Study of Weekly Cabazitaxel for Advanced Prostate Cancer
This is a multicenter open label non randomized phase II clinical trial of Weekly Cabazitaxel for Advanced Prostate Cancer in Hormone-Refractory Patients Previously Treated with Docetaxel.
The purpose of this study is to evaluate the activity of the weekly administration of cabazitaxel as time to progression by PSA at week 12.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Weekly Cabazitaxel for Advanced Prostate Cancer in "Unfit" Hormone-Refractory Patients Previously Treated With Docetaxel|
- Time to progression by PSA at week 12, according to the PCCTWG II criteria. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Time to progression by PSA at week 12. PSA progression defined as an increase of ≥25% over nadir PSA concentration provided that the increase in the absolute PSA value was ≥5 μg/L for men with no PSA response, or ≥50% over nadir for PSA responders and PSA responders defined as a reduction in serum PSA concentration of ≥50% in patients with a baseline value of ≥20 μg/L.
- time to PSA progression [ Time Frame: Patients will be followed until PSA progression, an expected average of 6 months ] [ Designated as safety issue: No ]Time to PSA progression, according to the PCCTWG II criteria, defined as the time between enrolment and the first date of PSA progression.
- biochemical response rate [ Time Frame: Patients will be followed until end of treatment, an expected average of 6 months ] [ Designated as safety issue: No ]Biochemical response by PSA determination defined as the percentage of patients with 30%,50% and 80% reduction respect to baseline in patients with a baseline value >=20 mcg/L confirmed by a repeat PSA measurement after at least 3 weeks.
- Objective response rate [ Time Frame: Patients will be followed until end of treatment, an expected average of 6 months ] [ Designated as safety issue: No ]Proportion of patients with an objective tumoral response according to modified RECIST criteria
- Overall survival [ Time Frame: Patients will be followed until death, an expected average of 18 months ] [ Designated as safety issue: No ]Overall survival is calculated since the date of patient study enrolment till death.
- Evaluate the safety and tolerability profile of cabazitaxel. [ Time Frame: 6 months (during treatment) ] [ Designated as safety issue: Yes ]
All adverse events will be graded according to National Cancer Institute Common Terminology Criteria for adverse events (version 4.03).
Adverse events, biochemistry, hematology, vital signs and electrocardiograms will be monitored throughout the study.
- Pain response [ Time Frame: Until end of treatment, an expected average of 6 months ] [ Designated as safety issue: No ]Determine the pain response in patients with stable pain at baseline by means of the McGill-Melzack MPQ-sf questionnaire, defined as ≥ 2 points with respect to baseline on the PPI scale without increase in the analgesic scale, or with a decrease of ≥ 50% in the use of analgesics without an increase in pain that is maintained for more than 3 weeks.
- Correlation between presence-absence of baseline pain with overall survival, time to progression and PSA response rate. [ Time Frame: Until death, an expected average of 18 months ] [ Designated as safety issue: No ]
- Correlation of the Charlson co-morbidity index and ADL/IADL dependency indexes with survival and toxicity [ Time Frame: Until death, an expected average of 18 months ] [ Designated as safety issue: No ]
- Assessment and quantification of Circulating Tumour Cells and level correlation between the beginning of treatment and their variation through treatment with time to progression and overall survival [ Time Frame: Until death, an expected average of 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||September 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Drug: Cabazitaxel 10 mg/m2
Drug: Cabazitaxel 10 mg/m2
Cabazitaxel 10 mg/m2 in a 1-hour infusion on days 1, 8, 15 and 22 of 5-week cycles.
Other Name: Jevtana
The efficacy of three-weekly cabazitaxel is accompanied by an appreciable rate of serious side effects and toxic deaths. The toxicity rates observed, including grade III-IV neutropenia, febrile neutropenia and diarrhea, could be an obstacle to the use and management of a drug that, on the other hand, has demonstrated great activity. In the treatment of patients with prostate cancer, who have a larger number of morbidities than patients with breast cancer, we assume the risk that in the transition from clinical trial to clinical practice the drug will not be used much because of the risk of side effects, cost, the discomfort derived from the routine use of G-CSF and the lack of patient compliance with this type of regimens.
Rates of neuropathy, nail and conjunctive toxicity with this new taxane are not relevant, which suggests that weekly administration will not produce relevant toxicity problems. Weekly administration of other taxanes improved hematologic tolerance along with a better therapeutic range in some cases, increasing the dose intensity and activity without increasing the associated toxicity.
Phase I study has been reported studying weekly administration of cabazitaxel, recommended dose is 10 mg/m2, administered on days 1, 8, 15 and 22 every 5 weeks in a 1-hour infusion, being diarrhea the dose-limiting toxicity observed in this study.
Given the pharmacokinetic characteristics of this taxane and its activity and toxicity profile, cabazitaxel might be a good candidate for studying in a weekly administration regimen in patients with prostate cancer with a greater risk of toxicity associated with treatment every 3 weeks, such as patients who have received previous pelvic radiation therapy that affects more than 25% of the bone marrow reserve, patients over 75 years with a worse performance status (ECOG 2) or who have already experienced important hematologic toxicity in the previous treatment with docetaxel.
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|Hospital Universitario Fundación Alcorcón||Recruiting|
|Alcorcón (MADRID), Spain, 28922|
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|Principal Investigator: Jesus García-Donas, MD|
|Hospital Clinic I Provincial de Barcelona||Recruiting|
|Barcelona, Spain, 08036|
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|Institut Català D'Oncologia L'Hospitalet (Ico)||Recruiting|
|Hospitalet de Llobregat (Barcelona), Spain, 08908|
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|Principal Investigator: Jose R Germá i Lluch, MD|
|Hospital Universitario 12 de Octubre||Recruiting|
|Madrid, Spain, 28041|
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|Principal Investigator: Daniel E Castellano, MD|
|Hospital General Universitario Gregorio Marañón||Recruiting|
|Madrid, Spain, 28007|
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|Hospital de Sant Joan de Déu||Recruiting|
|Manresa (Barcelona), Spain, 08243|
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|Ourense, Spain, 32005|
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|Sevilla, Spain, 41014|
|Contact: Eva M Fernández Parra, MD +34 955016020 firstname.lastname@example.org|
|Principal Investigator: Eva M Fernández Parra, MD|
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|Principal Investigator:||Miguel A Climent, MD||FUNDACIÓN INSTITUTO VALENCIANO DE ONCOLOGÍA, Servicio de Oncología Médica, Profesor Beltrán Báguena, 11, 8 y 19, Valencia, 46009|