Clinical Trial Results:
A randomised trial to determine the impact of timing of surgery and chemotherapy in newly diagnosed patients with advanced epithelial ovarian, primary peritoneal or fallopian tube carcinoma
Summary
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EudraCT number |
2007-004429-45 |
Trial protocol |
GB |
Global end of trial date |
16 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Jul 2016
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First version publication date |
09 Jul 2016
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Other versions |
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Summary report(s) |
Chorus Lancet paper Chorus Lancet paper - Supplementary Appendix |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CHORUS
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Additional study identifiers
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ISRCTN number |
ISRCTN74802813 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
MRC Clinical Trials Unit at UCL
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Sponsor organisation address |
Aviation House, 125 Kingsway, London, United Kingdom, WC2B 6NH
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Public contact |
General enquiries office, MRC Clinical Trials Unit at UCL, 0044 020 7670 4700, enquiries@ctu.mrc.ac.uk
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Scientific contact |
General enquiries office, MRC Clinical Trials Unit at UCL, 0044 020 7670 4700, enquiries@ctu.mrc.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 May 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Oct 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety and efficacy of neoadjuvant chemotherapy i.e. chemotherapy given before and after primary surgery compared to standard surgery followed by chemotherapy
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Protection of trial subjects |
National ethical and regulatory approvals were obtained in the UK and New Zealand, with local approvals obtained at each centre. The IDMC and independent Trial Steering Committees oversaw the running of the trial. All participating centres were public
hospitals that regularly undertook treatment of ovarian cancer with multidisciplinary teams that included specialist surgeons, oncologists, and pathologists.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Mar 2004
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 537
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Country: Number of subjects enrolled |
New Zealand: 13
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Worldwide total number of subjects |
550
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EEA total number of subjects |
537
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
260
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From 65 to 84 years |
284
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85 years and over |
6
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Recruitment
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Recruitment details |
Recruitment ran from 5th March 2004 to 26th August 2010. | |||||||||
Pre-assignment
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Screening details |
At screening, all women had a clinical assessment, an imaging test (a CT or MRI scan of the abdomen and pelvis, and a radiograph of the chest), and concentrations of serum tumour markers measured (CA125 and CEA). | |||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Primary surgery | |||||||||
Arm description |
Primary surgery followed by six cycles of chemotherapy. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The recommended treatment doses as defined in the protocol are:
• Single-agent Carboplatin either
o Target AUC5 x (51Cr-EDTA clearance + 25)mg or
o Target AUC6 x (calculated GFR or 24-hour urinary clearance + 25)mg
• Carboplatin in combination with Paclitaxel
o Paclitaxel 175mg/m2
o Carboplatin either
-Target AUC5 x (51Cr-EDTA clearance + 25)mg or
-Target AUC6 x (calculated GFR or 24-hour urinary clearance + 25)
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The recommended treatment doses as defined in the protocol are:
Carboplatin in combination with Paclitaxel
o Paclitaxel 175mg/m2
o Carboplatin either
-Target AUC5 x (51Cr-EDTA clearance + 25)mg or
-Target AUC6 x (calculated GFR or 24-hour urinary clearance + 25)
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Arm title
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Primary chemotherapy | |||||||||
Arm description |
Three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The recommended treatment doses as defined in the protocol are:
• Single-agent Carboplatin either
o Target AUC5 x (51Cr-EDTA clearance + 25)mg or
o Target AUC6 x (calculated GFR or 24-hour urinary clearance + 25)mg
• Carboplatin in combination with Paclitaxel
o Paclitaxel 175mg/m2
o Carboplatin either
-Target AUC5 x (51Cr-EDTA clearance + 25)mg or
-Target AUC6 x (calculated GFR or 24-hour urinary clearance + 25)
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The recommended treatment doses as defined in the protocol are:
Carboplatin in combination with Paclitaxel
o Paclitaxel 175mg/m2
o Carboplatin either
-Target AUC5 x (51Cr-EDTA clearance + 25)mg or
-Target AUC6 x (calculated GFR or 24-hour urinary clearance + 25)
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Baseline characteristics reporting groups
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Reporting group title |
Primary surgery
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Reporting group description |
Primary surgery followed by six cycles of chemotherapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Primary chemotherapy
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Reporting group description |
Three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Primary surgery
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Reporting group description |
Primary surgery followed by six cycles of chemotherapy. | ||
Reporting group title |
Primary chemotherapy
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Reporting group description |
Three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. |
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End point title |
Overall survival | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
OS at data cut-off of 31st May 2014.
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Statistical analysis title |
Overall survival | ||||||||||||
Statistical analysis description |
Hazard ratio to assess non-inferiority. Upper limit of 90% CI needs to exclude 1.18 to meet pre-specified criteria for non-inferiority.
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Comparison groups |
Primary surgery v Primary chemotherapy
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Number of subjects included in analysis |
550
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
Method |
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Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.87
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Confidence interval |
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level |
90% | ||||||||||||
sides |
1-sided
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lower limit |
- | ||||||||||||
upper limit |
0.98 |
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End point title |
Progression Free Survival | ||||||||||||
End point description |
PFS measured from date of randomisation to date of death or confirmed progression. Patients without a date of death are censored at the date they were last known to be alive and progression free.
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End point type |
Secondary
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End point timeframe |
PFS up to data cut-off point of 31st May 2014.
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Statistical analysis title |
PFS | ||||||||||||
Statistical analysis description |
Hazard ratio of PFS.
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Comparison groups |
Primary surgery v Primary chemotherapy
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Number of subjects included in analysis |
550
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.91
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.76 | ||||||||||||
upper limit |
1.09 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse event reporting was scheduled throughout follow-up, but summaries are focussed on the treatment period due to the scarcity of reporting after that point.
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Adverse event reporting additional description |
Specific SAE's are listed if >1% of patients in either arm were affected. All other SAE's are grouped under "Other".
Non-serious adverse events were not routinely reported, other than through chemotherapy toxicity reports, and are not included here.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
3.0
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Reporting groups
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Reporting group title |
Primary surgery
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Reporting group description |
Primary surgery followed by six cycles of chemotherapy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Primary chemotherapy
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Reporting group description |
Three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Non-serious adverse events were not routinely collected, other than reporting through chemotherapy toxicities, and are not included here. |
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/26002111 |