Prostatic NeoplasmsPhase 2NCT00817739
Intermittent Hormonal Therapy With Leuprorelin and Flutamide in the Treatment of Stage D2 or TxNxM1b,c
A Phase 2 study testing Leuprorelin and Flutamide in people with Prostatic Neoplasms, run by Takeda.
Trial summary
This study is aimed at evaluating the effects of intermittent hormonal treatment with complete androgen suppression (Leuprorelin 3.75 milligram [mg] sustained release [SR] and Flutamide) in patients presenting with stage D2 or Tx Nx M1 ≠ M1a metastatic prostrate cancer, with a prostate specific antigen (PSA) level… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Leuprorelin and Flutamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 341 participants
- Where
- No sites listed yet
- Study dates
- Dec 1996to Dec 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic cancer of the prostate (stage D2 or Tx Nx M1 ≠ M1a) with measurable bone or visceral (lung, liver, etc.) metastases (radiographic conformation was necessary in the event of a questionable bone scan detection in conjunction with only slightly elevated PSA levels [at least 20 ng/mL or less than or equal to 50 ng/mL]). The prostatic carcinoma could have been diagnosed at an earlier stage and treated without castration.
- Metastatic cancer of the prostate requiring first-line therapy.
- Pre-assessment PSA 5-fold or higher than the standard level set by the central laboratory, that is, PSA greater than or equal to (≥) 20 ng/mL as quantitated by the Hybritech radioimmunoassay (normal is less than [<] 4 ng/mL).
- ECOG performance status of no more than 2.
- Normal testosterone levels according to the central laboratory standards.
- Aspartate transaminase (AST) and alanine transaminase (ALT) < 2.25-fold higher than the standard levels set by the central laboratory (except when liver metastases were present).
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- Anticipated life expectancy greater than 9 months.
- Written informed consent given to participate and collaborate in the study. Inclusion Criteria for Continuous or Intermittent Treatment Phase
- Subjects who meet the pre-assessment criteria and who has PSA < 4 ng/mL after 6 months of induction therapy.
Who cannot join
- Subject refuse to sign the informed consent form or is likely to be uncooperative or not to comply with the obligations set out in the study protocol.
- Subject has received prior hormonal (and neoadjuvant) treatment prompting medical castration (estrogens, hormone-releasing hormone agonists, androgens) or has undergone surgical castration.
- Subject has undergone bilateral suprarenalectomy or hypophysectomy.
- Subject had another cancer (except basiloma) with the past 5 years.
- Subject has serious unstable progressive disease (renal, hepatic, cardiovascular, psychological, etc).
- Subject is receiving or has received another experimental treatment within 3 months prior to inclusion.
- Exclusion Criteria for Continuous or Intermittent Treatment Phase
- -Subjects who met the pre-assessment criteria and who, after 6 months of induction therapy, had PSA ≥ 4 ng/mL and/or on-treatment signs of disease progression.
About this study
Official title: Intermittent Hormonal Therapy With Leuprorelin (3.75 mg SR) and Flutamide in the Treatment of Stage D2 or Tx Nx M1 ≠ M1a Metastatic Cancer of the Prostate
This study is aimed at evaluating the effects of intermittent hormonal treatment with complete androgen suppression (Leuprorelin 3.75 milligram [mg] sustained release [SR] and Flutamide) in patients presenting with stage D2 or Tx Nx M1 ≠ M1a metastatic prostrate cancer, with a prostate specific antigen (PSA) level 5-fold higher than normal (PSA greater than or equal to [≥] 20 nanogram per milliliter [ng/mL], as quantitated by the Hybritech radioimmunoassay) and with a subsequent decline to normal (PSA less than [<] 4 ng/mL) during the initial 6 months of induction treatment. The results will be compared with those obtained after continuous hormonal therapy with complete androgen suppression.
Read the detailed description
This is an open, comparative, randomized (1:1), multicenter, European (France, Germany, Czech Republic, Slovakia and Bulgaria), Phase 2B study on parallel groups of patients presenting with metastatic prostate cancer (stage D2 or Tx Nx M1 ≠ M1a), with a PSA level ≥ 5-fold higher than normal (that is PSA ≥ 20 ng/mL, as quantitated by the Hybritech radioimmunoassay) which return to normal within 6 months after the initiation of total androgen blockade therapy with leuprorelin 3.75 mg SR and flutamide. It will involve 314 preselected patients.
A minimum of 180 eligible patients are required for this study. Selected patients will be randomized centrally in two parallel groups at study entry. This phase 2B study will enable evaluation of a high number of patients by direct comparison with conventional administration. The study comprises of two therapeutic phases:
- A 6 month induction phase with complete androgen suppression by leuprorelin 3.75 mg SR and flutamide. This phase involves patients meeting the preselection criteria.
- A data processing run per complete androgen suppression according to two methods, continuous or intermittent, for the patients satisfying the criteria of selection of the study and which will thus be randomized.
The selected patients will be randomized in two parallel groups at the time of inclusion:
- Group A patients will receive a continuous complete androgen suppression therapy by leuprorelin 3.75mg SR and flutamide, until the appearance of signs of disease progression or study end.
- Group B patients will receive an intermittent complete androgen suppression therapy by leuprorelin 3.75 mg SR and flutamide, until the study end or the appearance of signs of disease progression under treatment.
Group A patients will be routinely followed-up on a 3-month basis until there are signs of disease progression. Group B patients (intermittent therapy) will be monitored every 3 months during on-treatment periods under the same conditions as described for group A.
The 3-month clinical follow-up will be same during off-treatment periods, but if PSA increases to ≥10 ng/mL the patient must be contacted to schedule a prompt special visit in order to reinstitute hormonal therapy. Subsequent visits will be scheduled on a 3-month basis from the time of the special visit. Special visits will be the same as routine consultations, except that the laboratory tests will not be redone.
When on-therapy tumor progression will be documented, every 6 months the investigators will note all treatments administered to patients until death (while specifying the cause of death).
- Conditions
- Prostatic Neoplasms
- Being tested
- Leuprorelin, Flutamide
- Keywords
- Drug therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeuprorelinDrug
Leuprorelin injection
FlutamideDrug
Flutamide tablets
| Study group | Role | What they receive |
|---|---|---|
| Continuous Therapy | Active comparator | Continuous complete androgen suppression therapy with leuprorelin 3.75 mg sustained release (SR), injection, subcutaneously once every 28 days and flutamide, 250 mg, tablet, orally thrice daily until there are signs of disease progression. Receives: Drug: Leuprorelin; Drug: Flutamide |
| Intermittent therapy | Experimental | Intermittent complete androgen suppression therapy starting at randomization with interruption of treatment given in the induction period until PSA levels reach >=10 ng/mL or other signs of progression appear. Upon treatment resumption, leuproreline 3.75 mg SR, injection, subcutaneously once every 28 days and flutamide 250 mg, tablet, orally thrice daily, until PSA levels are <normal (that is, <4 ng/mL) and no signs of disease progression appear. The intermittent therapy will be continued similarly until the study end or the appearance of signs of disease progression under treatment. Receives: Drug: Leuprorelin; Drug: Flutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Overall Survival
Median Overall survival is defined as the number of days from date of inclusion to the date of death. For subjects who do not die, survival will be censored at the date of last contact.
Measured: Randomization (Month 6) up to Week 396 after randomization
Median Progression-Free Survival
Median Progression Free Survival=time from date of inclusion to date of first documentation of progressive disease (death, biological progression, clinical progression). Biological progression: date of the first PSA increase after the nadir and greater than or equal to (≥) 4 ng/mL under treatment. Clinical progression: date of appearance of the clinical sign of progression under treatment. Clinical signs of progression are: 1. Appearance of marked increase of bone pain or appearance of symptoms related to disease progression (example: liver, lungs, kidneys); 2. Alteration of general health conditions related to disease progression (decrease of at least 2 degrees in the European Organization for Research and Treatment of Cancer (ECOG) performance status, weight loss of more than 10% since the last visit); 3. Anemia - drop in hemoglobin level of more than 2 gram per deciliter (g/dL) since the last visit (only if disease related).
Measured: Randomization (Month 6) up to Week 396 after randomization
Secondary outcomes (2)
European Organization for research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) - C30
EORTC QLQ-C30: includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions uses 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions uses 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; for the 5 functional scales and the global quality-of-life scale, a higher score represents a better level of functioning. For the symptom-oriented scales and items, a higher score corresponds to a higher level of symptoms.
Measured: Randomization (Month 6) up to Week 396 after randomization
Change from Baseline in Subjective Clinical Efficacy (Symptomatic)
Subjective clinical efficacy will be assessed using the Madsen Symptom Index and Lukacs' questionnaire. Symptoms will be assessed using visual analogue scale (VAS) in Lukacs questionnaire.
Measured: Randomization (Month 6) up to Week 396 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2009 (estimated)
- Study startDec 1996
- Primary completionSep 2005
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 341 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nicolas MOTTET, MD, Principal investigator, Clinique Mutualiste de Saint-Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817739
- Sponsor's protocol ID
- TAP IIb/95/022 - EC210
- Other IDs
- U1111-1169-6769
- Status last verified
- Jul 2015
- First submitted
- 5 Jan 2009
- Last updated
- 29 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intermittent Hormonal Therapy With Leuprorelin (3.75 mg SR) and Flutamide in the Treatment of Stage D2 or Tx Nx M1 ≠ M1a Metastatic Cancer of the Prostate
- ClinicalTrials.gov ID
- NCT00817739
- Acronym / sponsor ID
- TAP IIb/95/022 - EC210
- Conditions
- Prostatic Neoplasms
- Keywords
- Drug therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 341 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Dec 1996
- Primary completion
- Sep 2005 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 6 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is aimed at evaluating the effects of intermittent hormonal treatment with complete androgen suppression (Leuprorelin 3.75 milligram [mg] sustained release [SR] and Flutamide) in patients presenting with stage D2 or Tx Nx M1 ≠ M1a metastatic prostrate cancer, with a prostate specific antigen (PSA) level 5-fold higher than normal (PSA greater than or equal to [≥] 20 nanogram per milliliter [ng/mL], as quantitated by the Hybritech radioimmunoassay) and with a subsequent decline to normal (PSA less than [<] 4 ng/mL) during the initial 6 months of induction treatment. The results will be compared with those obtained after continuous hormonal therapy with complete androgen suppression.
Detailed description
This is an open, comparative, randomized (1:1), multicenter, European (France, Germany, Czech Republic, Slovakia and Bulgaria), Phase 2B study on parallel groups of patients presenting with metastatic prostate cancer (stage D2 or Tx Nx M1 ≠ M1a), with a PSA level ≥ 5-fold higher than normal (that is PSA ≥ 20 ng/mL, as quantitated by the Hybritech radioimmunoassay) which return to normal within 6 months after the initiation of total androgen blockade therapy with leuprorelin 3.75 mg SR and flutamide. It will involve 314 preselected patients.
A minimum of 180 eligible patients are required for this study. Selected patients will be randomized centrally in two parallel groups at study entry. This phase 2B study will enable evaluation of a high number of patients by direct comparison with conventional administration. The study comprises of two therapeutic phases:
- A 6 month induction phase with complete androgen suppression by leuprorelin 3.75 mg SR and flutamide. This phase involves patients meeting the preselection criteria.
- A data processing run per complete androgen suppression according to two methods, continuous or intermittent, for the patients satisfying the criteria of selection of the study and which will thus be randomized.
The selected patients will be randomized in two parallel groups at the time of inclusion:
- Group A patients will receive a continuous complete androgen suppression therapy by leuprorelin 3.75mg SR and flutamide, until the appearance of signs of disease progression or study end.
- Group B patients will receive an intermittent complete androgen suppression therapy by leuprorelin 3.75 mg SR and flutamide, until the study end or the appearance of signs of disease progression under treatment.
Group A patients will be routinely followed-up on a 3-month basis until there are signs of disease progression. Group B patients (intermittent therapy) will be monitored every 3 months during on-treatment periods under the same conditions as described for group A.
The 3-month clinical follow-up will be same during off-treatment periods, but if PSA increases to ≥10 ng/mL the patient must be contacted to schedule a prompt special visit in order to reinstitute hormonal therapy. Subsequent visits will be scheduled on a 3-month basis from the time of the special visit. Special visits will be the same as routine consultations, except that the laboratory tests will not be redone.
When on-therapy tumor progression will be documented, every 6 months the investigators will note all treatments administered to patients until death (while specifying the cause of death).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous Therapy | Active comparator | Drug: Leuprorelin, Drug: FlutamideContinuous complete androgen suppression therapy with leuprorelin 3.75 mg sustained release (SR), injection, subcutaneously once every 28 days and flutamide, 250 mg, tablet, orally thrice daily until there are signs of disease progression. |
| Intermittent therapy | Experimental | Drug: Leuprorelin, Drug: FlutamideIntermittent complete androgen suppression therapy starting at randomization with interruption of treatment given in the induction period until PSA levels reach >=10 ng/mL or other signs of progression appear. Upon treatment resumption, leuproreline 3.75 mg SR, injection, subcutaneously once every 28 days and flutamide 250 mg, tablet, orally thrice daily, until PSA levels are <normal (that is, <4 ng/mL) and no signs of disease progression appear. The intermittent therapy will be continued similarly until the study end or the appearance of signs of disease progression under treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed metastatic cancer of the prostate (stage D2 or Tx Nx M1 ≠ M1a) with measurable bone or visceral (lung, liver, etc.) metastases (radiographic conformation was necessary in the event of a questionable bone scan detection in conjunction with only slightly elevated PSA levels [at least 20 ng/mL or less than or equal to 50 ng/mL]). The prostatic carcinoma could have been diagnosed at an earlier stage and treated without castration.
- Metastatic cancer of the prostate requiring first-line therapy.
- Pre-assessment PSA 5-fold or higher than the standard level set by the central laboratory, that is, PSA greater than or equal to (≥) 20 ng/mL as quantitated by the Hybritech radioimmunoassay (normal is less than [<] 4 ng/mL).
- ECOG performance status of no more than 2.
- Normal testosterone levels according to the central laboratory standards.
Key exclusion criteria (8 listed)
- Subject refuse to sign the informed consent form or is likely to be uncooperative or not to comply with the obligations set out in the study protocol.
- Subject has received prior hormonal (and neoadjuvant) treatment prompting medical castration (estrogens, hormone-releasing hormone agonists, androgens) or has undergone surgical castration.
- Subject has undergone bilateral suprarenalectomy or hypophysectomy.
- Subject had another cancer (except basiloma) with the past 5 years.
- Subject has serious unstable progressive disease (renal, hepatic, cardiovascular, psychological, etc).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeuprorelinLeuprorelin injection | Drug | Continuous Therapy, Intermittent therapy |
| FlutamideFlutamide tablets | Drug | Continuous Therapy, Intermittent therapy |
Primary outcome
Median Overall Survival
Time frame: Randomization (Month 6) up to Week 396 after randomization
Median Overall survival is defined as the number of days from date of inclusion to the date of death. For subjects who do not die, survival will be censored at the date of last contact.
Median Progression-Free Survival
Time frame: Randomization (Month 6) up to Week 396 after randomization
Median Progression Free Survival=time from date of inclusion to date of first documentation of progressive disease (death, biological progression, clinical progression). Biological progression: date of the first PSA increase after the nadir and greater than or equal to (≥) 4 ng/mL under treatment. Clinical progression: date of appearance of the clinical sign of progression under treatment. Clinical signs of progression are: 1. Appearance of marked increase of bone pain or appearance of symptoms related to disease progression (example: liver, lungs, kidneys); 2. Alteration of general health conditions related to disease progression (decrease of at least 2 degrees in the European Organization for Research and Treatment of Cancer (ECOG) performance status, weight loss of more than 10% since the last visit); 3. Anemia - drop in hemoglobin level of more than 2 gram per deciliter (g/dL) since the last visit (only if disease related).
2 secondary outcomes
European Organization for research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) - C30
Time frame: Randomization (Month 6) up to Week 396 after randomization
Change from Baseline in Subjective Clinical Efficacy (Symptomatic)
Time frame: Randomization (Month 6) up to Week 396 after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas MOTTET, MD principal investigator
Clinique Mutualiste de Saint-Etienne
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leuprorelin and Flutamide in people with Prostatic Neoplasms, run by Takeda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Overall Survival (time frame: Randomization (Month 6) up to Week 396 after randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2015; AzTrials last refreshed its copy on 8 Nov 2026.