Prostate Cancer Clinical Trial
Official title:
CABAzitaxel With or Without Prednisone in Patients With Metastatic CAstration REsistant Prostate Cancer (mCRPC) Progressed During or After a Previous Docetaxel-based Chemotherapy:a Multi-center,Prospective,Two-arm, Open Label, Non Inferiority Phase II Study
Verified date | October 2017 |
Source | Consorzio Oncotech |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Patients with metastatic castration resistant prostate cancer (mCRPC) progressed during or
after a previous docetaxel-based chemotherapy, for whom cabazitaxel has been scheduled as per
clinical practice and label indication.
In the "TROPIC" Trial, cabazitaxel, administered concomitantly with prednisone 10 mg daily,
showed a significant advantage vs. mitoxantrone in both Overall Survival (OS) and Progression
Free Survival (PFS) / radiographic PFS in patients failing docetaxel-based chemotherapy.
Similar to docetaxel, cabazitaxel has been approved in combination with daily prednisone, but
the benefits of adding daily corticosteroids to taxane chemotherapy remain to be proven. In
fact, corticosteroids have a variety of biological effects, and a number of studies in large
cohorts of patients show that they may have both favourable effects, mediated by adrenal
androgen and cytokine suppression, and detrimental effects related to their adverse events
associated with their long-term use as well to the potential promiscuous activation of the
AR. In fact, prednisone and dexamethasone can activate some AR variants that make tumors
sensitive to glucocorticoids even at low concentrations. It has been showed that point
mutations of the AR, which appear to cluster in the ligand-binding domain, are rare in
therapy naive patients but occur in 15- 45% of patients with castration-resistant disease and
can increase AR affinity for a wide range of steroids. On the other hand, insofar as safety
is concerned, omitting daily corticosteroids does not seem to increase toxicity (e.g.
hypersensitivity reactions). In fact, in the CHARTEED trial, docetaxel was safely
administered without daily corticosteroids. Safety data about the use of cabazitaxel without
daily prednisone/prednisone alone are missing.
The CABACARE study is designed to assess the effects in terms of efficacy, safety as well as
quality of life of omitting daily corticosteroids in patients treated with cabazitaxel.
Furthermore, the CABACARE study evaluates the mutational status of the RB gene as well as
presence of AR-V7 variant. The AR-V7 status assessed in circulating tumor cells has a strong
predictive value for abiraterone/enzalutamide effectiveness, but its role in patients
receiving cabazitaxel requires to be defined.
Status | Enrolling by invitation |
Enrollment | 220 |
Est. completion date | May 4, 2021 |
Est. primary completion date | May 4, 2021 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Signed informed consent. 2. Histological diagnosis of prostate adenocarcinoma; 3. Metastatic castration-resistant disease with documented radiographic progression (osseous or measurable lesions) during or after a docetaxel-based chemotherapy; 4. Testosterone level in the castration range (levels <50 ng/dl) because of a previous, and ongoing, androgen deprivation with LH-RH agonists or antagonists or bilateral orchiectomy; 5. Prior surgery and/or radiation therapy (to less or equal than 30% of the bone marrow) are allowed. However, at least 4 weeks must have been elapsed since surgery or completion of radiation therapy and the patient must has recovered from side effects; 6. Life expectancy = 3 months; 7. Age > 18 years; 8. ECOG performance status 0-2; 9. ANC = 1.5 x 109/L; 10. PLT = 100 x 109/L; 11. Hb = 10 g/dl; 12. Serum total bilirubin = UNL; 13. AST/SGOT and/or ALT/SGPT =1,5 x ULN; 14. Serum Creatinine =1,5 times UNL (in case of limit values of serum creatinine, creatinine clearance calculated by CKD-EPI formula should be =60 ml/min); 15. PT or INR and PTT <1,5 times UNL (Note: patients who receive anti-coagulation treatment will be allowed to participate provided that any abnormality in these parameters exists); 16. Patients must be accessible for treatment and follow up; Exclusion Criteria: 1. Participation in clinical trials with other investigational drug within 28 days of study entry; 2. Symptomatic or uncontrolled brain metastases. Patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis; previously treated brain metastases will be allowed as long as the patient is neurologically stable and does not require steroids and anticonvulsants; 3. Less than 4 weeks elapsed from prior anticancer-therapy or surgery to the time of randomization. Prior treatment with abiraterone or enzalutamide is allowed and is used as a stratification factor at randomization. Patient may be on biphosphonates prior to study entry; 4. Less than 4 weeks from palliative Radiotherapy to time of randomization; 5. Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack, pulmonary embolism or other uncontrolled thromboembolic event; 6. Any severe acute or chronic medical condition which could impair the ability of the patient to participate to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures; 7. Unstable diabetes mellitus, resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, acute diverticulitis or other contraindications to use of corticosteroid treatment; 8. Peripheral neuropathy Grade > 2 (National Cancer Institute Common Terminology Criteria (NCI CTCAE v.4.03); 9. Previous beta or gamma Isotope treatment (e.g. strontium or samarium), alpha emitters are allowed; 10. History of severe hypersensitivity reaction (> grade 2) to polysorbate 80 containing drugs; 11. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a 2-week washout period is necessary for patients who are already on these treatments); 12. Previous malignancy except for basal cell or squamous cell skin cancer adequately treated, or any other cancer from which the patient has been disease-free for = 5 years; 13. Patients with reproductive potential who do not agree to use accepted and effective method of contraception, based on the investigator's judgment, during the study treatment period. |
Country | Name | City | State |
---|---|---|---|
Italy | University Federico II of Naples | Naples |
Lead Sponsor | Collaborator |
---|---|
Consorzio Oncotech |
Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | change from Baseline radiographic progression | Radiographic progression evaluated by RECIST 1.1 criteria with bone scan, chest abdominal and pelvi TC MRI | From date of randomization until the date of first documented progression or but also during follow-up in case study treatment was discontinued without radiographic progression up to 48 months" | |
Secondary | Health-Related Quality of Life and pain | Pain response will be calculated among patients with baseline median present pain intensity score (PPI) =2 on the McGill-Melzack scale and/or baseline mean analgesic score (AS) =10 points and with stable analgesia at baseline. | from the date of randomization and the date of either first documented pain progression or death due to any cause, whichever is earlier up to 48 months" | |
Secondary | Adverse events | Incidence of Treatment-Emergent Adverse Events | From date of randomization until the date of first documented progression or but also during follow-up in case study treatment was discontinued up to 48 months" " | |
Secondary | Health-Related Quality of Life | Functional Assessment of Cancer Therapy-Prostate" (FACT-P) questionnaire, version 4. The results is summed to give a score in the range of 0-156, where higher values represent better HRQL. Questionnaires will be self-administered and takes approximately 10 minutes to complete. | From date of screening until the date of first documented progression up to 48 months" | |
Secondary | AR-V7 and RB status in circulating tumor cells | genetic blood evaluation | only at baseline |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05540392 -
An Acupuncture Study for Prostate Cancer Survivors With Urinary Issues
|
Phase 1/Phase 2 | |
Recruiting |
NCT05613023 -
A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT
|
Phase 3 | |
Recruiting |
NCT05156424 -
A Comparison of Aerobic and Resistance Exercise to Counteract Treatment Side Effects in Men With Prostate Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT03177759 -
Living With Prostate Cancer (LPC)
|
||
Completed |
NCT01331083 -
A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer
|
Phase 2 | |
Recruiting |
NCT05540782 -
A Study of Cognitive Health in Survivors of Prostate Cancer
|
||
Active, not recruiting |
NCT04742361 -
Efficacy of [18F]PSMA-1007 PET/CT in Patients With Biochemial Recurrent Prostate Cancer
|
Phase 3 | |
Completed |
NCT04400656 -
PROState Pathway Embedded Comparative Trial
|
||
Completed |
NCT02282644 -
Individual Phenotype Analysis in Patients With Castration-Resistant Prostate Cancer With CellSearch® and Flow Cytometry
|
N/A | |
Recruiting |
NCT06037954 -
A Study of Mental Health Care in People With Cancer
|
N/A | |
Recruiting |
NCT06305832 -
Salvage Radiotherapy Combined With Androgen Deprivation Therapy (ADT) With or Without Rezvilutamide in the Treatment of Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer
|
Phase 2 | |
Recruiting |
NCT05761093 -
Patient and Physician Benefit/ Risk Preferences for Treatment of mPC in Hong Kong: a Discrete Choice Experiment
|
||
Completed |
NCT04838626 -
Study of Diagnostic Performance of [18F]CTT1057 for PSMA-positive Tumors Detection
|
Phase 2/Phase 3 | |
Recruiting |
NCT03101176 -
Multiparametric Ultrasound Imaging in Prostate Cancer
|
N/A | |
Completed |
NCT03290417 -
Correlative Analysis of the Genomics of Vitamin D and Omega-3 Fatty Acid Intake in Prostate Cancer
|
N/A | |
Completed |
NCT00341939 -
Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
|
||
Completed |
NCT01497925 -
Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer
|
Phase 1 | |
Recruiting |
NCT03679819 -
Single-center Trial for the Validation of High-resolution Transrectal Ultrasound (Exact Imaging Scanner ExactVu) for the Detection of Prostate Cancer
|
||
Completed |
NCT03554317 -
COMbination of Bipolar Androgen Therapy and Nivolumab
|
Phase 2 | |
Completed |
NCT03271502 -
Effect of Anesthesia on Optic Nerve Sheath Diameter in Patients Undergoing Robot-assisted Laparoscopic Prostatectomy
|
N/A |