Clinical trial NCT02441894: Combination of Cabazitaxel With Prednisolone With Primary Prophylaxis With PEG-G-CSF in Treatment of Patients With Prostate Cancer
Official title: Cabazitaxel in Combination With Prednisolone With Primary Prophylaxis With PEG-G-CSF for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prostate Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-05-12
Enrollment: 21
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To assess the tolerability of cabazitaxel 25 mg per body surface area (m\^2) with primary prophylactic polyethylene glycol-granulocyte-colony stimulating factor (PEG-G-CSF) in terms of the incidence rate of febrile neutropenia (FN) (defined: absolute neutrophil count \[ANC\] \<1000 per volume \[mm\^3\] and a single temperature of \>38.3 degree or a sustained temperature of ≥38 degree Celsius for more than one hour) during Cycle 1.

Secondary Objective:

To assess overall rate of FN and grade ≥3 neutropenia and diarrhea; frequencies of dose delay due to adverse events (AEs); dose reduction due to AEs; relative dose intensity; incidences of FN-related hospitalization and use of intravenous (IV) anti-infectives; tolerability according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0; prostate specific antigen (PSA) response (50% decrease); tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 if available.

Detailed description: The total duration of study is 254 days as maximum with 14 days for screening, maximum of 21 days times 10 cycles for treatment, and 30 days for follow up.

Eligibility criteria: Inclusion criteria:

* Patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with chemotherapy including docetaxel.
* Male patients.
* Patients must have either measurable or nonmeasurable disease, or documented rising PSA levels.
* Patients signed informed consent.

Exclusion criteria:

* Age \<20 at registration.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2.
* Inadequate organ and bone marrow function at registration as evidenced by:

  * Hemoglobin \<10.0 g/dL.
  * ANC \<5 x 10\^9/L.
  * Platelet count \<100 x 10\^9/L.
  * Aspartate transaminase (AST) and/or alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN).
  * Total bilirubin \>1.0 x ULN.
  * Serum creatinine \>1.5 x ULN. Serum creatinine is 1.0-1.5 x ULN and creatinine clearance is under 60 mL/min (calculated according to Chronic Kidney Disease Epidemiology Collaboration \[CKD-EP\]).
* Prior isotope therapy or radiotherapy to ≥30% of bone marrow. At the first study drug administration day, patient has not elapsed 8 weeks (12 weeks for strontium-89) from the day prior isotope therapy finished.
* Prior surgery, radiation, chemotherapy, or other anticancer therapy within 4 weeks prior to enrollment in the study.
* Symptomatic peripheral neuropathy grade ≥2 (NCI CTCAE v.4.0).
* History of severe hypersensitivity reaction (grade ≥3) to polysorbate 80 containing drugs.
* Prior and other concurrent malignancy, excepted cases are as follows; basal cell carcinoma or squamous cell carcinoma of skin, or superficial (pTis, pTa, and pT1) bladder cancer (including immunotherapy) treated adequately, any other cancer completed the chemotherapy more than 5 years ago and been more than 5 years as disease free duration.
* Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus).
* Known lesion at brain or leptomeninx.
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.
* Active varicella zoster infection, anti-hepatitis C virus (HCV) antibody-positive (excluding patients negative for HCV virus in blood test or non-active seropositive patients with no hepatic abnormalities \[AST, ALT, etc.\]), or hepatitis B surface (HBs) antigen-positive.
* Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4 or 5 (wash-out period for a one week is necessary for patients who are already on these treatments or a two-week wash-out period is necessary for patients who are already on these treatments).
* Contraindication to be used corticosteroid.
* Patients with reproductive potential who do not agree to use an accepted and effective method of contraception during the study treatment period. The definition of "effective method of contraception" will be based on the Investigator's judgment.
* Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to registration.
* Prior history of severe hypersensitivity reaction (≥grade 3) or intolerance to prednisolone, PEG-G-CSF or G-CSF.
* Known hypersensitivity to the component of PEG-G-CSF and/or G-CSF.
* Myelogenous leukemia insufficient decrease of the number of blast in bone marrow, or found myeloblast in peripheral blood.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Number of patients with FN (all grades) during study Cycle 1
timeFrame: 3 weeks (during study Cycle 1)
Secondary outcomes:
measure: Number of patients with FN (all grades)
timeFrame: Up to 7 months as treatment period
measure: Number of patients with Grade ≥3 neutropenia
timeFrame: Up to 7 months as treatment period
measure: Number of patients with Grade ≥3 diarrhea
timeFrame: Up to 7 months as treatment period
measure: Number of dose delays in the start of drug administration due to AEs
timeFrame: Up to 7 months as treatment period
measure: Number of dose reductions due to AEs
timeFrame: Up to 7 months as treatment period
measure: Percent change in relative dose intensity due to AEs
timeFrame: Up to 7 months as treatment period
measure: Number of patients with FN-related hospitalization
timeFrame: Up to 7 months as treatment period
measure: Number of patients who used IV anti-infective drugs
timeFrame: Up to 7 months as treatment period
measure: Changes of PSA levels from baseline
timeFrame: Up to 7 months as treatment period
measure: Number of patients with adverse events
timeFrame: Up to 7 months as treatment period
Other outcomes:
Locations:
city: Chuo-ku, Chiba
country: Japan
facility: Investigational Site Number 392004
city: Kita-gun
country: Japan
facility: Investigational Site Number 392008
city: Kobe-shi, Hyogo
country: Japan
facility: Investigational Site Number 392007
city: Nagakute-shi, Aichi
country: Japan
facility: Investigational Site Number 392005
city: Osaka Sayama-shi, Osaka
country: Japan
facility: Investigational Site Number 392006
city: Shinjuku-ku, Tokyo
country: Japan
facility: Investigational Site Number 392001
city: Yokohama-shi, Kanagawa
country: Japan
facility: Investigational Site Number 392002
city: Yokohama-shi
country: Japan
facility: Investigational Site Number 392009
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Kosaka T, Uemura H, Sumitomo M, Harada K, Sugimoto M, Hayashi N, Yoshimura K, Fukasawa S, Ecstein-Fraisse E, Sunaga Y, Oya M. Impact of pegfilgrastim as primary prophylaxis for metastatic castration-resistant prostate cancer patients undergoing cabazitaxel treatment: an open-label study in Japan. Jpn J Clin Oncol. 2019 Aug 1;49(8):766-771. doi: 10.1093/jjco/hyz051.