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Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide (CABPOSTAAT)

Primary Purpose

Metastatic Prostate Cancer

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Cabazitaxel plus prednisone
Docetaxel plus prednisone
Sponsored by
Centre hospitalier de l'Université de Montréal (CHUM)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma.
  • Metastatic disease.
  • Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate or enzalutamide by at least one of the following:
  • Progression in measurable disease (RECIST 1.1 criteria). Patient with measurable disease must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) [CT scan thickness no greater than 5 mm] or magnetic resonance imaging (MRI). Lymph nodes should be ≥ 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be ≥ 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion and bone lesions will be considered non-measurable disease, and/or
  • Appearance of 2 or more new bone lesions. They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results (PCWG2), and/or
  • Rising PSA defined (PCWG2) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. The first rising PSA (measure 2) should be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA measure is required to be taken and be greater than the 2nd measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior to randomization.
  • A PSA value of at least 2 ng/mL is required at study entry.
  • Effective castration (serum testosterone levels ≤0.5 ng/mL).
  • Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment.
  • Signed written informed consent.

Exclusion Criteria:

Related to methodology:

  • Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. Prior treatment with sipuleucel T immunotherapy is allowed at the condition patient did not received prior chemotherapy. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion.
  • Less than 28 days elapsed from prior treatment with radiotherapy or surgery to the time of randomization.
  • Prior isotope therapy, whole bony pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
  • Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.0) at the time of randomization.
  • Less than 18 years (or country's legal age of majority if the legal age is >18 years).
  • Eastern Cooperative Oncology Group (ECOG) performance status >1.
  • History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
  • Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which treatment has been completed ≥5 years ago and from which the patient has been disease-free for ≥5 years.
  • Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
  • Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
  • Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
  • 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.
  • Patients with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and up to 6 months after the last administered dose. The definition of "effective method of contraception" will be based on the investigator's judgment.

Related to study treatment

  • Known allergies, hypersensitivity or intolerance to prednisone. History of hypersensitivity to docetaxel or polysorbate 80.
  • Known history of mineralocorticoid excess or deficiency.
  • Unable to swallow a whole tablet or capsule
  • Inadequate organ and bone marrow function as evidenced by:

    1. Hemoglobin <10.0 g/dL
    2. Absolute neutrophil count <1.5 x 109/L
    3. Platelet count <100 x 109/L
    4. AST/SGOT and/or ALT/SGPT >1.5 x ULN;
    5. Total bilirubin >1.0 x ULN
    6. Potassium <3.5 mmol/L
    7. Serum albumin <3.0 g/dL
    8. Child-Pugh Class B and C
    9. Serum Creatinine ≤ 1.5 x ULN,
  • Contraindications to the use of corticosteroid treatment.
  • Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0).
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 12 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac left ventricular ejection fraction (LVEF) measurement of <50% at baseline.

Sites / Locations

  • Centre Hospitalier de l'Université de MontréalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cabazitaxel plus prednisone

Docetaxel plus prednisone

Arm Description

Cabazitaxel: Single-dose vial, containing a total of 60 mg of cabazitaxel expressed as anhydrous and solvent-free basis, per 1.5 mL of solution. Cabazitaxel will be administered by IV route Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose). Prednisone will be administered by oral route

Docetaxel is formulated in polysorbate 80 and commercially available as 80 mg/2.0 mL single-dose vials with accompanying diluent (13% ethanol in water for injection) for IV use. Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose). Prednisone will be administered by oral route

Outcomes

Primary Outcome Measures

PSA response rate at 6 and 12 months
Change from baseline PSA level of at least 50%, PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA change must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.

Secondary Outcome Measures

Radiological progression-free survival (rPFS)
Time interval between the date of randomization and the date of the first documentation of any of the following event. Radiological tumor progression by RECIST 1.1 and PCWG2,
Overall Survival
Time interval from the date of randomization to the date of death due to any cause
Time to PSA progression (TTPP)
Time interval between the date of randomization and the date of first documented PSA progression.
Tumor response
Measurable by RECIST 1.1
Duration of tumor response
Time between the first evaluation at which the tumor response criteria are met and the first documentation of tumor progression.
Pain response: BPI-SF pain intensity item scores
Decrease by <30% from baseline in the average of BPI-SF pain intensity item scores (items 3, 4, 5, and 6) observed at 2 consecutive evaluations ≥3 weeks apart without increase in analgesic usage score.
Time to Pain progression
Time interval between the date of randomization and the date of the first documented pain progression

Full Information

First Posted
December 3, 2018
Last Updated
December 20, 2022
Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT03764540
Brief Title
Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide
Acronym
CABPOSTAAT
Official Title
Randomized Phase II Study of Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide Progression
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2019 (Actual)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators
Genzyme, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men. While the majority of PCa is slow growing and responds well to first line treatment, a proportion of cases (10%) progress to metastatic form resulting in more than 4 000 deaths annually in Canada and 250 000 worldwide. Currently, first line treatment for PCa includes surgery, radiation and androgen deprivation therapy (ADT). A rapid evolution in the understanding of disease biology, combined with approvals of new therapies including immunotherapy, novel chemotherapy, hormonal agents and a bone calcium matrix-targeted radionuclide, along with further drugs in development, have made treatment decisions for metastatic castration-resistant prostate cancer (mCRPC) increasingly complex and challenging. This is a Phase II Study of Cabazitaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). The current study is designed to determine if cabazitaxel will improve progression free survival (PFS) or overall survival (OS). This study will enroll patients with mCRPC, who have been previously treated and progressed under docetaxel or abiraterone regimen. Patients must meet the study eligibility criteria and must be competent to give informed consent.
Detailed Description
This is a prospective, multicenter, national, randomized, open label study, comparing the efficacy of cabazitaxel at 25 mg/m² plus prednisone (Arm A) over docetaxel at 75mg/m2 plus prednisone (Arm B) after enzalutamide at 160 mg once daily or abiraterone acetate at 1000 mg once daily plus prednisone in chemotherapy-naïve patients with mCRPC who have progressed on abiraterone acetate or enzalutamide. Each patient will be treated until disease progression, unacceptable toxicity, or patient's refusal of further study treatment. All eligible patients will be randomly assigned to either arm A or B in a 1:1 proportion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
214 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cabazitaxel plus prednisone
Arm Type
Experimental
Arm Description
Cabazitaxel: Single-dose vial, containing a total of 60 mg of cabazitaxel expressed as anhydrous and solvent-free basis, per 1.5 mL of solution. Cabazitaxel will be administered by IV route Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose). Prednisone will be administered by oral route
Arm Title
Docetaxel plus prednisone
Arm Type
Active Comparator
Arm Description
Docetaxel is formulated in polysorbate 80 and commercially available as 80 mg/2.0 mL single-dose vials with accompanying diluent (13% ethanol in water for injection) for IV use. Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose). Prednisone will be administered by oral route
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel plus prednisone
Other Intervention Name(s)
Experimental
Intervention Description
Cabazitaxel 25 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily. A cycle is defined as a 3-weeks period for a maximum of 10 cycles.
Intervention Type
Drug
Intervention Name(s)
Docetaxel plus prednisone
Other Intervention Name(s)
Active Comparator
Intervention Description
Docetaxel 75 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily. A cycle is defined as a 3-weeks period for a maximum of 10 cycles.
Primary Outcome Measure Information:
Title
PSA response rate at 6 and 12 months
Description
Change from baseline PSA level of at least 50%, PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA change must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.
Time Frame
through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
Radiological progression-free survival (rPFS)
Description
Time interval between the date of randomization and the date of the first documentation of any of the following event. Radiological tumor progression by RECIST 1.1 and PCWG2,
Time Frame
through study completion, an average of 1 year
Title
Overall Survival
Description
Time interval from the date of randomization to the date of death due to any cause
Time Frame
through study completion, an average of 1 year
Title
Time to PSA progression (TTPP)
Description
Time interval between the date of randomization and the date of first documented PSA progression.
Time Frame
through study completion, an average of 1 year
Title
Tumor response
Description
Measurable by RECIST 1.1
Time Frame
through study completion, an average of 1 year
Title
Duration of tumor response
Description
Time between the first evaluation at which the tumor response criteria are met and the first documentation of tumor progression.
Time Frame
hrough study completion, an average of 1 year
Title
Pain response: BPI-SF pain intensity item scores
Description
Decrease by <30% from baseline in the average of BPI-SF pain intensity item scores (items 3, 4, 5, and 6) observed at 2 consecutive evaluations ≥3 weeks apart without increase in analgesic usage score.
Time Frame
through study completion, an average of 1 year
Title
Time to Pain progression
Description
Time interval between the date of randomization and the date of the first documented pain progression
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma. Metastatic disease. Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate or enzalutamide by at least one of the following: Progression in measurable disease (RECIST 1.1 criteria). Patient with measurable disease must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) [CT scan thickness no greater than 5 mm] or magnetic resonance imaging (MRI). Lymph nodes should be ≥ 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be ≥ 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion and bone lesions will be considered non-measurable disease, and/or Appearance of 2 or more new bone lesions. They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results (PCWG2), and/or Rising PSA defined (PCWG2) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. The first rising PSA (measure 2) should be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA measure is required to be taken and be greater than the 2nd measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior to randomization. A PSA value of at least 2 ng/mL is required at study entry. Effective castration (serum testosterone levels ≤0.5 ng/mL). Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment. Signed written informed consent. Exclusion Criteria: Related to methodology: Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. Prior treatment with sipuleucel T immunotherapy is allowed at the condition patient did not received prior chemotherapy. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion. Less than 28 days elapsed from prior treatment with radiotherapy or surgery to the time of randomization. Prior isotope therapy, whole bony pelvic radiotherapy, or radiotherapy to >30% of bone marrow. Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.0) at the time of randomization. Less than 18 years (or country's legal age of majority if the legal age is >18 years). Eastern Cooperative Oncology Group (ECOG) performance status >1. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which treatment has been completed ≥5 years ago and from which the patient has been disease-free for ≥5 years. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization. Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event. Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment. 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. Patients with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and up to 6 months after the last administered dose. The definition of "effective method of contraception" will be based on the investigator's judgment. Related to study treatment Known allergies, hypersensitivity or intolerance to prednisone. History of hypersensitivity to docetaxel or polysorbate 80. Known history of mineralocorticoid excess or deficiency. Unable to swallow a whole tablet or capsule Inadequate organ and bone marrow function as evidenced by: Hemoglobin <10.0 g/dL Absolute neutrophil count <1.5 x 109/L Platelet count <100 x 109/L AST/SGOT and/or ALT/SGPT >1.5 x ULN; Total bilirubin >1.0 x ULN Potassium <3.5 mmol/L Serum albumin <3.0 g/dL Child-Pugh Class B and C Serum Creatinine ≤ 1.5 x ULN, Contraindications to the use of corticosteroid treatment. Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0). Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 12 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac left ventricular ejection fraction (LVEF) measurement of <50% at baseline.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amal Nadiri, PhD
Phone
514 890-8000
Ext
26074
Email
amal.nadiri.chum@ssss.gouv.qc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
fred Saad, MD
Organizational Affiliation
CHUM
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 3E4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
fred Saad, MD
Phone
5148908000
Email
fredsaad@videotron.ca
First Name & Middle Initial & Last Name & Degree
Amal Nadiri, Ph,D
Phone
514890800026074
Email
amal.nadiri.chum@ssss.gouv.qc.ca

12. IPD Sharing Statement

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Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide

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