MRC Clinical Trials Unit at UCL
90 High Holborn
a. My patient’s pre-hormone therapy PSA was taken over 6 months ago, can they still enter the trial?
Unfortunately, no. We require a pre-hormone therapy PSA test within 6 months prior to randomisation and do not offer waivers. It may be possible to obtain these from the GP surgery or referring centre.
b. How many weeks before randomisation is a chest x-ray valid for the stampede trial?
The imaging for eligibility must be the latest available scan that reflects the patient’s current disease status.
c. My patient's HbA1c is 48mmol, can you confirm if it needs to be below 48 mmol or whether he is eligible with this reading?
The diagnostic criteria for diabetes is a HbA1c level of 48mmol/mol (6.5%) or over, as defined by the WHO. To be eligible for the metformin comparison all participants must be confirmed to not to have diabetes, so the HbA1c must 47mmol/mol or less. Please note steroid induced diabetes is a contraindication to join the metformin comparison. All participants must have a normal HbA1c prior to randomisation. However if the HbA1c is 48 or higher it is still possible to join the transdermal oestradiol comparison and be randomised between arm A and L.
d. Is it possible to participate in STAMPEDE when a resident of another country?
We run the STAMPEDE trial in over 120 hospital sites in the UK and a few centres in Switzerland. We require that patients are able attend to regular clinics for them to be monitored whilst on trial. This may render most people outside of UK and Switzerland ineligible but if the attendance requirement can be met, patients partially resident overseas can participate. The full list of eligibility criteria can be found on the patient information tab of the STAMPEDE website and in the protocol.
e. My patient can't read or write, can they still take part in STAMPEDE?
As long as they have capacity to do so and understand all the information about screening and trial procedures, informed consent can be taken.
Documentation for the consent process must include all of the following based on principles outlined in ICH GCP:
- How consent was obtained and who was present to witness it
- If verbal consent is obtained this must be documented and evidenced by the participant by marking that they indicates their consent (fingerprint or other mark-marking)
- Someone independent will need to be present as a witness, for example, another research nurse who does not work on the trial or if the participant brings a friend or relative to the appointment.
f. Is my patient eligible based on his alcohol intake?
The reference safety information for metformin advises against metformin use in individuals with excessive alcohol intake as this is a risk factor for lactic acidosis. Reasonable alcohol intake is safe. We would advise against randomising patients with alcohol dependency.
g. Question related to eligibility based on ‘general exclusion criteria VI’ – Patients with significant cardiovascular disease:
It is the decision of the treating clinician to determine whether the patient would be able to tolerate STAMPEDE study drug based on cardiovascular history and current cardiac function. The protocol requires the functional impact of cardiac disease to be assessed according to the New York Heart Association (NYHA) classification. Significant cardiac disease is defined as NYHA class 2 or more so to be eligible for STAMPEDE participants must meet the criteria for class 1. This states that ordinary physical activity does not cause fatigue, breathlessness or palpitations. See the appendices for full details of the NYHA criteria.
h. Is a Gleason score is required for study entry?
Gleason score is required to determine eligibility for patients with non-metastatic node-negative prostate cancer. If the participant has prostate cancer involving lymph nodes or distant metastases Gleason score is not required for entry into STAMPEDE.
i. My patient has ‘white coat syndrome’, can he obtain his blood pressure reading for eligibility at home?
Yes, self-monitoring of blood pressure is encouraged and investigators should review records and record the average value in the medical notes and use this to determine eligibility. Regular monitoring of blood pressure is required whilst receiving treatment and all blood pressure readings reported should be considered representative as judged by the investigator. It is accepted that clinic readings may not be the most accurate but alternative values within protocol specified limits obtained by the patient or GP must be documented in the medical notes.
j. Both the CT and MRI of the spine show bony metastases. Do we need to do a bone scan?
All patients entering STAMPEDE must have had a complete assessment of the skeleton to assess for the presence and burden of bone metastases. The acceptable forms of imaging are a nuclear medicine bone scan, whole body MRI or the CT component of a PET scan. Therefore in this example, unless the MRI was whole body, an additional bone scan would be required.
k. Is it possible for my patient to be entered although they have had over the maximum number of weeks on hormone therapy before randomisation?
No, unfortunately STAMPEDE offers no waivers and the prior duration of hormone therapy is strictly enforced. The below table summarises the maximum permitted durations for each comparison:
l. Why are patients with relapsed disease considered ineligible if they have had more than 12 months hormone therapy when they were first treated for localised disease?
For patients with relapsing disease, the STAMPEDE protocol requires that they have only received a limited amount of prior hormone therapy. This is because STAMPEDE aims to evaluate treatments in “hormone-naïve” prostate cancer. Therefore the eligibility criteria limits the prior hormone therapy to 12 months duration and it must have been completed at least 12 months previously.
m. What drugs are contra-indicated for patients receiving transdermal oestradiol?
Transdermal oestradiol is contraindicated with tamoxifen. See Section 6.3 for further details on concomitant medications.
n. What types of scans are acceptable imaging of the abdomen and pelvis?
Adequate cross sectional imaging is required to detect the presence of liver metastases and any pelvic or intra-abdominal nodal metastases e.g. para-aortic lymph nodes. Either a CT or MRI is acceptable. Protocols such as CT urograms may be acceptable providing the radiologist can report on the liver and all the required regional lymph nodes.
o. What types of scan are acceptable for bone imaging?
- Nuclear medicine bone scan
- Whole body MRI
- CT component of a PET scan e.g. whole body choline-PET-CT or PSMA
Please note, for trial purposes M1 disease will be defined using internationally agreed criteria, therefore M1 staging cannot be based solely on PET avid lesions. To be considered M1, the metastatic lesion must also be visible on standard imaging i.e. bone scan, CT or MRI.
p. Can my patient be considered for STAMPEDE even though he hasn’t had a prostate biopsy?
Yes, providing a biopsy of a disease site has been performed and confirms prostate cancer. The pathology report must state that the prostate cancer is predominantly adenocarcinoma. This histological diagnosis may be made from sampling any site of disease, prostate, lymph node or another metastatic site.
q. Can a patient with diet controlled diabetes be considered for randomisation to the metformin comparison?
No, only patients without any prior or current history of diabetes are eligible for randomisation to the metformin comparison. This includes all types of diabetes. Patients with diabetes may still be considered eligible for randomisation to arms A and L i.e. the transdermal oestradiol comparison.
r. Can I give my patient with oligometastatic disease radical RT to the prostate?
STAMPEDE Arm H results showed that patients with oligometastatic disease (as per the CHAARTED definition) had a better overall survival when treated with radical RT to the prostate, although this did not hold true for patients with a high metastatic burden. This also provides stronger evidence that patients with N+M0 disease will benefit from radical RT to the prostate and we encourage it to be considered in this setting. Currently radical RT to the prostate for patients with oligometastatic prostate cancer is not considered standard of care or protocol treatment in STAMPEDE, however we will be revising this is when we next update our protocol and open new arms.
In the meantime if you are enrolling a new patient and you feel it is in their best interests to have radical RT to the prostate please record the intention to treat with radical radiotherapy as you would for a patient that had non-metastatic disease on the radiotherapy detail form. The decision of whether to include radical RT to the prostate must be stated at randomisation as it is a stratification factor for the randomisation. Please refer to the protocol for the regimens used in the M1:RT comparison.
If the patient has already been randomised (prior to the release of the M1RT results) but you now feel it is in their best interests to receive radical RT to the prostate please also record this on the radiotherapy detail form. In addition please send a cover letter documenting change from decision at time of randomisation (not for RT) to RT on basis of new trial data. This ensures we are kept updated of all treatments participants are receiving.
Have another question or looking for more information? why not check out the STAMPEDE Training Suite for the training slides detailing information on STAMPEDE.
MRC Clinical Trials Unit at UCL