Prostate CancerPhase 1/2NCT00861471
Docetaxel (Taxotere) and Imatinib Mesylate (Gleevec) in Hormone Refractory Prostate Cancer
A Phase 1/2 study testing Docetaxel and Imatinib Mesylate in people with Prostate Cancer and Prostatic Neoplasms, run by NYU Langone Health at 3 sites in United States.
Trial summary
This trial is designed to determine the proper doses of Docetaxel and Imatinib mesylate to be used to treat hormone refractory prostate cancer and to evaluate the safety and efficacy of the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Prostatic Neoplasms
- What is being tested?
- Docetaxel and Imatinib Mesylate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2005to May 2010
- Phase
- Phase 1/2
- 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
- Patients at least 18 years of age.
- Histologically documented diagnosis of adenocarcinoma of prostate gland
- Patients must have hormone refractory prostate cancer having progressed after at least two prior hormonal manipulations with documented castrate levels of testosterone (<50 ng/dl). PSA ≥ 5 ng/ml
- Patients must have hormone-refractory prostate carcinoma as evidenced by PSA progression, with or without evidence of measurable disease, or evaluable disease by a positive bone scan. PSA progression is defined as > 25% increase in 2 consecutive tests in which the first increase in PSA should occur a minimum of 1 week from the reference value and this increase in PSA should be confirmed and ≥ 5 ng/ml
- Eligible patients will have been treated with at least two prior hormonal manipulations including androgen deprivation and may have received one prior chemotherapy regimen.
- Any chemotherapy, major surgery, or irradiation must have been completed at least 3 weeks prior to starting study drugs. Patient must have recovered from clinically significant toxicities incurred as a result of previous therapy except nail dystrophy, alopecia, grade 1 peripheral neuropathy, or radiation therapy induced affects (i.e., impotence or incontinence)
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- No recent prior flutamide (Eulexin) use within the past 4 weeks, prior bicalutamide (Casodex) use within the past 6 weeks, or prior nilutamide (Nilandron) use within the past 6 weeks.
- Performance status 0,1, 2 (Eastern Cooperative Oncology Group performance status scale)
- Adequate end organ function, defined as the following:
- total bilirubin < 1.5 x upper limit of Normal (ULN)
- Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) < 2.5 x ULN
- creatinine < 1.5 x ULN
- Absolute Neutrophil count (ANC) > 1.5 x 10^9/L
- platelets > 100 x 10^9/L
- Written, voluntary informed consent.
- Patients must have been and continue to be on androgen deprivation therapy with a Luteinizing hormone-releasing hormone (LHRH) agonist or antagonist during study participation except for patients who had orchiectomy.
- Patients on secondary hormonal manipulation with ketoconazole and hydrocortisone who discontinued LHRH therapy must be switched to single agent LHRH analogue therapy unless they had orchiectomy.
- Patients being treated with Zometa prior to the initiation of the study will be permitted to continue with Zometa while on the study.
Who cannot join
- Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patient with untreated brain metastasis or cord compression. However, patients with treated spinal cord compression or central nervous system (CNS) metastases that have been stable are eligible.
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
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- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry, unless the disease is rapidly progressing.
- Patient previously received radiotherapy to at least 25 % of the bone marrow
- Patient had a major surgery within 2 weeks prior to study entry.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- If the patient is taking steroids for prostate cancer, then the patient is ineligible for this study. If the patient is taking steroids for conditions other than prostate cancer, the patient is eligible provided that the reasons for use and dosage are documented. The investigator is urged to discuss this issue with the Study Principal Investigator for any clarification.
- No therapeutic anticoagulation with warfarin (e.g. Coumadin® or Coumadine®) will be permitted in patients participating in this study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Bellevue Hospital
New York, New York, 10016
NYU Clinical Cancer Center
New York, New York, 10016
NYU Tisch Hospital
New York, New York, 10016
About this study
Official title: Phase I/II, Open Label Study of Sequential Taxotere® (Docetaxel) and Gleevec® (Imatinib Mesylate) in Hormone Refractory Prostate Cancer
This trial is designed to determine the proper doses of Docetaxel and Imatinib mesylate to be used to treat hormone refractory prostate cancer and to evaluate the safety and efficacy of the treatment.
Read the detailed description
Androgen-independent prostate cancer is the second most common cause of cancer death in men. These patients have limited treatment options. Docetaxel(Taxotere) is the single most active agent for the treatment of hormone refractory prostate cancer. Phase II clinical trials including docetaxel combinations with other microtubule inhibitors have shown 60-70% prostate specific antigen (PSA) declines greater than 50% and 30-40% measurable disease responses. However, the duration of response is limited to roughly 22 weeks. Combinations with new agents are needed to increase the rate and duration of response over existing docetaxel containing combinations.
The platelet derived growth factor receptor(PDGFR)and platelet derived growth factor (PDGF) A are frequently expressed (80%) in primary and bone marrow metastasis of human prostate cancer (PC). Recent experimental evidence suggests that activation of PDGFR/PDGF can be oncogenic in the development and/or progression of PC. There is also evidence that PC cells that express PDGF promote PDGFR expression in endothelial cells and neo- angiogenesis. Together, these experimental evidence supports that inhibition of PDGFR may be of therapeutic benefit to advanced prostate cancer patients.
Gleevec (Imatinib mesylate ) is a potent inhibitor of PDGFR. Consistent with these observations, treatment with Gleevec in an experimental prostate cancer mouse model was better than paclitaxel alone in reducing bone metastasis but the antitumor effect was strongest with the combination of both. In a phase I study of heavily pretreated hormone refractory PC patients, Gleevec 600 mg/daily lead-in for 30 days followed by Gleevec 600 mg/daily with Paclitaxel 30mg/m2 weekly x4 weeks every 6 weeks induced a >50% PSA decline in 7% and 38% of patients respectively with acceptable toxicity. These observations suggested that this combination merits further investigation.
With high-dose docetaxel (70mg/m^2) being the single most active agent in hormone refractory prostate cancer and no data existing in the use of high-docetaxel with Gleevec, a phase I/II study to determine the maximum tolerated dose (MTD) of the combination and optimum dose for a phase II trial is warranted.
Gleevec is expected to affect the activation status of sensitive receptor tyrosine kinase targets and associated signaling effectors in the tumor cells and the neovasculature. However, it is not fully established to what extent alterations of the target and /or other molecules in the signaling pathway are essential for Gleevec's antitumor activity in prostate cancer patients. It is also unknown whether preexisting molecular changes in the prostate tumors of individual patients could affect Gleevec's activity even in the presence of the targets. Therefore, an assessment of the expression levels and/or presence of mutations of selected molecules in specimens of patients in clinical trials may contribute in various ways: 1. to understand the requirements to elicit or inhibit a response to the combination, 2. whether adding other targeted agents may improve response and/or 3. whether selection of patients that might benefit should be based on the tumor profile. Thus, whenever possible specimens form the primary and/or metastatic sites should be retrieved and/or obtained to perform these analyses.
- Conditions
- Prostate Cancer, Prostatic Neoplasms
- Being tested
- Docetaxel, Imatinib Mesylate
- Keywords
- hormone refractory prostate cancer, tyrosine kinase inhibitor, Gleevec, PSA, prostate specific antigen, growth factor receptor inhibitor, androgen independent
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Also called Taxotere
One treatment cycle is defined as 21 days.
Docetaxel: 70 mg/m^2 (60 mg/m^2 was tested in Phase I as well), Intravenous, every 21 days.
Imatinib MesylateDrug
Also called Gleevec
One treatment cycle is defined as 21 days.
Imatinib Mesylate: 24-36 hours after Docetaxel, 600 mg (400 mg was tested in Phase I as well), orally, daily x 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel +Gleevec | Experimental | Not described Receives: Drug: Docetaxel; Drug: Imatinib Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Prostate Specific Antigen (PSA) Response
PSA response is defined as a greater than or equal to a 50% decrease in PSA from the baseline without clinical or radiologic evidence of progression according to the Response Evaluation Criteria in Solid Tumors (RECIST). PSA concentration was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy.
Measured: up to 9 months
Secondary outcomes (4)
Percentage of Participants With Greater or Equal to 80% PSA Reduction From Baseline Without Clinical or Radiologic Evidence of Progression
PSA was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy.
Measured: up to 9 months
Percentage of Participants With Measurable Disease Response
Measurable disease response is defined as the number of participants whose best response is complete response or partial response over the number of patients with measurable desease according to the Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: up to 2 years
Time to PSA Progression
Time to PSA pregression is defined as the time at which therapy statred and ends when the PSA increased by 50% above the nadir confirmed on a second determination.
Measured: up to 2 years
Median Overall Survival Time
Overall survival time is the time from the start of therapy till death. Median overall survival reported here is the time when 50% of the participants are alive.
Measured: up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2009 (estimated)
- Study startMay 2005
- Primary completionMay 2010
- Study completionMay 2010
Why it stopped: due to slow accrual
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 NYU Langone HealthThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Anna Ferrari, MD, Principal investigator, New York University Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00861471
- Sponsor's protocol ID
- NYU 04-47 (H12554)
- Other IDs
- Novartis CSTI571BUS200
- Status last verified
- May 2016
- First submitted
- 12 Mar 2009
- Last updated
- 30 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II, Open Label Study of Sequential Taxotere® (Docetaxel) and Gleevec® (Imatinib Mesylate) in Hormone Refractory Prostate Cancer
- ClinicalTrials.gov ID
- NCT00861471
- Acronym / sponsor ID
- NYU 04-47 (H12554)
- Conditions
- Prostate Cancer, Prostatic Neoplasms
- Keywords
- hormone refractory prostate cancer, tyrosine kinase inhibitor, Gleevec, PSA, prostate specific antigen, growth factor receptor inhibitor, androgen independent
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to slow accrual
- Enrolment
- 24 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- May 2005
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 13 Mar 2009 (estimated)
- Results
- Posted 29 Jun 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is designed to determine the proper doses of Docetaxel and Imatinib mesylate to be used to treat hormone refractory prostate cancer and to evaluate the safety and efficacy of the treatment.
Detailed description
Androgen-independent prostate cancer is the second most common cause of cancer death in men. These patients have limited treatment options. Docetaxel(Taxotere) is the single most active agent for the treatment of hormone refractory prostate cancer. Phase II clinical trials including docetaxel combinations with other microtubule inhibitors have shown 60-70% prostate specific antigen (PSA) declines greater than 50% and 30-40% measurable disease responses. However, the duration of response is limited to roughly 22 weeks. Combinations with new agents are needed to increase the rate and duration of response over existing docetaxel containing combinations.
The platelet derived growth factor receptor(PDGFR)and platelet derived growth factor (PDGF) A are frequently expressed (80%) in primary and bone marrow metastasis of human prostate cancer (PC). Recent experimental evidence suggests that activation of PDGFR/PDGF can be oncogenic in the development and/or progression of PC. There is also evidence that PC cells that express PDGF promote PDGFR expression in endothelial cells and neo- angiogenesis. Together, these experimental evidence supports that inhibition of PDGFR may be of therapeutic benefit to advanced prostate cancer patients.
Gleevec (Imatinib mesylate ) is a potent inhibitor of PDGFR. Consistent with these observations, treatment with Gleevec in an experimental prostate cancer mouse model was better than paclitaxel alone in reducing bone metastasis but the antitumor effect was strongest with the combination of both. In a phase I study of heavily pretreated hormone refractory PC patients, Gleevec 600 mg/daily lead-in for 30 days followed by Gleevec 600 mg/daily with Paclitaxel 30mg/m2 weekly x4 weeks every 6 weeks induced a >50% PSA decline in 7% and 38% of patients respectively with acceptable toxicity. These observations suggested that this combination merits further investigation.
With high-dose docetaxel (70mg/m^2) being the single most active agent in hormone refractory prostate cancer and no data existing in the use of high-docetaxel with Gleevec, a phase I/II study to determine the maximum tolerated dose (MTD) of the combination and optimum dose for a phase II trial is warranted.
Gleevec is expected to affect the activation status of sensitive receptor tyrosine kinase targets and associated signaling effectors in the tumor cells and the neovasculature. However, it is not fully established to what extent alterations of the target and /or other molecules in the signaling pathway are essential for Gleevec's antitumor activity in prostate cancer patients. It is also unknown whether preexisting molecular changes in the prostate tumors of individual patients could affect Gleevec's activity even in the presence of the targets. Therefore, an assessment of the expression levels and/or presence of mutations of selected molecules in specimens of patients in clinical trials may contribute in various ways: 1. to understand the requirements to elicit or inhibit a response to the combination, 2. whether adding other targeted agents may improve response and/or 3. whether selection of patients that might benefit should be based on the tumor profile. Thus, whenever possible specimens form the primary and/or metastatic sites should be retrieved and/or obtained to perform these analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Docetaxel +Gleevec | Experimental | Drug: Docetaxel, Drug: Imatinib Mesylate |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients at least 18 years of age.
- Histologically documented diagnosis of adenocarcinoma of prostate gland
- Patients must have hormone refractory prostate cancer having progressed after at least two prior hormonal manipulations with documented castrate levels of testosterone (<50 ng/dl). PSA ≥ 5 ng/ml
- Patients must have hormone-refractory prostate carcinoma as evidenced by PSA progression, with or without evidence of measurable disease, or evaluable disease by a positive bone scan. PSA progression is defined as > 25% increase in 2 consecutive tests in which the first increase in PSA should occur a minimum of 1 week from the reference value and this increase in PSA should be confirmed and ≥ 5 ng/ml
- Eligible patients will have been treated with at least two prior hormonal manipulations including androgen deprivation and may have received one prior chemotherapy regimen.
Key exclusion criteria (13 listed)
- Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patient with untreated brain metastasis or cord compression. However, patients with treated spinal cord compression or central nervous system (CNS) metastases that have been stable are eligible.
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 |
|---|---|---|
| DocetaxelAlso: TaxotereOne treatment cycle is defined as 21 days. Docetaxel: 70 mg/m^2 (60 mg/m^2 was tested in Phase I as well), Intravenous, every 21 days. | Drug | Docetaxel +Gleevec |
| Imatinib MesylateAlso: GleevecOne treatment cycle is defined as 21 days. Imatinib Mesylate: 24-36 hours after Docetaxel, 600 mg (400 mg was tested in Phase I as well), orally, daily x 14 days. | Drug | Docetaxel +Gleevec |
Primary outcome
Percentage of Participants With Prostate Specific Antigen (PSA) Response
Time frame: up to 9 months
PSA response is defined as a greater than or equal to a 50% decrease in PSA from the baseline without clinical or radiologic evidence of progression according to the Response Evaluation Criteria in Solid Tumors (RECIST). PSA concentration was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy.
4 secondary outcomes
Percentage of Participants With Greater or Equal to 80% PSA Reduction From Baseline Without Clinical or Radiologic Evidence of Progression
Time frame: up to 9 months
Percentage of Participants With Measurable Disease Response
Time frame: up to 2 years
Time to PSA Progression
Time frame: up to 2 years
Median Overall Survival Time
Time frame: up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Anna Ferrari, MD principal investigator
New York University Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Docetaxel and Imatinib Mesylate in people with Prostate Cancer and Prostatic Neoplasms, run by NYU Langone Health at 3 sites 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 18 inclusion and 13 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: stopped early, as of the sponsor's last update on 30 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 29 Jun 2011). 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 Participants With Prostate Specific Antigen (PSA) Response (time frame: up to 9 months). 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 30 Jun 2016.