Optimal Sequencing of Treatment Options for Poor Risk mCRPC Previously Treated With Docetaxel

NCT03295565 | Completed Phase 2

• 1 other identifier: m16OST
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 19

Brief Summary

Rationale: The aim of this study is to identify the optimal second line treatment option for patients with a poor prognosis metastasized Castration Resistant Prostate Cancer (mCRPC) with respect to Clinical Benefit Rate (CBR) rate and quality of life. Objective: The primary endpoint is CBR in mCRPC patients with poor prognostic features and previously treated with docetaxel, randomized between cabazitaxel (Arm A) and novel hormonal agents (abiraterone OR enzalutamide) as second-line therapy (Arm B). Intervention: Patients in Arm A will receive cabazitaxel and prednisone and patients in Arm B will receive abiraterone and prednisone OR enzalutamide. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment regimens evaluated in this trial are used in common mCRPC treatment practice and are reimbursed. Risk of side effects or death as a result of treatment is not affected by the trial design. At baseline, prior to each treatment cycle and at end of treatment, patients are requested to visit the out-patient clinic, where a physical exam will be performed in combination with vena puncture for blood analysis. Radiological evaluation will be performed at base line, after 3 months of treatment and at end of treatment. All above mentioned interventions can be considered as standard practice. Patients are requested to fill out QoL and pain/analgesic use questionnaires at base line, prior to each cycle and at end of treatment.

Conditions

Prostate Cancer Metastatic; Metastasis

Keywords

Sequencing; cabazitaxel; abiraterone; enzalutamide; clinical benefit rate; docetaxel; second line treatment

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate

  • To assess the Clinical Benefit Rate (CBR) in patients with mCRPC and poor prognostic factors treated with cabazitaxel (Arm A) or novel hormonal agents (abiraterone OR enzalutamide) as second-line therapy (Arm B) who have been treated with docetaxel.

  From start treatment until 12 weeks of treatment

Secondary Outcomes (12)

• Comparing clinical benefit rate in arm A and arm B

  From start treatment until 12 weeks of treatment

• Duration of treatment

  for each patient; until end of treatment (for Arm A max 30 weeks, for Arm B max 24 months)

• Progression free survival

  for each patient; until progression or through study completion (max 24 months)

• Overall survival

  for each patient; until death or end of trial (max 24 months)

• (serious) adverse events according to the ctcae v4.03: number of incidents, number of participants with (S)AE's

  for each patient: until 28 days after the last treatment

Other Outcomes (3)

• Exploratory objectives; neutrophil to lymphocyte ratio

  For each patient: until the end of treatment, Arm A max 30 weeks, Arm B max 24 months

• Exploratory objectives; number of mutations in 73 genes from cell-free DNA

  For each patient: until the end of treatment, Arm A max 30 weeks, Arm B max 24 months

• Exploratory objectives; epigenetics-based biomarker discovery using cfDNA

  For each patient: until end of treatment (max 24 months)

Study Arms (2)

A: Cabazitaxel

ACTIVE COMPARATOR

Cabazitaxel 25mg/m2 IV, once every 3 weeks

Drug: Cabazitaxel

B: Abiraterone OR Enzalutamide

ACTIVE COMPARATOR

At physician's discretion: Abiraterone 1000mg oral, taken daily Prednisone 5mg oral, 2 times a day OR Enzalutamide 160mg oral taken daily

Drug: Abiraterone; Drug: Enzalutamide

Interventions

Cabazitaxel DRUG

Cabazitaxel 25mg/m2 IV, once every 3 weeks

Also known as: No other intervention names

A: Cabazitaxel

Abiraterone DRUG

Abiraterone 1000mg oral, taken daily + Prednisone 5mg oral, 2 times a day

Also known as: No other intervention names

B: Abiraterone OR Enzalutamide

Enzalutamide DRUG

Enzalutamide 160mg oral taken daily

Also known as: No other intervention names

B: Abiraterone OR Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of prostate adenocarcinoma.
• Able and willing to provide informed consent and to comply with the study procedures
• Age ≥18
• Evidence of bone, visceral and/or lymph node metastases on bone scan, CT-scan or MRI.
• Must have received at least one prior regimen of docetaxel treatment for at least 12 weeks (four courses) and no other prostate cancer treatments between docetaxel and randomization, other than prednisone.
• Continued androgen deprivation therapy either by luteinizing hormone release hormone (LHRH) agonist/ antagonist or orchiectomy.
• Treatment with curative intent is not an option and patient has an indication for systemic treatment as judged by the medical care provider
• Evidence of progressive metastatic disease by PSA progression (Prostate Cancer Working Group 3 (PCWG3) criteria20: at least 2 rises at a minimum of 1-week intervals. The first PSA value must be ≥ 2 ng/ml) and/or radiological progression as evaluated by chest, abdominal, or pelvic CT/MRI scan and/or bone scan within 28 days of registration (see Appendix III)
• Poor prognosis disease as defined by any of the following:
• The presence of liver metastases AND/OR
• Development of castration-resistance within 12 months of orchiectomy or commencement of LHRH antagonist/agonist for metastatic disease AND/OR
• Progressive disease during docetaxel treatment or \<6 months after completion of docetaxel treatment
• World Health Organization Performance Status (WHO PS) 0-2.
• Serum testosterone \< 50 ng/dL (\< 1.7 nmol/L) within 28 days before treatment group allocation
• At least 21 days have passed since completing radiotherapy (exception for a single fraction of ≤ 800 centi-Gray (cGy) to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit: at least 7 days prior to randomization).

You may not qualify if:

• Histologic evidence of small cell/neuroendocrine prostate cancer
• Any treatment other than prednisone between docetaxel and cabazitaxel/abiraterone OR enzalutamide sequence
• Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus).
• History of severe hypersensitivity reaction (≥ grade 3) to docetaxel, abiraterone or enzalutamide (whichever applies).
• History of severe hypersensitivity reaction (≥ grade 3) to polysorbate 80 containing drugs.
• Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments).
• Patients who have a concurrent yellow fever vaccination (several weeks before start of treatment) must be excluded.
• Dementia, altered mental status, or any psychiatric condition, if this is in conflict with the study.
• Unable to swallow a whole tablet or capsule
• Contraindications to the use of corticosteroid treatment
• Symptomatic peripheral neuropathy Grade ≥2 (see Appendix VIII).
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured and needing no subsequent therapy.
• Inadequate organ and bone marrow function as evidenced by:
• Hemoglobin \<10.0 g/dL
• Absolute neutrophil count \<1.5 x 109/L

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (19)

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

Location

Bovenij ziekenhuis

Amsterdam, Netherlands

Location

Rode Kruis Ziekenhuis

Beverwijk, 1940 EB, Netherlands

Location

Tergooi Ziekenhuizen

Blaricum, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Slngeland Ziekenhuis

Doetinchem, Netherlands

Location

Ziekenhuisgroep Twente

Hengelo, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, Netherlands

Location

Dijklander ziekenhuis

Hoorn, Netherlands

Location

Medisch Centrum leeuwarden

Leeuwarden, Netherlands

Location

Academisch medisch centrum Maastricht

Maastricht, Netherlands

Location

Sint Antonius ziekenhuis

Nieuwegein, Netherlands

Location

Franciscus Gasthuis-Vlietland

Rotterdam, Netherlands

Location

Zorgsaam Ziekenhuis

Terneuzen, Netherlands

Location

Haga Ziekenhuis

The Hague, Netherlands

Location

Diakonessenhuis

Utrecht, Netherlands

Location

Universitair medisch centrum Utrecht

Utrecht, Netherlands

Location

Viecuri medisch centrum Noord-Limburg

Venlo, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

cabazitaxel; abiraterone; enzalutamide

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, open label, Phase IIB trial

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: September 28, 2017
• Study Start: May 7, 2017
• Primary Completion: December 16, 2020
• Study Completion: March 2, 2022
• Last Updated: April 15, 2022

Record last verified: 2022-04

Locations

NL (19)