Clinical Trial Results:
SONATINA: A Phase II Multi-Centre Randomised Controlled Study of Nelfinavir Addition to Radiotherapy Treatment in Neo-Adjuvant Therapy for Rectal Cancer
|
Summary
|
|
EudraCT number |
2010-020621-40 |
Trial protocol |
GB |
Global end of trial date |
20 Jan 2014
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
21 Jul 2016
|
First version publication date |
05 Aug 2015
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
OCTO_021
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
ISRCTN29580179 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
University of Oxford
|
||
Sponsor organisation address |
Clinical Trials and Research Governance, Joint Research Office, Block 60, Churchill Hosp, Old Road , Headington, Oxford, United Kingdom, OX3 7LE
|
||
Public contact |
University of Oxford, University of Oxford, 44 1865 572224, ctrg@admin.ox.ac.uk
|
||
Scientific contact |
University of Oxford, University of Oxford, 44 1865 572224, ctrg@admin.ox.ac.uk
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
10 Feb 2014
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
20 Jan 2014
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 Jan 2014
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To investigate the activity of the drug, Nelfinavir, when it is used to sensitise rectal cancer to radiotherapy treatment to try to make the radiotherapy more effective.
|
||
Protection of trial subjects |
The trial received ethical and regulatory approval, and was run in compliance with the Medicines for Human Use (Clinical Trials) Regulations 2004, and amendments thereafter, the guidelines for Good Clinical Practice, and the applicable policies of the Sponsor, the University of Oxford. Together, these regulations implement the ethical principles of the Declaration of Helsinki (2008) and the regulatory requirements for clinical trials of an investigational medicinal product as set out in the European Union (EU) Directives 2001/20/EC (Clinical Trials) and 2005/28/EC (GCP). Patients also were seen for study assessments every 4 weeks from their last day of radiotherapy for 5 months as consistent with standard NHS therapy.
|
||
Background therapy |
No other background therapies/treatments used. | ||
Evidence for comparator |
No comparator used - single arm study. | ||
Actual start date of recruitment |
05 Apr 2011
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 10
|
||
Worldwide total number of subjects |
10
|
||
EEA total number of subjects |
10
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
5
|
||
From 65 to 84 years |
5
|
||
85 years and over |
0
|
||
|
|||||||||||
|
Recruitment
|
|||||||||||
Recruitment details |
Recruitment was open from April 2011 until January 2014. 8 patients were recruited from a single centre to assess safety prior to extending to the multi-centre randomised trial, and this was then extended to 16 patients. However, because recruitment targets were not met, the study was terminated early with only 10 patients recruited. | ||||||||||
|
Pre-assignment
|
|||||||||||
Screening details |
19 patients were screened, of which 9 were ineligible. 2 patients had a performance status of 3 (eligibility criteria required 0-2), 3 patients were suitable for alternative trials, one patient's primary tumour was not symptomatic, one patient had impaired memory, one patient declined & for one patient the MDT did not feel SCRT was appropriate. | ||||||||||
|
Period 1
|
|||||||||||
Period 1 title |
Baseline
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||
Blinding used |
Not blinded | ||||||||||
|
Arms
|
|||||||||||
|
Arm title
|
Baseline | ||||||||||
Arm description |
- | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Nelfinavir
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||
Routes of administration |
Oral use
|
||||||||||
Dosage and administration details |
Nelfinavir was administered orally 1250mg bd from day-7 (7 days before RT commences on day 1) to day 7 (the last day of RT). Radiotherapy was delivered in fractions of 5 Gy daily from day 1 to day 7. Total dose of radiotherapy is 25 Gy prescribed to the ICRU reference point. Radiotherapy technique could be 3D-conformal or IMRT.
|
||||||||||
|
|||||||||||
|
Period 2
|
|||||||||||
Period 2 title |
Treatment
|
||||||||||
Is this the baseline period? |
No | ||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||
Blinding used |
Not blinded | ||||||||||
|
Arms
|
|||||||||||
|
Arm title
|
Nelfinavir + radiotherapy | ||||||||||
Arm description |
When the trial had been halted for an interim analysis, the decision to extend the initial safety cohort from 8 patients to 16 patients was made, before the decision was made to close the trial early due to slow recruitment. Therefore all the patients in this arm (the safety cohort) received the Nelfinavir + short course radiotherapy (SCRT). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Nelfinavir
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||
Routes of administration |
Oral use
|
||||||||||
Dosage and administration details |
Nelfinavir was administered orally 1250mg bd from day-7 (7 days before RT commences on day 1) to day 7 (the last day of RT). Radiotherapy was delivered in fractions of 5 Gy daily from day 1 to day 7. Total dose of radiotherapy is 25 Gy prescribed to the ICRU reference point. Radiotherapy technique could be 3D-conformal or IMRT.
|
||||||||||
|
|||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Baseline
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Baseline
|
||
Reporting group description |
- | ||
Reporting group title |
Nelfinavir + radiotherapy
|
||
Reporting group description |
When the trial had been halted for an interim analysis, the decision to extend the initial safety cohort from 8 patients to 16 patients was made, before the decision was made to close the trial early due to slow recruitment. Therefore all the patients in this arm (the safety cohort) received the Nelfinavir + short course radiotherapy (SCRT). | ||
|
|||||||||||||||||||
End point title |
Incidence of any CTCAE grade 3 or higher toxicities [1] | ||||||||||||||||||
End point description |
The primary outcome for the SONATINA safety cohort analysis is safety measured by incidence of any grade 3 or higher non-haematological or haematological toxicity (according to CTCAE v 4.0) up to 28 days post-SCRT. Toxicities that occurred up to 28 days post-SCRT have been summarised by Adverse Event Term. No formal comparison has been made as there is only one treatment arm.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Up to 28 days post the last day of radiotherapy treatment
|
||||||||||||||||||
| 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: The primary outcome for the SONATINA safety cohort analysis was safety measured by incidence of any grade 3 or higher non-haematological or haematological toxicity (according to CTCAE v 4.0) up to 28 days post-SCRT. Toxicities that occurred up to 28 days post-SCRT have been summarised. No formal comparison has been made as there is only one treatment arm. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||
End point title |
TCD in biopsy taken 7 days from last fraction of protocol radiotherapy. [2] | ||||||||||||||
End point description |
The primary aim of the main SONATINA trial was to investigate the effect of Nelfinavir (the study drug) added to short-course radiotherapy in improving response rate in patients with rectal cancer patients, whilst testing the feasibility of using Tumour Cell Density (TCD) in the primary tumour to measure response rate. The primary tumour TCD of each patient was measured before and after their Nelfinavir and SCRT treatment.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Before and after the Nelfinavir and SCRT treatment
|
||||||||||||||
| Notes [2] - 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: The primary outcome for the SONATINA trial (before it was closed due to slow recruitment) was Tumour Cell Density (TCD) in primary tumour biopsy taken 7 days from last faction of SCRT. No formal comparison has been made as there is only one treatment arm, and only a very small number of patients. |
|||||||||||||||
|
|||||||||||||||
Attachments |
TCD comparison: Pre to Post SCRT |
||||||||||||||
| Notes [3] - One patient had no tumour in their post treatment biopsy |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Radiological response of primary tumour at 8 weeks post SCRT evaluated by RECIST | ||||||||||||||
End point description |
Radiological response evaluated by RECIST (version 1.1) assessment of primary tumour on MRI at 8 weeks post-SCRT. 8 out of 10 patients (80%) can be classed as responders, as they had Complete Response, Partial Response or Stable Disease at 8 weeks. Patient ST1002 had Progressive Disease at 8 weeks, and ST1010 is Not Evaluable as they had died before the 8 week assessment, so these two patients are classed as non-responders.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
8 weeks post short course radiotherapy (SCRT) treatment
|
||||||||||||||
|
|||||||||||||||
| Notes [4] - One patient died before their 8 week scan |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||
End point title |
Radiological response of primary tumour at 8 weeks post SCRT evaluated by mrTRG assessment | ||||||||||
End point description |
Radiological response evaluated by mrTRG assessment of primary tumour on MRI at 8 weeks post-SCRT. As well as being assessed with RECIST criteria, the patients’ primary tumours were also assessed using mrTRG scores by two radiologists. If the two radiologists did not agree in their assessment, there was a third radiologist’s opinion. The overall mrTRG score that was assigned to each patient is presented. 5/9 (56%) of the mrTRG assessed SONATINA patients’ primary tumours were classed as good overall by the radiologists.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
8 weeks post short course radiotherapy (SCRT) treatment.
|
||||||||||
|
|||||||||||
| Notes [5] - One patient died before their 8 week scan |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Proportion of patients proceeding to resectional pelvic surgery | ||||||||||
End point description |
The proportion of SONATINA patients proceeding to pelvic surgery within 6 months from last fraction of radiotherapy. No SONATINA patients proceeded to have pelvic surgery within 6 months of their radiotherapy treatment.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Within 6 months from last fraction of short course radiotherapy (SCRT)
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 6 months post-SCRT
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Nelfinivir + radiotherapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Nelfinavir + radiotherapy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||
Substantial protocol amendments (globally) |
|||||||
| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
14 Jun 2012 |
The main purpose of this amendment was to clarify the definition of the safety cohort and to amend the definition of end of trial. |
||||||
17 Sep 2012 |
The main purpose of this amendment was to expand the safety cohort from 8 to 16 patients since the levels of grade 3/4 toxicity experienced were slightly, but not significantly, higher than one would expect from radiotherapy alone. So we needed to study more patients in order to be able to tell whether there is any significant toxicity from the combination of radiotherapy and Nelfinavir being tested in this trial. |
||||||
Interruptions (globally) |
|||||||
| Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| Early termination due to slow recruitment leading to a very small number of subjects analysed | |||||||
