Prostate CancerNCT01084759
A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer
A study testing Testosterone injection and Etoposide in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
The objective of the study is to determine if men with evidence of progressive prostate cancer while on chronic androgen ablation of ≥ 1 year duration will exhibit a clinical response following administration of parenteral testosterone and oral etoposide. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Testosterone injection and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Oct 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Performance status ≤2
- Documented adenocarcinoma of the prostate with histologic confirmation
- Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist for ≥ 1 year)
- Documented castrate level of serum testosterone (<50 ng/dl)
- Evidence of rising PSA on two successive dates > 1 month apart
- Treatment with ≤ 2 prior chemotherapeutic regimens allowed
Show all 17Show fewer
- Treatment with ≤2 prior second line hormone therapies allowed.
- Prior treatment with ketoconazole is allowed.
- Patients must be withdrawn from antiandrogens for ≥ 6 weeks and have documented PSA increase after the 6 week withdrawal period.
- Patients with rising PSA only or ≤ 5 sites of asymptomatic bone metastases and < 10 total sites of disease including bone and soft tissue documented within 28 days of enrollment on trial.
- Patients will considered for repeat treatment with testosterone if they meet the following criteria:
- Had either PSA decline from baseline following treatment with testosterone or had return of PSA levels to pretreatment baseline once serum testosterone reached a castrate level.
- Must continue to meet inclusion/exclusion criteria as described above
- Must have been off testosterone therapy for ≥ 3 months
- Must have castrate level of serum testosterone
- Must have evidence of rising PSA on two occasions at least 2 weeks apart
- Are allowed to have had additional treatment with up to 2 additional hormonal therapies that include anti-androgens (e.g. flutamide, bicalutamide, nilutamide, enzalutamide), CYP17 inhibitors (e.g. ketoconazole, abiraterone acetate) or other investigational hormonal therapies.
Who cannot join
- Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
- Abnormal liver function (bilirubin, AST, ALT ≥ 2 x upper limit of normal)
- Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21205
About this study
The objective of the study is to determine if men with evidence of progressive prostate cancer while on chronic androgen ablation of ≥ 1 year duration will exhibit a clinical response following administration of parenteral testosterone and oral etoposide.
Treatment Plan: Eligible patients will continue on androgen ablative therapy with luteinizing hormone-releasing hormone (LHRH) agonist (i.e. Zoladex or Lupron) if not surgically castrated. Patients will receive intramuscular injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy). This dose was selected based on data demonstrating that it produces an initial supraphysiologic serum level of testosterone (i.e. > 3-5 times normal level) with eugonadal levels achieved at the end of two weeks. Beginning the day of the testosterone injection, patients will also receive oral etoposide 100 mg/day in divided doses (50 mg q 12h) x 14 days out of 28 days per cycle. After 3 months on therapy, patients will have repeat prostate specific antigen (PSA) and bone/computed tomography (CT) scans to establish the effect of combined testosterone and etoposide treatment on these parameters (i.e. "testosterone effect baseline"). Patients with sustained elevations in PSA ≥ 50% above pre-testosterone treatment PSA levels after the initial three months of testosterone and etoposide therapy will not receive continued therapy and will come off study. Patients with PSA levels less than the peak serum PSA level seen over the three month period (PSA decline) or patients with PSA ≤ 50% of pretreatment baseline will receive a second 3 month course of monthly testosterone and etoposide therapy until evidence of disease progression. Disease progression is defined as a PSA increase above the PSA level obtained after 3 months on testosterone treatment over two successive measurements 2 weeks apart or evidence of new lesions or progression on bone/CT scans compared to baseline studies. Patients who respond to initial treatment with testosterone and etoposide and then show signs of progression will have the option of retreatment with testosterone alone after a period of 3 months or greater off of the original therapy.
Read the detailed description
Based on our preclinical data, high levels of androgens can lead to significant growth suppressive effects in prostate cancer cells in vitro and in vivo. Mechanistic data in in vitro models suggests that this growth suppression may be due to the accumulation of androgen induced TOP2B mediated double strand breaks at AR target sites occurring after stimulation of prostate cancer cells with high levels of androgens. Provocatively, the number of double strand breaks was significantly increased (Figure 3 B) if the cells were treated with etoposide, an agent that leads to formation of double strand breaks at TOP2 target sites, concurrently with high-dose androgen stimulation. We hypothesize that co-administration of testosterone with etoposide could produce high levels of double strand breaks in prostate cancer cells, overwhelming DNA repair and survival mechanisms and leading to cancer cell death or growth arrest. To test whether this possibility holds promise for therapy of advanced prostate cancer, we propose the following clinical trial of parenteral testosterone therapy in combination with oral etoposide in men with evidence of progressive prostate cancer during chronic androgen ablation.
- Conditions
- Prostate Cancer
- Being tested
- Testosterone injection, Etoposide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone injectionDrug
Also called Testosterone Cypionate
Patients will receive an intramuscular gluteal injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy). This route and dose of testosterone was selected based on data demonstrating that it produces an initial supraphysiologic serum level of testosterone (i.e. > 3-5 times normal level) with eugonadal levels achieved at the end of two weeks.
EtoposideDrug
Also called Etopophos, Toposar
On the day of testosterone injection (i.e. day 1 of each cycle) patients will begin therapy with oral etoposide at a dose of 100 mg/day given in divided doses (one 50 mg etoposide capsule q 12 h) for 14 consecutive days. This dose was selected based on Phase II studies of the combination of oral estramustine and oral etoposide. In these trials, myelosuppression was observed when etoposide was given for 21 days out of a 28 day cycle. Therefore, to minimize toxicity, in this study etoposide will be administered for 14 days of a 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Etoposide and Testosterone | Experimental | Patients will receive an intramuscular gluteal injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy).On the day of testosterone injection (i.e. day 1 of each cycle) patients will begin therapy with oral etoposide at a dose of 100 mg/day given in divided doses (one 50 mg etoposide capsule q 12 h) for 14 consecutive days. Receives: Drug: Testosterone injection; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Completing at Least 3 Months of Therapy With a PSA Below Baseline.
Measured: 3 months
Time to PSA Progression
Time to a PSA increase above the PSA level obtained after 3 months on testosterone treatment over two successive measurements 2 weeks apart.
Measured: 2 years
Secondary outcomes (1)
Number of Participants With RECIST Response (i.e. Complete Response or Partial Response)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan or MRI. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Denmeade, MD, Principal investigator, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer CenterAlberto J Pacheco, BA, Study chair, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer CenterTing Wang, MS, Study director, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01084759
- Sponsor's protocol ID
- J09121, NA_00033419
- Status last verified
- Jan 2016
- First submitted
- 9 Mar 2010
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT01084759
- Acronym / sponsor ID
- J09121, NA_00033419
- Conditions
- Prostate Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 10 Mar 2010 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the study is to determine if men with evidence of progressive prostate cancer while on chronic androgen ablation of ≥ 1 year duration will exhibit a clinical response following administration of parenteral testosterone and oral etoposide.
Treatment Plan: Eligible patients will continue on androgen ablative therapy with luteinizing hormone-releasing hormone (LHRH) agonist (i.e. Zoladex or Lupron) if not surgically castrated. Patients will receive intramuscular injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy). This dose was selected based on data demonstrating that it produces an initial supraphysiologic serum level of testosterone (i.e. > 3-5 times normal level) with eugonadal levels achieved at the end of two weeks. Beginning the day of the testosterone injection, patients will also receive oral etoposide 100 mg/day in divided doses (50 mg q 12h) x 14 days out of 28 days per cycle. After 3 months on therapy, patients will have repeat prostate specific antigen (PSA) and bone/computed tomography (CT) scans to establish the effect of combined testosterone and etoposide treatment on these parameters (i.e. "testosterone effect baseline"). Patients with sustained elevations in PSA ≥ 50% above pre-testosterone treatment PSA levels after the initial three months of testosterone and etoposide therapy will not receive continued therapy and will come off study. Patients with PSA levels less than the peak serum PSA level seen over the three month period (PSA decline) or patients with PSA ≤ 50% of pretreatment baseline will receive a second 3 month course of monthly testosterone and etoposide therapy until evidence of disease progression. Disease progression is defined as a PSA increase above the PSA level obtained after 3 months on testosterone treatment over two successive measurements 2 weeks apart or evidence of new lesions or progression on bone/CT scans compared to baseline studies. Patients who respond to initial treatment with testosterone and etoposide and then show signs of progression will have the option of retreatment with testosterone alone after a period of 3 months or greater off of the original therapy.
Detailed description
Based on our preclinical data, high levels of androgens can lead to significant growth suppressive effects in prostate cancer cells in vitro and in vivo. Mechanistic data in in vitro models suggests that this growth suppression may be due to the accumulation of androgen induced TOP2B mediated double strand breaks at AR target sites occurring after stimulation of prostate cancer cells with high levels of androgens. Provocatively, the number of double strand breaks was significantly increased (Figure 3 B) if the cells were treated with etoposide, an agent that leads to formation of double strand breaks at TOP2 target sites, concurrently with high-dose androgen stimulation. We hypothesize that co-administration of testosterone with etoposide could produce high levels of double strand breaks in prostate cancer cells, overwhelming DNA repair and survival mechanisms and leading to cancer cell death or growth arrest. To test whether this possibility holds promise for therapy of advanced prostate cancer, we propose the following clinical trial of parenteral testosterone therapy in combination with oral etoposide in men with evidence of progressive prostate cancer during chronic androgen ablation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etoposide and Testosterone | Experimental | Drug: Testosterone injection, Drug: EtoposidePatients will receive an intramuscular gluteal injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy).On the day of testosterone injection (i.e. day 1 of each cycle) patients will begin therapy with oral etoposide at a dose of 100 mg/day given in divided doses (one 50 mg etoposide capsule q 12 h) for 14 consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Performance status ≤2
- Documented adenocarcinoma of the prostate with histologic confirmation
- Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist for ≥ 1 year)
- Documented castrate level of serum testosterone (<50 ng/dl)
- Evidence of rising PSA on two successive dates > 1 month apart
Key exclusion criteria (4 listed)
- Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
- Abnormal liver function (bilirubin, AST, ALT ≥ 2 x upper limit of normal)
- Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
- Inability to provide informed consent
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 |
|---|---|---|
| Testosterone injectionAlso: Testosterone CypionatePatients will receive an intramuscular gluteal injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy). This route and dose of testosterone was selected based on data demonstrating that it produces an initial supraphysiologic serum level of testosterone (i.e. > 3-5 times normal level) with eugonadal levels achieved at the end of two weeks. | Drug | Etoposide and Testosterone |
| EtoposideAlso: Etopophos, ToposarOn the day of testosterone injection (i.e. day 1 of each cycle) patients will begin therapy with oral etoposide at a dose of 100 mg/day given in divided doses (one 50 mg etoposide capsule q 12 h) for 14 consecutive days. This dose was selected based on Phase II studies of the combination of oral estramustine and oral etoposide. In these trials, myelosuppression was observed when etoposide was given for 21 days out of a 28 day cycle. Therefore, to minimize toxicity, in this study etoposide will be administered for 14 days of a 28 day cycle. | Drug | Etoposide and Testosterone |
Primary outcome
Percentage of Patients Completing at Least 3 Months of Therapy With a PSA Below Baseline.
Time frame: 3 months
Time to PSA Progression
Time frame: 2 years
Time to a PSA increase above the PSA level obtained after 3 months on testosterone treatment over two successive measurements 2 weeks apart.
1 secondary outcome
Number of Participants With RECIST Response (i.e. Complete Response or Partial Response)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Samuel Denmeade, MD principal investigator
Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
Alberto J Pacheco, BA study chair
Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
Ting Wang, MS study director
Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Testosterone injection and Etoposide in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
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 17 inclusion and 4 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 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Patients Completing at Least 3 Months of Therapy With a PSA Below Baseline. (time frame: 3 months). 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 9 May 2016.