Cabazitaxel in mCRPC Patients With AR-V7 Positive Circulating Tumor Cells (CTCs)

NCT03050866 | Unknown Phase 2

• 1 other identifier: NL58639.056.16
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 9

Brief Summary

After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available. In retrospective studies, resistance has been described to two of the treatment options, enzalutamide and abiraterone, when a splice variant of the Androgen Receptor (AR-V7) is present on circulating tumor cells (CTCs). The investigators hypothesize that patients with AR-V7 positive CTCs do have a meaningful response to cabazitaxel.

Conditions

Circulating Tumor Cell; Metastatic Prostate Cancer

Keywords

Androgen Receptor; AR-V7; Predictive Factor

Outcome Measures

Primary Outcomes (1)

• PSA response

  The primary endpoint is PSA response, defined as a ≥50% PSA decline from baseline during therapy.

  12 weeks after start of treatment

Secondary Outcomes (10)

• CTC response

  9-12 weeks after start of treatment

• PSA change

  12 weeks after start of treatment

• PSA decrease

  PSA will be assessed at baseline, every 3 weeks during study treatment (before every cycle), and in case of study treatment discontinuation without progression every 3 months until progression, death, whichever comes first

• Progression free survival

  Until end of study, which is anticipated to be 4 years after inclusion of first patient. If progression is not observed during the study, data on PFS will be censored

• Overall survival

  Until end of study, which is anticipated to be 4 years after inclusion of first patient. If death is not observed during the study, data on OS will be censored at the date patient is known to be alive or at the cut-off date, whichever comes first

Study Arms (1)

Treatment

OTHER

Treatment intervention with Cabazitaxel with premedication as necessary (antihistamine, corticosteroid, H2 antagonist, antiemetic prophylaxis)

Drug: Cabazitaxel; Other: Antihistamine; Other: Corticosteroid; Other: H2 antagonist; Other: Antiemetic

Interventions

Cabazitaxel DRUG

25mg/m2 q3w

Also known as: Jevtana

Treatment

Antihistamine OTHER

As intravenous premedication (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent)

Treatment

Corticosteroid OTHER

As intravenous premedication (dexamethasone 8 mg or equivalent)

Treatment

H2 antagonist OTHER

As intravenous premedication (ranitidine or equivalent)

Also known as: histamine H2 receptors blockers

Treatment

Antiemetic OTHER

Antiemetic prophylaxis is recommended and can be given orally or intravenously if necessary

Treatment

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
• Continued androgen deprivation therapy either by luteinizing hormone-releasing hormone (LHRH) agonists/antagonists or orchiectomy.
• Serum testosterone \<50 ng/mL (1.7 nmol/L) within 21 days before prescreening.
• Age ≥18 years
• Received prior docetaxel, and experienced disease progression during or after treatment with docetaxel.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (appendix A)
• Written informed consent according to ICH-GCP (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice) before study treatment and any study specific procedures

You may not qualify if:

• Geographical, psychological or other non-medical conditions interfering with follow-up
• Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection)
• Symptomatic central nervous system (CNS) metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.
• Prior treatment with cabazitaxel
• Treatment with both abiraterone and enzalutamide in the post-docetaxel setting
• Radiotherapy to 40% or more of the bone marrow
• Known hypersensitivity to corticosteroids
• History of severe hypersensitivity reaction (≥grade 3) to docetaxel
• 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)
• Concomitant vaccination with yellow fever vaccine
• Abnormal liver functions
• Abnormal hematological blood counts

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Sanofi: collaborator

Study Sites (9)

Reinier de Graaf Groep

Delft, Netherlands

Location

Admiraal de Ruyter Ziekenhuis

Flushing, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Franciscus Gasthuis en Vlietland

Rotterdam, Netherlands

Location

Maasstad Ziekenhuis

Rotterdam, Netherlands

Location

Medisch Centrum Haaglanden

The Hague, Netherlands

Location

Tweesteden Ziekenhuid

Tilburg, Netherlands

Location

MeSH Terms

Conditions

Neoplastic Cells, Circulating; Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

cabazitaxel; Histamine Antagonists; Adrenal Cortex Hormones; Histamine H2 Antagonists; Antiemetics

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Autonomic Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses; Gastrointestinal Agents

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 13, 2017
• Study Start: February 21, 2017
• Primary Completion: January 1, 2022
• Study Completion: August 19, 2022
• Last Updated: August 20, 2021

Record last verified: 2021-08

Locations

NL (9)