Study of Weekly Cabazitaxel for Advanced Prostate Cancer

This study is currently recruiting participants.
Verified July 2013 by Spanish Oncology Genito-Urinary Group
Sponsor:
Information provided by (Responsible Party):
Spanish Oncology Genito-Urinary Group
ClinicalTrials.gov Identifier:
NCT01518283
First received: January 17, 2012
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Hormone Refractory Prostate Cancer
Drug: Cabazitaxel 10 mg/m2
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Spanish Oncology Genito-Urinary Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 74
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)
Arms Assigned Interventions
Experimental: Cabazitaxel
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who have given written informed consent.
  2. Age ≥ 18 years.
  3. ECOG 0-2.
  4. Patients with a histologic or cytologic diagnosis of advanced prostate cancer (any Gleason grade).
  5. Previous and ongoing castration by orchiectomy or LHRH agonists. Antiandrogen must be discontinued prior to study start.
  6. Disease progression, clinically or radiologically documented, during or after treatment with docetaxel, with a minimum cumulative dose of 225 mg/m2.
  7. "Unfit" patients defined as patients who satisfy at least one of the following criteria:

    • ECOG 2
    • Dose reduction due to febrile neutropenia during the previous treatment with docetaxel
    • Radiation therapy affecting more than 25% of bone marrow reserve
  8. Documented metastatic disease and progressing after docetaxel treatment. Progression criteria is considered any of the following three or more than one at once:

    • Progressive elevation of PSA measured in three successive determinations one week difference between them at least;
    • Should be considered progression of measurable disease by RECIST criteria;
    • Bone progression as evidenced by the appearance of two or more new lesions on bone scan.
  9. Patients who have received a maximum of one prior chemotherapy for metastatic disease.
  10. Prior anticancer therapy should have been interrupted 28 days before the start of study treatment (the patient may have continued treatment with prednisone 5 mg bid.
  11. Adequate blood, liver and kidney function:

    • Hemoglobin > 9.0 g/dl
    • ANC > 1.5 x 10*9/L
    • Platelets > 100 x 10*9/L
    • AST/SGOT and ALT/SGPT < 2.5 x ULN
    • Bilirubin < 1.0 x ULN
    • Creatinine <1.5 mg/dL x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded (see Annex 7 for formula)
  12. Adequate baseline cardiac function (LVEF ≥ 50%).
  13. Life expectancy ≥ 12 weeks.
  14. Patients must agree to use an effective contraceptive method during treatment with the study drug and up to 1 month after ending the treatment.

Exclusion Criteria:

  1. Patients who received radiation therapy that exceeded 40% of the bone marrow reserve or that ended within the last 3 weeks prior to inclusion.
  2. If being treated with radiation therapy, should be completed before the three weeks prior to initiation of treatment research.
  3. Previous treatment with two or more chemotherapy regimens for metastatic disease. A new line of treatment is also when a patient receives again docetaxel after clinical, radiological or PSA progression to a prior regimen with docetaxel.
  4. Previous treatment with chemotherapy or surgery in the last 4 weeks.
  5. Peripheral neuropathy or stomatitis ≥ 2 (National Cancer Institute Common Terminology Criteria - NCI CTCAE vs. 4.03).
  6. Any other type of cancer in the last 5 years, except for basal cell skin carcinoma.
  7. Cerebral or leptomeningeal metastasis.
  8. Myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass, congestive heart failure (NYHA class III or IV), stroke or transitory ischemic episodes.
  9. Patients who present any severe or uncontrolled medical condition (including uncontrolled diabetes mellitus) or any other condition that may affect the patient's participation and study compliance.
  10. Previous treatment with cabazitaxel.
  11. Known hypersensitivity (≥ grade 3)to cabazitaxel, polysorbate 80, prednisone or prednisolone, or docetaxel or paclitaxel.
  12. Known history of active infection that requires systemic antibiotic or antifungal treatment.
  13. Patients who are receiving or expect to receive treatment with strong inhibitors or strong inducers of cytochrome CYP450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Annexes 5 and 6).
  14. Patients being treated with any investigational product.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01518283

Contacts
Contact: Daniel E Castellano, MD +34 914692313 cdanicas@hotmail.com
Contact: Juan L Sanz +34 918166804 ext 103 juanluis.sanz@apices.es

Locations
Spain
Hospital Universitario Fundación Alcorcón Recruiting
Alcorcón (MADRID), Spain, 28922
Contact: Susana Hernando, MD    +34 916219490    shernando@fhalcorcon.es   
Principal Investigator: Jesus García-Donas, MD         
Hospital Clinic I Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Begoña Mellado, MD    +34 932275402    bmellado@clinic.ub.es   
Principal Investigator: Begoña Mellado, MD         
Institut Català D'Oncologia L'Hospitalet (Ico) Recruiting
Hospitalet de Llobregat (Barcelona), Spain, 08908
Contact: Jose R Germá i Lluch, MD    +34 932607744    jrgerma@iconcologia.net   
Principal Investigator: Jose R Germá i Lluch, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Daniel E Castellano, MD    +34 914692313    cdanicas@hotmail.com   
Principal Investigator: Daniel E Castellano, MD         
Hospital General Universitario Gregorio Marañón Recruiting
Madrid, Spain, 28007
Contact: Jose A Arranz, MD    +34 915868115    jarranza.oncomed@gmail.com   
Principal Investigator: Jose A Arranz, MD         
Hospital de Sant Joan de Déu Recruiting
Manresa (Barcelona), Spain, 08243
Contact: Montserrat Domenech, MD    +34 938742112 ext 3221    mdomenech@althaia.cat   
Principal Investigator: Montserrat Domenech, MD         
Complejo Hospitalario de Ourense Recruiting
Ourense, Spain, 32005
Contact: Ovidio Fernandez Calvo, MD    +34 988385471    ovidio.fernandez.calvo@sergas.es   
Principal Investigator: Ovidio Fernandez Calvo, MD         
Complejo Hospitalario Universitario de Santiago Recruiting
Santiago de Compostela (LA CORUÑA), Spain, 15706
Contact: Urbano Anido, MD    +34 981950544    urbano.anido.herranz@sergas.es   
Principal Investigator: Urbano Anido, MD         
Hospital Nuestra Señora de Valme Recruiting
Sevilla, Spain, 41014
Contact: Eva M Fernández Parra, MD    +34 955016020    evamfparra@yahoo.es   
Principal Investigator: Eva M Fernández Parra, MD         
Hospital Virgen Del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Begoña Perez Valderrama, MD    +34 955013068    bperezv@gmail.com   
Principal Investigator: Begoña Perez Valderrama, MD         
Consorcio Hospital General Universitario de Valencia Recruiting
Valencia, Spain, 46014
Contact: Cristina Caballero, Md    +34 961972151    caballero_cri@gva.es   
Principal Investigator: Criatina Caballero, MD         
Fundación Instituto Valenciano de Oncología Recruiting
Valencia, Spain, 46009
Contact: Miguel A Climent, MD    +34 961114334    macliment@fivo.org   
Principal Investigator: Miguel A Climent, MD         
Sponsors and Collaborators
Spanish Oncology Genito-Urinary Group
Investigators
Principal Investigator: Miguel A Climent, MD FUNDACIÓN INSTITUTO VALENCIANO DE ONCOLOGÍA, Servicio de Oncología Médica, Profesor Beltrán Báguena, 11, 8 y 19, Valencia, 46009
  More Information

No publications provided

Responsible Party: Spanish Oncology Genito-Urinary Group
ClinicalTrials.gov Identifier: NCT01518283     History of Changes
Other Study ID Numbers: CABASEM-SOGUG
Study First Received: January 17, 2012
Last Updated: July 3, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Spanish Oncology Genito-Urinary Group:
Weekly cabazitaxel.
Advanced Hormone-refractory prostate Cancer.
Unfit patients.

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 17, 2014