Prostate Cancer
Conditions
Brief summary
The WINGMEN trial aims to understand how a hormone-like protein called insulin-like growth factor (IGF) helps prostate cancers grow and become aggressive. IGF is required for normal development, and also helps cancers grow and spread. Men with high blood IGF are at increased risk of developing prostate cancer, and tall men are more likely to get aggressive prostate cancer. The WINGMEN trial will recruit 30 men with prostate cancer who have been offered an operation to remove the prostate. Most men have to wait 4-5 weeks between a decision to have prostate removal surgery, and actually having the operation. In this 4-5 week window we will offer treatment with a new IGF-blocker drug called xentuzumab. The drug is provided by Boehringer Ingelheim and the trial is funded by Prostate Cancer UK. Xentuzumab will be given as an outpatient by once weekly intravenous infusion (drip) in the Early Phase Clinical Trials Unit, Oxford Cancer Centre, Churchill Hospital. In other trials, xentuzumab is being tested in patients with advanced cancer, and is proving to be well-tolerated. After the 4-week treatment, WINGMEN trial patients will have routine prostate removal surgery. Samples of blood and prostate cancer that are surplus to diagnostic need will be taken from the diagnostic prostate biopsy (pre-xentuzumab) and the cancer removed at surgery (after xentuzumab) for research tests. These samples will be compared to measure how effectively xentuzumab reduces signs of tumour growth, and identify which genes and proteins are switched on or off by xentuzumab, and which may therefore be important in helping IGF promote prostate cancer growth. The information we get from the WINGMEN trial may help us to improve treatment of men with prostate cancer, with the long-term aim of reducing the risk of aggressive prostate cancer
Interventions
DRUGXentuzumab
The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Sponsors
Prostate Cancer UK
Boehringer Ingelheim
University of Oxford
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase 0 'window of opportunity' study testing whether xentuzumab blocks IGF signalling and markers of growth in men with localised prostate cancer scheduled for radical prostatectomy
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient will be eligible for inclusion in this study if all of the following criteria apply. 1. Men with prostate adenocarcinoma confirmed on prostate biopsy and with sufficient cancer-containing biopsy tissue surplus to diagnostic need to provide 2 sections for primary endpoint analysis. 2. Scheduled for open or robotic radical prostatectomy 3. Age ≥ 18 years 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 1) 5. The patient is willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the study 6. Participant is willing and able to give informed consent. 7. Participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 70 days thereafter. 8. Adequate hematologic, renal and hepatic function, defined as follows: Laboratory Test Value required Hemoglobin (Hb) ≥90g/L White Blood Count (WBC) \>2.5 x 10\*9/L Absolute Neutrophil Count (ANC) ≥ 1.5 x10\*9/L Platelet count ≥ 100 x 10\*9/L AST, ALT, and alkaline phosphatase ≤ 2.5 x upper limit of normal eGFR\* ≥30ml/min \*eGFR calculated by Cockcroft & Gault formula,
Exclusion criteria
* A patient will not be eligible for the trial if any of the following apply: 1. Treated with systemic corticosteroids, insulin, metformin, other oral hypoglycemic agent, or anti-androgens in the 28 days prior to first dose of study drug 2. Diabetes mellitus 3. Previous prostate radiotherapy 4. Current or previous treatment with xentuzumab or other IGF or GH -modifying therapy 5. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV 6. Treatment with any other investigational agent, or treatment in another interventional clinical trial within 28 days prior to enrolment 7. Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change of Phospho-IGF-1R Positive Tumour Cells Following Treatment With Xentuzumab | From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total. | Diagnostic biopsies (pre-treatment) and in-theatre cores (post-treatment) were stained with phospho-IGF-1R. Percentage of positively stained tumour cells in each sample were compared and the percentage change between timepoints was quantified. A negative percentage change indicates a reduction in phospho-IGF-1R in post-treatment samples. This endpoint was designed to assess the amount of IGF pathway inhibition induced by xentuzumab. |
| Percentage Change of Phospho-S6 Positive Tumour Cells Following Treatment With Xentuzumab | From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total. | Diagnostic biopsies (pre-treatment) and in-theatre cores (post-treatment) were stained by phospho-S6. Percentage of positively stained tumour cells in each sample were compared and the percentage change between timepoints was quantified. A negative percentage change indicates a reduction in phospho-S6 in post-treatment samples. This endpoint was designed to assess the amount of IGF pathway inhibition induced by xentuzumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had at Least 4 Doses of Xentuzumab and Proceeded to Have Surgery Per the Protocol Schedule | From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total. | This endpoint was a measure of feasibility of the treatment schedule in the pre-operative setting. |
| Median Delay in Surgery in Participants Who Had More Than 4 Doses of Xentuzumab (and Whose Surgery Was Delayed by Factors Other Than Trial Treatment) | From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total. | All participants who had more than 4 doses of xentuzumab were considered to have had their surgery delayed by factors other than trial treatment. Per protocol, all participants who had delayed surgery received additional weekly doses of xentuzumab. Reason for delay was not recorded as part of the study dataset. This endpoint was a measure of feasibility of the treatment schedule in the pre-operative setting. |
| Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial | From consent at week -1 to the end of study visit at up to 19 weeks | This endpoint was designed to assess safety and tolerability of xentuzumab administered in the pre-prostatectomy setting. AEs & SAEs were graded using CTCAE v5.0, with higher grades considered to be worse outcomes. |
| Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial | From consent at week -1 to the end of study visit at up to 19 weeks | Number of patients with any TRAE from the time of consent to the end of study visit. TRAEs are AEs that are investigator-determined to be definitely, probably or possibly related to treatment with xentuzumab and graded using CTCAE v5.0, with higher grades considered to be worse outcomes. This endpoint was designed to assess safety and tolerability of xentuzumab administered in the pre-prostatectomy setting. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Xentuzumab All patients will be allocated to receive Xentuzumab
Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Completed treatment with IMP but disease progressed prior to surgery. | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Xentuzumab |
|---|---|
| Age, Continuous | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United Kingdom | 27 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 24 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Percentage Change of Phospho-IGF-1R Positive Tumour Cells Following Treatment With Xentuzumab
Diagnostic biopsies (pre-treatment) and in-theatre cores (post-treatment) were stained with phospho-IGF-1R. Percentage of positively stained tumour cells in each sample were compared and the percentage change between timepoints was quantified. A negative percentage change indicates a reduction in phospho-IGF-1R in post-treatment samples. This endpoint was designed to assess the amount of IGF pathway inhibition induced by xentuzumab.
Time frame: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.
Population: Units given accounts for a pre-treatment and post-treatment sample per participant. Number analysed excludes samples from 6 participants that were missing either the pre-treatment or post-treatment sample, or could not be analysed for other reasons.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Xentuzumab | Percentage Change of Phospho-IGF-1R Positive Tumour Cells Following Treatment With Xentuzumab | -8.28 Percentage change Phospho-IGF-1R+ cells |
Primary
Percentage Change of Phospho-S6 Positive Tumour Cells Following Treatment With Xentuzumab
Diagnostic biopsies (pre-treatment) and in-theatre cores (post-treatment) were stained by phospho-S6. Percentage of positively stained tumour cells in each sample were compared and the percentage change between timepoints was quantified. A negative percentage change indicates a reduction in phospho-S6 in post-treatment samples. This endpoint was designed to assess the amount of IGF pathway inhibition induced by xentuzumab.
Time frame: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.
Population: Units analysed describes pre-treatment and post-treatment sample for each participant. Number analysed excludes 10 participants that were missing either the pre-treatment or post-treatment sample, or could not be analysed for other reasons.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Xentuzumab | Percentage Change of Phospho-S6 Positive Tumour Cells Following Treatment With Xentuzumab | -52.55 Percentage change of Phospho-S6+ cells |
Secondary
Median Delay in Surgery in Participants Who Had More Than 4 Doses of Xentuzumab (and Whose Surgery Was Delayed by Factors Other Than Trial Treatment)
All participants who had more than 4 doses of xentuzumab were considered to have had their surgery delayed by factors other than trial treatment. Per protocol, all participants who had delayed surgery received additional weekly doses of xentuzumab. Reason for delay was not recorded as part of the study dataset. This endpoint was a measure of feasibility of the treatment schedule in the pre-operative setting.
Time frame: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.
Population: Number of participants who had more than 4 Doses of xentuzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xentuzumab | Median Delay in Surgery in Participants Who Had More Than 4 Doses of Xentuzumab (and Whose Surgery Was Delayed by Factors Other Than Trial Treatment) | 2 weeks |
Secondary
Number of Participants Who Had at Least 4 Doses of Xentuzumab and Proceeded to Have Surgery Per the Protocol Schedule
This endpoint was a measure of feasibility of the treatment schedule in the pre-operative setting.
Time frame: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.
Population: Total number of participants who had at least 4 doses of xentuzumab. Excludes one registered patient who progressed prior to surgery and came off trial.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Xentuzumab | Number of Participants Who Had at Least 4 Doses of Xentuzumab and Proceeded to Have Surgery Per the Protocol Schedule | Surgery performed on schedule | 26 Participants |
| Xentuzumab | Number of Participants Who Had at Least 4 Doses of Xentuzumab and Proceeded to Have Surgery Per the Protocol Schedule | Surgery delayed by trial treatment | 0 Participants |
Secondary
Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial
This endpoint was designed to assess safety and tolerability of xentuzumab administered in the pre-prostatectomy setting. AEs & SAEs were graded using CTCAE v5.0, with higher grades considered to be worse outcomes.
Time frame: From consent at week -1 to the end of study visit at up to 19 weeks
Population: All participants registered to take part in the WINGMEN trial. All participants received xentuzumab.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Xentuzumab | Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial | Any AE, Highest Grade 1 or 2 (CTCAE v5.0) | 23 Participants |
| Xentuzumab | Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial | Any AE, Highest Grade 3,4,5 (CTCAE v5.0) | 1 Participants |
| Xentuzumab | Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial | Any SAE, Highest Grade 1 or 2 (CTCAE v5.0) | 0 Participants |
| Xentuzumab | Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial | Any SAE, Highest Grade 3,4,5 (CTCAE v5.0) | 0 Participants |
| Xentuzumab | Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial | No AEs or SAEs reported | 3 Participants |
Secondary
Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial
Number of patients with any TRAE from the time of consent to the end of study visit. TRAEs are AEs that are investigator-determined to be definitely, probably or possibly related to treatment with xentuzumab and graded using CTCAE v5.0, with higher grades considered to be worse outcomes. This endpoint was designed to assess safety and tolerability of xentuzumab administered in the pre-prostatectomy setting.
Time frame: From consent at week -1 to the end of study visit at up to 19 weeks
Population: All participants registered to take part in the WINGMEN trial. All participants received xentuzumab.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Xentuzumab | Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial | Any TRAE, Highest Grade 1 or 2 (CTCAE v5.0) | 17 Participants |
| Xentuzumab | Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial | Any TRAE, Highest Grade 3,4,5 (CTCAE v5.0) | 0 Participants |
| Xentuzumab | Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial | No TRAE | 10 Participants |