Metastatic, Androgen Independent Prostate CancerPhase 1/2NCT00459186
The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
A Phase 1/2 study testing RAD001, Docetaxel and Prednisone in people with Metastatic, Androgen Independent Prostate Cancer and Prostate Cancer, run by Dana-Farber Cancer Institute at 5 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I). Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic, Androgen Independent Prostate Cancer, Prostate Cancer
- What is being tested?
- RAD001, Docetaxel and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 5 sitesUnited States
- Study dates
- Nov 2005to Dec 2012
- 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
- Adenocarcinoma of the prostate with radiographic evidence of metastatic disease.
- Willingness to undergo a baseline tumor biopsy.
- Castrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT) with evidence of progression on ADT. GnRH therapy will be continued for those on it at baseline
- Patient must have suspected tumor in an area that is safe to biopsy.
- Other prior hormonal interventions or experimental approaches are allowed. These therapies must have been discontinued for a minimum of 28 days with cancer progression.
- Prior or concurrent use of bisphosphonates is allowed.
Show all 10Show fewer
- One prior non-taxane chemotherapy allowed
- ≥ 3 weeks since major surgery; ≥ 4 weeks since radiotherapy; ≥ 8 weeks since prior strontium-89 or samarium 153
- Performance Status: ECOG 0 or 1
- ANC > 1,500/_l; platelets > 100,000/_l; total Bilirubin < upper limit of normal; AST and ALT < 3 x upper limits of normal; creatinine < 1.5 x upper limits of normal; total fasting cholesterol < 350 mg/dl; total triglycerides < 300 mg/dl
Who cannot join
- Ongoing oral steroid use. Patients with a history of oral steroid use are eligible as long as the steroids have been discontinued prior to study entry. Ongoing topical and/or inhaled steroid use is allowed.
- Prior taxane chemotherapy
- Prior mTOR inhibitors (RAD001, rapamycin, CCI-779)
- Currently active second malignancy other than non-melanoma skin cancer.
- Ongoing peripheral neuropathy of Grade 2
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Oregon Health Science University
Portland, Oregon
About this study
Official title: A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I).
Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II).
Read the detailed description
- Patients will be designated into one of two groups based upon the results of a FDG-PET scan.
- A patient with a baseline positive scan will have serum drawn for baseline serum proteomics assessment then be treated with RAD001 daily for two weeks. On day 10-14, another FDG-PET scan and serum assessment will be performed. An optional bone marrow biopsy may also be done. On day 15, patients will enter the Phase I portion of the trial at the current enrolling dosage or if Phase I is completed patients will enter Phase II.
- A patient that does not have a positive scan will enter directly into the Phase I trial or Phase II depending on which trial is currently enrolling.
- Phase I trial patients will have weekly laboratory evaluations and clinical evaluation every three weeks.
- Phase II trial patients will have laboratory evaluations on day one and day eight and clinical evaluation every three weeks.
- The maximum duration of the trial is one year of therapy.
- Being tested
- RAD001, Docetaxel, Prednisone
- Keywords
- prostate cancer, RAD001, mTOR inhibition, docetaxel
- Medical subject headings
- Neoplasm Metastasis, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Daily for two weeks
DocetaxelDrug
Infusion once per cycle
PrednisoneDrug
Prednisone 5 mg by mouth twice daily
| Study group | Role | What they receive |
|---|---|---|
| RAD001 Followed by RAD001 + Docetaxel | Experimental | RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily. Receives: Drug: RAD001; Drug: Docetaxel; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Free of Dose Limiting Toxicity
A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria:
Hematologic Toxicity:
CTCAE grade 4 neutropenia > 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia > 7 days
Non-hematologic toxicity:
The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following:
- CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics.
- CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor)
- CTCAE grade 3 or 4 alkaline phosphatase.
Measured: 21 days
Secondary outcomes (1)
Response Based on PET Scan
Patients were scanned using Positron Emission Tomography (PET) before and after receiving single agent RAD001. Patients were classified as having partial metabolic response, stable metabolic disease, or progressive metabolic disease based on changes in PET imaging from baseline to post-treatment. A positive FDG-PET for the purposes of this study consisted of a visualized area of abnormal increased FDG uptake that matched the anatomic location of an abnormality seen on bone scan or CT. Metabolic response was assessed for percent change in SUVmax according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC) : partial metabolic response (PMR) ≤ -25%; stable metabolic disease (SMD) -25% + 25%; progressive metabolic disease (PMD) > 25%.
Measured: 10 to 14 days after study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2007 (estimated)
- Study startNov 2005
- Primary completionDec 2012
- Study completionDec 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic, Androgen Independent Prostate CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Oregon Health and Science University
- Responsible party
- Principal investigator, Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
- Investigators
- Mary Ellen Taplin, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00459186
- Sponsor's protocol ID
- 05-184
- Status last verified
- Apr 2016
- First submitted
- 23 Jan 2006
- Last updated
- 16 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Courtney KD, Manola JB, Elfiky AA, Ross R, Oh WK, Yap JT, Van den Abbeele AD, Ryan CW, Beer TM, Loda M, Priolo C, Kantoff P, Taplin ME. A phase I study of everolimus and docetaxel in patients with castration-resistant prostate cancer. Clin Genitourin Cancer. 2015 Apr;13(2):113-23. doi: 10.1016/j.clgc.2014.08.007. Epub 2014 Oct 22.
PubMed 25450031
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
- ClinicalTrials.gov ID
- NCT00459186
- Acronym / sponsor ID
- 05-184
- Keywords
- prostate cancer, RAD001, mTOR inhibition, docetaxel
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Novartis, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Oregon Health and Science University
- Study start
- Nov 2005
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 11 Apr 2007 (estimated)
- Results
- Posted 3 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I).
Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II).
Detailed description
- Patients will be designated into one of two groups based upon the results of a FDG-PET scan.
- A patient with a baseline positive scan will have serum drawn for baseline serum proteomics assessment then be treated with RAD001 daily for two weeks. On day 10-14, another FDG-PET scan and serum assessment will be performed. An optional bone marrow biopsy may also be done. On day 15, patients will enter the Phase I portion of the trial at the current enrolling dosage or if Phase I is completed patients will enter Phase II.
- A patient that does not have a positive scan will enter directly into the Phase I trial or Phase II depending on which trial is currently enrolling.
- Phase I trial patients will have weekly laboratory evaluations and clinical evaluation every three weeks.
- Phase II trial patients will have laboratory evaluations on day one and day eight and clinical evaluation every three weeks.
- The maximum duration of the trial is one year of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 Followed by RAD001 + Docetaxel | Experimental | Drug: RAD001, Drug: Docetaxel, Drug: PrednisoneRAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adenocarcinoma of the prostate with radiographic evidence of metastatic disease.
- Willingness to undergo a baseline tumor biopsy.
- Castrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT) with evidence of progression on ADT. GnRH therapy will be continued for those on it at baseline
- Patient must have suspected tumor in an area that is safe to biopsy.
- Other prior hormonal interventions or experimental approaches are allowed. These therapies must have been discontinued for a minimum of 28 days with cancer progression.
Key exclusion criteria (5 listed)
- Ongoing oral steroid use. Patients with a history of oral steroid use are eligible as long as the steroids have been discontinued prior to study entry. Ongoing topical and/or inhaled steroid use is allowed.
- Prior taxane chemotherapy
- Prior mTOR inhibitors (RAD001, rapamycin, CCI-779)
- Currently active second malignancy other than non-melanoma skin cancer.
- Ongoing peripheral neuropathy of Grade 2
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 |
|---|---|---|
| RAD001Daily for two weeks | Drug | RAD001 Followed by RAD001 + Docetaxel |
| DocetaxelInfusion once per cycle | Drug | RAD001 Followed by RAD001 + Docetaxel |
| PrednisonePrednisone 5 mg by mouth twice daily | Drug | RAD001 Followed by RAD001 + Docetaxel |
Primary outcome
Number of Patients Free of Dose Limiting Toxicity
Time frame: 21 days
A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria: Hematologic Toxicity: CTCAE grade 4 neutropenia > 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia > 7 days Non-hematologic toxicity: The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following: 1. CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics. 2. CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor) 3. CTCAE grade 3 or 4 alkaline phosphatase.
1 secondary outcome
Response Based on PET Scan
Time frame: 10 to 14 days after study entry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25450031Courtney KD, Manola JB, Elfiky AA, Ross R, Oh WK, Yap JT, Van den Abbeele AD, Ryan CW, Beer TM, Loda M, Priolo C, Kantoff P, Taplin ME. A phase I study of everolimus and docetaxel in patients with castration-resistant prostate cancer. Clin Genitourin Cancer. 2015 Apr;13(2):113-23. doi: 10.1016/j.clgc.2014.08.007. Epub 2014 Oct 22.
Related trials for Metastatic, Androgen Independent Prostate Cancer
Not yet recruitingPhase 1/2
REGN21353 Alone or in Combination With Nezastomig for Metastatic Castration-Resistant Prostate Cancer in Adult Participants
Metastatic Castration-Resistant Prostate Cancer, mCRPC
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.
Mary Ellen Taplin, MD principal investigator
Dana-Farber Cancer Institute
5 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 RAD001, Docetaxel and Prednisone in people with Metastatic, Androgen Independent Prostate Cancer and Prostate Cancer, run by Dana-Farber Cancer Institute at 5 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 10 inclusion and 5 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 16 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 5 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 3 Mar 2014). 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?
Number of Patients Free of Dose Limiting Toxicity (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00459186, which also lists 1 linked publication.
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 16 May 2016.