TerminatedNCT02379390PRIMCABUpdated Jun 21, 2019Results posted

Cabazitaxel Versus the Switch to Alternative AR Targeted Therapy Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Primary Resistant Patients to Abiraterone or Enzalutamide

A Phase 2 interventional study of Cabazitaxel XRP6258 and Ezalutamide in Prostate Cancer Metastatic, sponsored by Sanofi. Terminated at 24 sites in 2 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-06-21.

Sponsored by Sanofi · Phase 2, Interventional, and Treatment

Why this study was terminated

Unsatisfactory patient accrual

Phase: Phase 2
Study type: Interventional
Enrollment: 8
Allocation: Randomized
Ages: 18 Years and older
Sex: Male

Study summary

Primary Objective:

To demonstrate the superiority in term of radiographic Progression-Free Survival (rPFS) of cabazitaxel at at 25 milligram per meter square (mg/m\^2) plus prednisone (Arm A) versus either enzalutamide at 160 milligram (mg) once daily or abiraterone acetate at 1000 mg once daily plus prednisone (Arm B) in chemotherapy-naïve participants with metastatic Castration-Resistant Prostate Cancer (mCRPC) who have disease progression while receiving androgen receptor (AR) targeted therapy (abiraterone plus prednisone or enzalutamide) within 12 months of treatment initiation (≤12 months).

Secondary Objective:

To compare efficacy for:
Prostate-specific antigen (PSA) response rate and Time to PSA progression (TTPP).
Progression Free Survival (PFS).
Overall Survival (OS).
Tumor response rate in participants with measurable disease (RECIST 1.1)
Pain response and time to pain progression.
Symptomatic skeletal events (SSE) rate and time to occurrence of any SSE.
To analyze messenger ribonucleic acids (mRNAs) including androgen-receptor splice variant 7 messenger RNA (AR-V7) as a biomarker in Circulating Tumor Cells (CTCs).
To evaluate safety in the 2 treatment arms.

Read the detailed description

The duration of the study per participant was approximately 2 years. Each participant was treated until radiographic disease progression, unacceptable toxicity, or participants refusal of further study treatment, and each participant was followed after completion of study treatment until death, study cutoff date, or withdrawal of participant consent.

Conditions studied

Prostate Cancer Metastatic

Browse trials for

Prostatic Neoplasms 6,370

In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.

This study's enrollment of 8 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Male
Accepts healthy volunteers: No

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 within 12 months of treatment initiation (≤12 months) by at least one of the following:
Progression in measurable disease Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG2).
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.
A PSA value of at least 2 nanogram/milliliter (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

Exclusion criteria:

Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion. Prior docetaxel in hormone sensitive setting is allowed if completed >1 year before randomization. Prior immunotherapy is allowed.
Less than 28 days elapsed from prior treatment with immunotherapy, radiotherapy, or surgery to the time of randomization.
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 for Adverse Events [NCI CTCAE] v4.0) at the time of randomization.
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.
Acquired immunodeficiency syndrome (AIDS)-related illnesses or known Human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.
Any severe acute or chronic medical condition including uncontrolled diabetes mellitus, severe renal impairment, history of cardiovascular disease (uncontrolled hypertension, arterial thrombotic events in the past 6 months, congestive heart failure, severe or unstable angina pectoris, recent myocardial infraction within last 6 months or uncontrolled cardiac arrhythmia), 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.
Participants 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.
Known allergies, hypersensitivity or intolerance to prednisone or excipients of abiraterone acetate or enzalutamide. History of hypersensitivity to docetaxel or polysorbate 80.
Known history of mineralocorticoid excess or deficiency (not applicable to participants who have already been treated with abiraterone acetate in first line before inclusion).
History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold (not applicable to participants who have already been treated with enzalutamide in first line before inclusion).
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 10\^9/L.
Platelet count \<100 x 10\^9/L.
Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) >1.5 x Upper limit of normal (ULN).
Total bilirubin >1.0 x ULN.
Potassium \<3.5 mmol/L.
Serum albumin \<3.0 g/dL.
Child-Pugh Class B and C.
Contraindications to the use of corticosteroid treatment.
Symptomatic peripheral neuropathy grade ≥2 NCI CTCAE v4.0.
Concomitant vaccination with yellow fever vaccine.

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 8 participants (actual)

Study arms

Experimental
Cabazitaxel
Participants received Cabazitaxel 25 mg/m\^2, intravenously for 1 hour along with prednisone 10 mg orally on Day 1 of every treatment cycle (each cycle was of 3 weeks) until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
Drug: Cabazitaxel XRP6258 · Drug: Prednisone
Active comparator
Abiraterone acetate or Enzalutamide
Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally once daily along with prednisone 5 mg, orally twice daily from Day 1 to 21 in each treatment cycle (each cycle was of 3 weeks) or enzalutamide 160 mg, orally, until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
Drug: Ezalutamide · Drug: Abiraterone acetate · Drug: Prednisone

Interventions

DrugCabazitaxel XRP6258
Also known as: Jevtana
DrugEzalutamide
Also known as: Xtandi
DrugAbiraterone acetate
Also known as: Zytiga
DrugPrednisone

What researchers measure

Primary outcomes

Radiographic Progression-Free Survival (rPFS)
rPFS was defined as the time from randomization to the first occurrence of radiological tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or progression of bone lesions using prostate cancer working group 2 (PCWG2) criteria or death due to any cause.
Time frame: Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)

Secondary outcomes

Number of Participants With Prostate Specific Antigen (PSA) Response
PSA response was defined as decline of serum PSA from baseline by \>= 50 percent (%).
Time frame: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
Progression-free Survival (PFS)
PFS: time interval between date of randomization to first documentation of tumor progression as per RECIST 1.1.
Time frame: Baseline upto progression or death due to any cause (maximum duration: 1059 days)
Overall Survival
Overall Survival was defined as the time interval from the date of randomization to the date of death due to any cause.
Time frame: Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days)
Time to PSA Progression
Time to PSA progression was defined as the time interval between the date of randomization and the date of first documented PSA progression as per PCWG2 criteria.
Time frame: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
Number of Participants Achieving Tumor Response
Tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1.
Time frame: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
Duration of Tumor Response
Duration of tumor response was defined as the time between the first evaluation at which the tumor response criteria were met and the first documentation of tumor progression.
Time frame: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
Pain Response Using Brief Pain Inventory-Short Form (BPI-SF) for Pain Intensity Score
Pain response was analyzed using the brief pain inventory-short form (BPI-SF).
Time frame: Baseline until the end of study (maximum duration: 1059 days)
Time to Pain Progression
Time to pain progression was defined as the time interval between the date of randomization and the date of the first documented pain progression.
Time frame: Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days)
Percentage of Participants With Symptomatic Skeletal Event (SSE)
SSE was the occurrence of a new symptomatic pathological fracture, or the use of external beam radiation to relieve bone pain, or the occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.
Time frame: Baseline until the end of study (maximum duration: 1059 days)
Time to Occurrence of Any Symptomatic Skeletal Events (SSE)
Time to SSE was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SSE, whichever is earlier.
Time frame: Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days)

Results

Posted Jun 21, 2019

Participant flow

Study conducted at 6 active centers in United States and Canada. A total of 8 participants were enrolled between 17 June 2015 to 13 Mar 2016. Total 15 participants were screened, out of which 7 were screen failures and 8 were randomized and treated in the study. Study was terminated early due to very low recruitment rate in both countries involved.

Participant flow — Overall Study
Milestone	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Started	4	4
Completed	2	2
Not completed	2	2
Withdrew: Adverse event	1	1
Withdrew: Investigator's decision	1	0
Withdrew: Study termination	0	1

Outcome measures

PrimaryRadiographic Progression-Free Survival (rPFS)

rPFS was defined as the time from randomization to the first occurrence of radiological tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or progression of bone lesions using prostate cancer working group 2 (PCWG2) criteria or death due to any cause.

Time frame:: Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)