Clinical Trial Results:
A phase II study of Cabazitaxel chemotherapy in relapsed locally advanced and/or metastatic carcinoma of the penis.
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Summary
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EudraCT number |
2014-002336-14 |
Trial protocol |
GB |
Global end of trial date |
14 Aug 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Sep 2018
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First version publication date |
26 Sep 2018
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Other versions |
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Summary report(s) |
PFS and OS Curves |
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 |
ON/2012/4233
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT03114254 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
JAVA-P: ON/2012/4233 | ||
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Sponsors
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Sponsor organisation name |
University Hospitals Bristol NHS Foundation Trust, Trust HQ, Marlborough Street, Bristol, bs3 1ta, United Kingdom
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Sponsor organisation address |
Trust HQ, Marlborough Street, Bristol, Bristol, United Kingdom, bs3 1ta
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Public contact |
JAVA P Study Manager, University Hospitals Bristol NHS Foundation trust, +44 1173427860, javap@uhbristol.nhs.uk
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Scientific contact |
JAVA P Study Manager/Chief Investigator - Prof Amit Bahl, University Hospitals Bristol NHS Foundation trust, +44 1173427860, javap@uhbristol.nhs.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 |
27 Jul 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Aug 2017
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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 determine the activity of Cabazitaxel chemotherapy in relapsed cancer of the penis as assessed by objective response rate.
The primary endpoint is objective response rate defined as complete response and partial response recorded from the start of the treatment to completion of 6 cycles of treatment determined by radiological response assessment
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Protection of trial subjects |
Full trial sample size was calculated to be 17 patients, with a stopping rule at 9 patients. The protocol stated that recruitment would be stopped at the point at which ‘there is a 99% chance that the response rate is less than 60%. If no patients are seen to respond to treatment, the study will stop at the point at which 9 patients results are known’. Of the first 9 patients recruited 0 patients responded to treatment. The IDMC met on 06/01/2017 and recommended no further recruitment into the trial in adherence to the stopping rule. According to the protocol ‘the study is deemed to have ended 5 years after the last patient has undergone chemotherapy’. The trial therefore ended having recruited 9 patients with the end of trial being the date of the last patient last visit which was 14/08/2017 (the date the last patient died).
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Background therapy |
Docetaxel, Cisplatin, 5FU triplet combination therapy is the standard of care for specific penile cancer patients in several UK cancer centres, However, on relapse there is no UK standard secondary chemotherapy treatment available. Therefore this study presented a second line treatment option for these subset of patients, which these patients would not otherwise receive. | ||
Evidence for comparator |
This study had no comparator as per above, this treatment was in addition to first line treatment. | ||
Actual start date of recruitment |
01 Oct 2014
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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: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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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) |
7
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Cancer of the penis is a rare disease. Discussion within the supra-network MDT of all eligible patients is encouraged/ To enable recruitment, this study has been supported by the NCRI Penile Cancer Clinical Studies Subgroup, recognizing that there are no available treatment options in this setting. | ||||||
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Pre-assignment
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Screening details |
Patients must be adult males with histologically-proven SCC of the penis. SCC of the penile urethra is also allowed. Patients must be stage M1 or; M0TxN3; M0TxN2; M0TxN1, M0T4. Patients must have received first line treatment previously and have an ECOG status 0-2. They must not have had previous cabazitaxel treatment. | ||||||
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Period 1
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Period 1 title |
Overall trial - baseline (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Cabazitaxel | ||||||
Arm description |
Platinum based combination chemotherapy is the standard of care for patients with symptomatic advanced/metastatic penile cancer. However, on relapse there is no standardised second line treatment in the UK. This trial aimed to evaluate the activity, safety and tolerability of cabazitaxel as second line treatment in relapsed penile cancer. A phase II single arm trial was designed to recruit 17 patients with the primary endpoint being objective response rate – ORR (complete response plus partial response). | ||||||
Arm type |
Non RCT | ||||||
Investigational medicinal product name |
Cabazitaxel
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Investigational medicinal product code |
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Other name |
Jevtana
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Pharmaceutical forms |
Solution for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dose: 25mg/m2 capped at BSA 2.25
Formulation: 60 mg concentrate and solvent for solution for IV infusion
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial - baseline
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Reporting group description |
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End points reporting groups
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Reporting group title |
Cabazitaxel
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Reporting group description |
Platinum based combination chemotherapy is the standard of care for patients with symptomatic advanced/metastatic penile cancer. However, on relapse there is no standardised second line treatment in the UK. This trial aimed to evaluate the activity, safety and tolerability of cabazitaxel as second line treatment in relapsed penile cancer. A phase II single arm trial was designed to recruit 17 patients with the primary endpoint being objective response rate – ORR (complete response plus partial response). | ||
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End point title |
Overall response rate (ORR) [1] | ||||||||||
End point description |
The primary endpoint is objective response rate defined as complete response and partial response recorded from the start of the treatment to completion of 6 cycles of treatment determined by radiological response assessment
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End point type |
Primary
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End point timeframe |
Within 6 cycles 3 weekly chemotherapy (18 weeks)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: None of the patients recruited achieved the primary endpoint of objective response rate (ORR), after 6 cycles of cabazitaxel, therefore the null hypothesis was accepted. An interim analysis was planned based on the premise that if no patient achieved ORR among the first 9 patients treated, then the null hypothesis that the ORR is <10% (based on a response rate of 0.25) would be accepted, and the trial would be stopped (α = 0.05, Simon's 2 stage design). |
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End point title |
Progression Free Survival | ||||||||
End point description |
Progression-free survival (defined as the time from date of consent to the first of one of the following: development of radiological disease progression (RECIST 1.1) or death from any cause, whichever comes first).;
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End point type |
Secondary
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End point timeframe |
With 4 months of the patients consenting onto the clinical trial.
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End point title |
Overall Survival | ||||||||
End point description |
Overall Survival defined as the time from date of consent to death from any cause.
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End point type |
Secondary
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End point timeframe |
Within 15 months of the patients being consented for the clinical trial.
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Attachments |
Untitled (Filename: PFS and OS curves.docx) |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were recorded from cycle 1 day 1 of chemotherapy until 6 months post the last date of treatment.
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Adverse event reporting additional description |
AEs were reported and graded according to CTCAE v4.03. Causality was assigned by the PI or Co-I at site referring to the RSI.
There were 6 SAEs reported.
Overall there were 59 adverse events reported.
The adverse events reported below are only adverse events that are deemed related to the IMP (25 events)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.03
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Reporting groups
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Reporting group title |
All patients
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 May 2015 |
• Amendment 1 - addition of Clatterbridge Cancer Centre as a site; administration of pegylated GCSF allowed; avoidance of grapefruit juice; clarification of restrictions for use of CYP3A inhibitors and inducers. |
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18 Dec 2015 |
• Amendment 2 – addition of Treliske Hospital as a site; confirmation that prior chemotherapy except cabazitaxel is allowed; clarification of the trial second line status in the title; removal of the TSC.
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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 | |||
