruitment outside Australia
Country [1] 8009 0
France
State/province [1] 8009 0
Villejuif
Country [2] 8010 0
United States of America
State/province [2] 8010 0
Texas and Baltimore

Funding & Sponsors
Funding source category [1] 293990 0
Charities/Societies/Foundations
Name [1] 293990 0
Icon Cancer Foundation
Country [1] 293990 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Icon Cancer Foundation
Address
Floor 1, 22 Cordelia Street,
South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 292807 0
None
Name [1] 292807 0
Address [1] 292807 0
Country [1] 292807 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295406 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 295406 0
129 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 295406 0
Australia
Date submitted for ethics approval [1] 295406 0
16/03/2016
Approval date [1] 295406 0
14/04/2016
Ethics approval number [1] 295406 0
2016-03-200

Summary
Brief summary
Summary
People diagnosed with ovarian cancer will receive chemotherapy either prior to (neoadjuvant chemotherapy) or following surgery (adjuvant chemotherapy). Previous research has confirmed the importance of treating people with ovarian cancer with regimes that contain carboplatin. As with all chemotherapies there are side effects associated with carboplatin treatment which include fatigue, nausea, vomiting and altered kidney function. More importantly, carboplatin treatment can have a significant effect on the bone marrow of people being treated, leading to anaemia and immunosuppression. In particular, carboplatin can decrease the number of cells known as platelets which are responsible for blood clotting. Therefore people whose platelet cell count is low as a result of carboplatin treatment are at risk of bleeding and the treatment doses and timing are affected.

Currently, there is no adequate explanation for this observation. There have been reports confirming that paclitaxel can increase the blood concentrations of particular proteins associated with inflammation (cytokines) that are also responsible for stimulating platelet production. One such cytokine is called interleukin-6 (IL-6). This study aims to investigate whether the IL-6 protein is responsible for protecting platelets in people receiving paclitaxel.

Who is it for?

You may be eligible to join this study if you are a female aged 18 years or above, with histologically confirmed epithelial ovarian cancer considered for neoadjuvant chemotherapy.

Study details
Participants in this study will receive the standard doses of carboplatin and paclitaxel used for first-line chemotherapy in the ICON Cancer Care, Johns Hopkins and MD Anderson and Gustave Roussy Gynaecological Oncology units. Chemotherapy regimens will be given as per local unit guidelines until the point of completing at least 3-4 cycles of treatment or prior study withdrawal. The primary difference between standard of care and this research is the collection of 10 ml blood for plasma samples for pharmacodynamic assessments at pre-treatment with each cycle of chemotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67190 0
A/Prof Jermaine Coward
Address 67190 0
Icon Cancer Centre South Brisbane, Level 5 293 Vulture Street, South Brisbane QLD 4101
Country 67190 0
Australia
Phone 67190 0
+61737374500
Fax 67190 0
+61737374501
Email 67190 0
[email protected]
Contact person for public queries
Name 67191 0
Ms Mel Grand
Address 67191 0
Icon Institute of Innovation and Research, Level 1, 22 Cordelia Street South Brisbane QLD 4101
Country 67191 0
Australia
Phone 67191 0
+61 437067494
Fax 67191 0
+61 7 37374555
Email 67191 0
[email protected]
Contact person for scientific queries
Name 67192 0
A/Prof Jermaine Coward
Address 67192 0
Icon Cancer Centre South Brisbane, Level 5 293 Vulture Street, South Brisbane QLD 4101
Country 67192 0
Australia
Phone 67192 0
+61737374500
Fax 67192 0
+61737374501
Email 67192 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.