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

CHemotherapy Plus Enzalutamide In First Line Therapy for Castration Resistant prOstate caNcer

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.

Study Overview

• Status: Unknown
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Docetaxel; Drug: Prednisone; Drug: Enzalutamide

Detailed Description

CHEIRON trial is a phase II randomized study comparing docetaxel plus enzalutamide to docetaxel alone as first line for castration resistant prostate cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 232
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Trento, Italy, 38122
    • Recruiting
    • Santa Chiara Hospital
    • Contact: Orazio Caffo, MD; Phone Number: +390461902478; Email: orazio.caffo@apss.tn.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Histologically- or cytologically-confirmed prostate adenocarcinoma.
2. Metastatic disease.

3. 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.

4. More than 18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status <2 (see Appendix 2).
6. Ability to fill the quality of life questionnaire
7. Patient compliance and geographic proximity that allow adequate follow-up.
8. Presence of signed and dated IRB-approved patient informed consent form prior to enrollment into the study.

Exclusion Criteria:

1. Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago.
2. Prior treatment with abiraterone acetate and/or enzalutamide
3. 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.
4. Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
5. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
6. 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;
7. Inadequate organ and bone marrow function
8. Contraindications to the use of corticosteroid treatment.
9. Clinically significant cardiovascular disease
10. 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.
11. Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene;
12. 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.
13. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
14. Any other condition which in the judgment of the investigator would place the subject at undue risk or interfere with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; Pharmaceutical form:solution Route of administration: intravenous; Drug: Prednisone; Pharmaceutical form:tablet Route of administration: oral; Drug: Enzalutamide; Pharmaceutical form : soft gelatin capsules Route of administration: oral; Other Names: Xtandi
Active Comparator: Arm B; 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; Pharmaceutical form:solution Route of administration: intravenous; Drug: Prednisone; Pharmaceutical form:tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of patients without progression (according to guideline of Prostate Cancer Clinical Trials Working Group 2 - PCWG2)	6 months after docetaxel first administration

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Rate of treatment-related mortality	6 months after docetaxel first administration
Rate of toxicity-related protocol withdrawal	6 months after docetaxel first administration
Scales of brief pain inventory (BPI)	6 months after docetaxel first administration
Analgesic score	6 months after docetaxel first administration
Functional scales and items of FACT - P questionnaire	6 months after docetaxel first administration
Type and grade of any adverse reaction to treatment, according to CTC-AE v. 4.03	6 months after docetaxel first administration

Collaborators and Investigators

• Sponsor: Santa Chiara Hospital
• Investigators: Study Chair: Orazio Caffo, MD, Santa Chiara Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): September 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: May 19, 2015
• First Submitted That Met QC Criteria: May 22, 2015
• First Posted (Estimate): May 25, 2015

Study Record Updates

• Last Update Posted (Estimate): May 25, 2015
• Last Update Submitted That Met QC Criteria: May 22, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: TN-CHEIRON