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Health Condition(s) or Problem
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Prostate Adenocarcinoma
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Lay Summary
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Added as of 23/01/2013:
Prostate cancers depend upon the male hormone testosterone for their growth. Lowering testosterone levels (either by removing all or part of both testes, or by giving anti-hormone treatment) slows the growth of prostate cancers. This type of treatment is called hormone treatment and is often used when prostate cancers have spread outside the prostate gland. Although hormone treatment is usually successful at stopping the cancer growing for a period of time, the cancer will begin to grow again in most men.
There are increasing numbers of treatments available for advanced prostate cancer. These treatments are usually used in prostate cancer when hormone treatment is no longer effective and the cancer has started to grow again. The aim of this trial, which is called STAMPEDE, is to assess f of these treatments, given earlier in the course of the disease in combination with hormone treatment.
The treatments assessed during the trial are:
Zoledronic acid, Docetaxel, Celecoxib (No longer recruiting patients for this arm after interim analysis failed to show sufficient activity), Abiraterone and/or radiotherapy to the prostate.
The trial information can also be found at the following MRC CTU web page: http://http://stampedetrial.org/ (from UKCRN Portfolio)
Additional lay summaries...
http://www.cancerhelp.org.uk/trials/a-trial-looking-at-hormone-therapy-with-zoledronic-acid-docetaxel-or-celecoxib-for-prostate-cancer (from ISRCTN)
Prostate cancers depend upon the male hormone testosterone for their growth. Lowering
testosterone levels (either by removing all or part of both testes, or by giving
anti-hormone treatment) slows the growth of prostate cancers. This type of treatment is
called hormone treatment and is often used when prostate cancers have spread outside of the
prostate gland. Although hormone treatment is usually successful at stopping the cancer
growing for a period of time, the cancer will begin to grow again in most men.
There are increasing numbers of treatments available for advanced prostate cancer. These
treatments are usually used in prostate cancer when hormone treatment is no longer effective
and the cancer has started to grow again. The aim of this trial, which is called STAMPEDE,
is to assess five of these treatments, given earlier in the course of the disease in
combination with hormone treatment.
The treatments assessed during the trial are:
1. Zoledronic acid: Prostate cancer cells can spread to bones and weaken them. Zoledronic
acid is a drug that reduces bone destruction and hardens bones. This may make them more
resistant to attack by cancer cells.
2. Docetaxel: A drug that stops cells replicating, Docetaxel is currently being used to
treat a range of cancers including lung, breast and ovarian cancer as well as prostate
cancer. Docetaxel is already known to prolong survival in men with relapsed metastatic
prostate cancer.
3. Celecoxib: An aspirin-like drug that is used to treat arthritis. Celecoxib slows down
the growth of cancer cells in the laboratory. We wished to see if it had the same
effect on cancer cells in patients. Recruitment to new patients for the evaluation of
this drug is finished as a pre-planned interim analysis failed to demonstrate
sufficient activity.
4. Abiraterone (included from protocol version 8.0): An inhibitor of steroid hormone
synthesis that blocks prostate cancer cells from generating their own male hormones.
This is thought to be a major way in which prostate cancer cells resume growth
following castration based therapies. This agent is given along with prednisolone and
is already known to prolong survival when given to men following failure of docetaxel
chemotherapy.
5. Prostate radiotherapy (included from protocol version 9.0): Treatment with high-energy
x-rays targeted to the prostate gland. This treatment is now mandatory for patients
with cancer that is confined to the prostate gland as large trials have shown it
improves survival times. We are interested in whether we should give radiotherapy to
the prostate if the cancer has already spread.
STAMPEDE will look at the effect of combining one or two of the treatments described above
with hormone treatment. A computer program will be used to allocate which treatment the
patient receives, using a chance process. The trial will look at the effects of the combined
treatments on quality of life and find out whether the new treatment combinations increase
the time when the cancer is not growing and ultimately results in patients living longer.
The study will also look at which treatment provides the greater value for money for the
health service. More than 5,000 patients will join the trial with answers becoming available
over 7 to 12 years.
(from ClinicalTrials.gov)
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Who can enter the trial
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Current inclusion criteria as of 23/01/2013:
Patients must fulfil both of the criteria in Section 1 or one criterion in Section 2 or at least one criteria in Section 3. Additionally, all patients must fulfil the criteria in Section 4.
1 HIGH-RISK NEWLY DIAGNOSED NON-METASTATIC NODE-NEGATIVE DISEASE - Both:
1.1. At least two of: Stage T3/4, PSA=40ng/ml or Gleason sum score 8-10
1.2. Intention to treat with radical radiotherapy (unless there is a contra-indication; exemption can sought in advance of consent, after discussion with MRC CTU)
OR
2. NEWLY DIAGNOSED METASTATIC OR NODE-POSITIVE DISEASE - At least one of:
2.1. Stage Tany N+ M0
2.2. Stage Tany Nany M+
OR
3. PREVIOUSLY TREATED WITH RADICAL SURGERY AND/OR RADIOTHERAPY, NOW RELAPSING - At least one of:
3.1. PSA =4ng/ml and rising with doubling time less than 6 months
3.2. PSA =20ng/ml
3.3. N+
3.4. M+
AND
4. FOR ALL PATIENTS
4.1. Histologically confirmed prostate adenocarcinoma
4.2. Intention to treat with long-term androgen deprivation therapy
4.3. Fit for all protocol treatment2 and follow-up, WHO performance status 0-23
4.4 Have completed the appropriate investigations prior to randomisation
4.5. Adequate haematological function: neutrophil count >1.5x109/l and platelets >100x109/l
4.6. Estimated creatinine clearance >30ml/min
4.7. Serum potassium =3.5mmol/L
4.8. Written informed consent
4.9. Willing and expected to comply with follow-up schedule
4.10. Using effective contraceptive method if applicable
Previous inclusion criteria until 23/01/2013
Patients must fulfil one of the inclusion criteria in section one or one of the inclusion criteria in section two. Additionally, all patients must fulfil the inclusion criteria in section three:
Section one - high risk newly diagnosed patients must fulfil one of the following criteria:
1. Stage T3/4 N0 M0 histologically confirmed prostate adenocarcinoma with Prostate Specific Antigen (PSA) = 40 ng/ml or Gleason sum score eight to ten
2. Stage Tany N + M0 or Tany Nany M + histologically confirmed prostate adenocarcinoma
3. Multiple sclerotic bone metastases with a PSA = 100 ng/ml
Section two - patients with histologically confirmed prostate adenocarcinoma previously treated with radical surgery or radiotherapy that are now relapsing. (Please note that prior hormone therapy for localised disease must have been completed 12 months previously, have been no longer than 12 months in duration and given as adjuvant or neoadjuvant therap:
1. PSA = 4 ng/ml and rising with doubling time less than six months
2. PSA = 20 ng/ml
Section three - for all patients:
1. Intention to treat with long-term androgen suppression
2. Fit for all protocol treatment and follow-up, World Health Organisation (WHO) performance status zero to two
3. Have completed the appropriate investigations prior to randomisation
4. Adequate haematological function: neutrophil count more than 1.5 x 10^9 l and platelets more than 100 x 10^9 l
5. Adequate renal function: Serum creatinine less than 1.5 Upper Limit of Normal (ULN)
6. Adequate liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 1.5 ULN, bilirubin less than ULN
7. Normal testosterone level prior to treatment
8. Written informed consent
9. Willing and expected to comply with follow-up schedule
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Who cannot enter the trial
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Current exclusion criteria as of 23/01/2013:
1. Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in Section 4.1.3.
2. Metastatic brain disease or leptomeningeal disease
3. Abnormal liver functions consisting of any of the following:
? Serum bilirubin =1.5 x ULN (except for patients with Gilbert?s disease, for whom the upper limit of serum bilirubin is 51.3µmol/l or 3mg/dl)
? Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2.5 x ULN
4. Any other previous or current malignant disease which, in the judgement of the responsible physician, is likely to interfere with STAMPEDE treatment or assessment
5. Patients with active peptic ulceration, gastrointestinal bleeding, inflammatory bowel disease
6. Symptomatic peripheral neuropathy grade ?2 (NCI CTC)5
7. Any surgery (e.g. TURP) performed within the past 4 weeks
8. Patients with significant cardiovascular disease such that, in the investigator's opinion, the patient is unfit for any of the study treatments. This might include:
? Severe/unstable angina
? Myocardial infarction less than 6 months prior to randomisation
? Arterial thrombotic events less than 6 months prior to randomisation
? Clinically significant cardiac failure requiring treatment (NYHA II-IV)6
? Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 2 years prior to randomisation
? Patients with uncontrolled hypertension defined as systolic BP greater or equal than 160 mmHg or diastolic BP greater or equal than 95 mmHg
9. Patients who have been scheduled to have major dental extractions within the next 2 years
10. Patients receiving treatment with drugs known to induce CYP3A4 (including phenytoin, carbamazepine, Phenobarbital)7
11. Prior exposure to abiraterone
12. Prior chemotherapy for prostate cancer
13. Prior therapy with zoledronic acid other than short-term treatment for hypercalcaemia
14. Prior exposure to policy of long-term hormone therapy before randomisation (unless as described in Section 4.4.2 of the protocol)
SELECTION CRITERIA FOR COMPARISON OF RESEARCH (M1) RT FOR METASTATIC DISEASE
All patients meeting criteria above are eligible for the trial, but not all can be allocated to the research (M1) radiotherapy arm. The selection criteria for this ?RT to the prostate? comparison are:
1. Newly diagnosed prostate cancer
2. Demonstrable M1 disease
3. No contraindication to radiotherapy e.g. no previous pelvic radiotherapy,
4. No previous radical prostatectomy
Patients meeting these criteria will have a chance to be allocated to Arms A and H.
Previous exclusion criteria until 23/01/2013:
1. Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in section two
2. Metastatic brain disease or leptomeningeal disease
3. Any other previous or current malignant disease which, in the judgement of the responsible physician, is likely to interfere with STAMPEDE treatment or assessment
4. Symptomatic peripheral neuropathy grade two (National Cancer Institute Common Toxicity Criteria [NCI CTC])
5. Any surgery (e.g. transurethral resection of the prostate [TURP]) performed within the past four weeks
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What will happen
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Current interventions as of 23/01/2013:
Arm A = Androgen deprivation therapy (ADT) - control
Arm B = ADT + zoledronic acid
Arm C = ADT + docetaxel
Arm D = ADT + celecoxib
Arm E = ADT + zoledronic acid + docetaxel (NOW CLOSED)
Arm F = ADT + zoledronic acid + celecoxib (NOW CLOSED)
Arm G = ADT + abiraterone (included from protocol version 8.0):
Arm H = ADT + radiotherapy to the prostate (included from protocol version 9.0)
1. Zoledronic acid: Prostate cancer cells can spread to bones and weaken them. Zoledronic acid is a drug that reduces bone destruction and hardens bones. This may make them more resistant to attack by cancer cells.
2. Docetaxel: A drug that stops cells replicating that is currently being used to treat a range of cancers including lung, breast and ovarian cancer as well as prostate cancer. Docetaxel prolongs survival in men with relapsed metastatic prostate cancer.
3. Celecoxib: An aspirin-like drug that is used to treat arthritis. It slows down the growth of cancer cells in the laboratory. We wished to see if it had the same effect on cancer cells in patients. Recruitment to new patients for the evaluation of this drug is finished as a planned interim analysis failed to demonstrate sufficient activity.
4. Abiraterone (included from protocol version 8.0): An inhibitor of steroid hormone synthesis that blocks prostate cancer cells from generating their own male hormones. This is thought to be a major way in which prostate cancer cells resume growth following castration based therapies. The agent prolongs survival when given to men following failure of docetaxel chemotherapy.
5. Prostate radiotherapy (included from protocol version 9.0): treatment with high-energy x-rays targeted to the prostate gland. This treatment is now mandatory for patients with cancer that is confined to the prostate gland as large trials have shown it improves survival times. We are not certain whether we should give radiotherapy to the prostate if the cancer has already spread.
Previous interventions until 23/01/2013:
Patients will be randomised to the control arm (Arm A) or one of the five investigational arms. All patients will receive androgen suppression (AS) to
castration level. The method of AS is a local choice but must be specified for each patient prior to randomisation. All trial treatments should commence as soon as practically possible after randomisation. Patients
having a bilateral orchidectomy should commence any additional treatment within four weeks of the operation unless there is a strong clinical reason not
to do so.
Arm A = Androgen suppression (AS) - control
Arm B = AS + zoledronic acid
Arm C = AS + docetaxel
Arm D = AS + celecoxib
Arm E = AS + zoledronic acid + docetaxel
Arm F = AS + zoledronic acid + celecoxib
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Primary aim
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Added as of 11/09/2008:
Pilot phase: Safety
Efficacy Stage I-III: Failure-free survival (FFS)
Efficacy Stage IV: Overall survival
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Secondary Aim
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Added as of 11/09/2008:
Pilot phase:
1. Feasibility
Efficacy Stage I-III:
2. Overall survival (OS)
3. Toxicity
4. Skeletal related events
Efficacy Stage IV:
1. Quality of life
2. Cost effectiveness
3. Failure-free survival?
4. Toxicity
5. Skeletal related events
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Participant Information Sheet
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Patient information can be found at: http://www.stampedetrial.org
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Website
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http://www.stampedetrial.org
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Recruitment Status
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Recruiting
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Nation
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England
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Location
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Birmingham
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