Addition of Enzalutamide to First Line Docetaxel for Castration Resistant Prostate Cancer

NCT02453009 | Completed Phase 2

• 1 other identifier: TN-CHEIRON
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to verify if the addition of enzalutamide to docetaxel is able to improve the disease control in first line CRPC patients.

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (1)

• Rate of patients without progression (according to guideline of Prostate Cancer Clinical Trials Working Group 2 - PCWG2)

  Rate of patients without progression (according to guideline of Prostate Cancer

  6 months after docetaxel first administration

Secondary Outcomes (11)

• Rate of objective response according to RECIST criteria

  6 months after docetaxel first administration

• Rate of biochemical response according to PCWG2

  6 months after docetaxel first administration

• Kaplan-Meier estimates of progression-free survival

  6 months after docetaxel first administration

• Kaplan-Meier estimates of overall survival

  6 months after docetaxel first administration

• Kaplan-Meier estimates of biochemical progression-free survival

  6 months after docetaxel first administration

Study Arms (2)

Arm A

EXPERIMENTAL

Docetaxel 75 mg/m² intravenously on day 1 every 3 weeks for 8 cycles, plus oral prednisone 10 mg daily for 24 weeks plus oral enzalutamide 160 mg daily for 24 weeks

Drug: Docetaxel; Drug: Prednisone; Drug: Enzalutamide

Arm B

ACTIVE COMPARATOR

Docetaxel 75 mg/m² intravenously on day 1 every 3 weeks for 8 cycles, plus oral prednisone 10 mg daily for 24 weeks

Drug: Docetaxel; Drug: Prednisone

Interventions

Docetaxel DRUG

Pharmaceutical form:solution Route of administration: intravenous

Arm A; Arm B

Prednisone DRUG

Pharmaceutical form:tablet Route of administration: oral

Arm A; Arm B

Enzalutamide DRUG

Pharmaceutical form : soft gelatin capsules Route of administration: oral

Also known as: Xtandi

Arm A

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 prostate adenocarcinoma.
• Metastatic disease.
• Progressive disease while receiving hormonal therapy or after surgical castration documented by at least one of the following:
• Increase in measurable disease (RECIST 1.1) \[15\], and/or
• Appearance of new lesions, including those on bone scan consistent with progressive prostate cancer, and/or
• Rising PSA defined as 2 sequential increases above a previous lowest reference value. Each value must be obtained at least 1 week apart. A PSA value of at least 2 ng/ml is required at study entry.
• Effective castration (serum testosterone levels ≤0.50 ng/dL) by orchiectomy and/or LHRH agonists or antagonist with or without anti-androgens.
• i. If the patient has been treated with LHRH agonists or antagonist (i.e., without orchiectomy), then this therapy should be continued.
• ii. If patients were either started on complete androgen blockade, or had a PSA response (defined by any reduction in PSA sustained for at least 3 months) after adding an antiandrogen, prior anti-androgen therapy should be stopped before randomization: at least 6 weeks for bicalutamide and nilutamide, and at least 4 weeks for flutamide, megestrol acetate and any other hormonal therapy.
• More than 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (see Appendix 2).
• Ability to fill the quality of life questionnaire
• Patient compliance and geographic proximity that allow adequate follow-up.
• Presence of signed and dated IRB-approved patient informed consent form prior to enrollment into the study.

You may not qualify if:

• Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed \>3 years ago.
• Prior treatment with abiraterone acetate and/or enzalutamide
• Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of randomization. Patients may be on biphosphonates prior to study entry.
• Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to \>30% of bone marrow.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of randomization;
• Inadequate organ and bone marrow function
• Contraindications to the use of corticosteroid treatment.
• Clinically significant cardiovascular disease
• 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.
• Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene;
• 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 chemotherapy 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 other condition which in the judgment of the investigator would place the subject at undue risk or interfere with the study.

Sponsors & Collaborators

• Santa Chiara Hospital: lead

Study Sites (1)

Santa Chiara Hospital

Trento, 38122, Italy

Location

Related Publications (1)

• Caffo O, Ortega C, Nole F, Gasparro D, Mucciarini C, Aieta M, Zagonel V, Iacovelli R, De Giorgi U, Facchini G, Veccia A, Palesandro E, Verri E, Buti S, Razzini G, Bozza G, Maruzzo M, Ciccarese C, Schepisi G, Rossetti S, Maines F, Kinspergher S, Fratino L, Ermacora P, Nicodemo M, Giordano M, Sartori D, Scapoli D, Sabbatini R, Lo Re G, Morelli F, D'Angelo A, Vittimberga I, Lippe P, Carrozza F, Messina C, Galli L, Valcamonico F, Porta C, Pappagallo G, Aglietta M. Docetaxel and prednisone with or without enzalutamide as first-line treatment in patients with metastatic castration-resistant prostate cancer: CHEIRON, a randomised phase II trial. Eur J Cancer. 2021 Sep;155:56-63. doi: 10.1016/j.ejca.2021.06.016. Epub 2021 Aug 3.

  PMID: 34358777 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Prednisone; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Orazio Caffo, MD

  Santa Chiara Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: May 25, 2015
• Study Start: October 1, 2014
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2019
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

IT (1)