Orteronel Maintenance Therapy in Patients With mCRPC Previously Treated With Novel Hormonal Agents
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02053311|
Recruitment Status : Withdrawn (Due to former trials, drug has not demonstrated a clinical profile sufficient to move forward in mCRPC)
First Posted : February 3, 2014
Last Update Posted : July 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Orteronel Drug: Placebo||Phase 3|
One in six men will be diagnosed with cancer of the prostate during his lifetime. Accordingly, prostate cancer is the most common cancer amongst men in the western world. In Switzerland approx. 5'400 men are diagnosed with the disease and 1'300 die of prostate cancer every year. Prostate cancer represents 30% of all cancer diagnoses in men. Despite earlier detection and new treatments the life time risk to die of prostate cancer has remained stable at 3% since 1980.
In metastatic castration-resistant prostate cancer (with progression on antihormonal therapy) the primary standard therapy for a long time consisted of chemotherapy with docetaxel. It was recently shown that treatment with the novel androgen synthesis blocker, abiraterone (Zytiga) before chemotherapy can prolong survival. Abiraterone belongs to a group of agents that very effectively inhibits the androgen synthesis via blockade of the key enzyme cytochrome P-450c17 (CYP17).Similar results have been reported for the new androgen antagonist enzalutamide (Xtandi). Today, therefore, many patients with metastatic castration-resistant prostate cancer (mCRPC) first receive therapy with abiraterone or enzalutamide. After this, chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana) is usually administered if there is any further progression of the disease. After the end of chemotherapy, the patient is regularly checked and, in the event of disease progression, further treatments may be given. These could consist of renewed hormonal therapy or chemotherapy with cabazitaxel. Besides abiraterone, the medicine orteronel also acts by blocking testosterone production via the key enzyme CYP17. By selectively inhibiting the extragonadal synthesis of androgens in either the adrenal cortex or in prostate tumor cells, orteronel, a selective non-steroidal CYP17 inhibitor, may represent a new therapeutic option for patients with CRPC. Initial results have shown that orteronel effectively inhibits testosterone synthesis.
Hypothesis and aim of the study
Since various new options are available for treatment of castration-resistant prostate cancer at present, this raises the question as to the order in which these treatments should best be given. Initial results show that cross-resistance could develop between the new kinds of hormone therapy abiraterone and enzalutamide. There is evidence to suggest that any resistance to hormone treatments could be reversible as a result of prior treatment with chemotherapy. This study is designed to investigate this approach. It is also intended to investigate whether early use of the well-tolerated testosterone synthesis blocker orteronel in patients with mCRPC leads to an increase in the time to the progression of disease. Trials examining other advanced malignant diseases such as lung cancer have shown that initiating an effective treatment earlier in the disease course at the end of a first-line chemotherapy (so called switch maintenance therapy) is beneficial in terms of progression free survival (PFS) but also overall survival (OS). This may also hold true for early administration of antihormonal agents in patients with mCRPC.
Patients who have already received a novel hormonal therapy followed by chemotherapy with a taxane and have experienced a stabilization of disease on this regimen are included in the study. It is also intended to test whether this treatment has a positive influence on the quality of life of patients.
The aim of this trial is to test the hypothesis that using orteronel treatment immediately after cessation of chemotherapy with a taxane can prolong event-free survival (EFS), consequently maintains a good quality of life (QL) and could eventually also improve overall survival for the group of patients pretreated with novel hormonal agents.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Orteronel Maintenance Therapy in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) Previously Treated With Novel Hormonal Agents and Non-progressive Disease After Treatment With a Taxane: A Multicentre Randomized Double-blind Placebo-controlled Phase III Trial|
|Actual Study Start Date :||August 19, 2014|
|Actual Primary Completion Date :||August 19, 2014|
|Estimated Study Completion Date :||August 19, 2034|
Active Comparator: Arm A: Orteronel
300mg orteronel twice daily and best supportive care until disease progression
Other Name: TAK-700
Active Comparator: Arm B: Placebo
Placebo twice daily and best supportive care until disease progression
- Event-free survival [ Time Frame: 5 months ]
The primary endpoint of the trial is EFS. An event is defined as ONE of the following:
- death from any cause
- the presence of radiographic progression AND symptomatic/clinical progression
- the presence of radiographic progression AND PSA progression
- the presence of symptomatic/clinical progression AND PSA progression
- Adverse events (AEs) [ Time Frame: Throughout treatment phase (estimated up to 1 year) until 30 days after last drug administration or prior to start of subsequent anticancer treatment (whichever occurs first) ]All AEs will be assessed according to NCI CTCAE v4.0.
- Prostate-specific antigen (PSA) response (30%, 50%, 90% and best) [ Time Frame: PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year) ]
- Time to PSA progression [ Time Frame: PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year) ]
- Radiographic progression-free survival (rPFS) [ Time Frame: Every 12 weeks until disease progression (estimated up to 1 year) ]
- Overall survival (OS) [ Time Frame: time from trial randomization to the date of death from any cause (estimated up to 4 years) ]
- Quality of Life (QL) [ Time Frame: First 6 months of trial treatment ]
- Pain Response [ Time Frame: First 6 months of trial treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02053311
|Baden, Switzerland, CH-5404|
|Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli|
|Bellinzona, Switzerland, 6500|
|Chur, Switzerland, CH-7000|
|Luzerne, Switzerland, CH-6000|
|Münsterlingen, Switzerland, 8596|
|Kantonsspital - St. Gallen|
|St. Gallen, Switzerland, CH-9007|
|SpitalSTS AG Simmental-Thun-Saanenland|
|Thun, Switzerland, 3600|
|Study Chair:||Richard Cathomas, MD||Kantonsspital Graubünden|
|Study Chair:||Silke Gillessen, Prof||Cantonal Hospital of St. Gallen|