Investigation of Metformin in Patients With Castration Resistant Prostate Cancer in Combination With Enzalutamide vs. Enzalutamide Alone

NCT02640534 | Terminated Phase 2

• 1 other identifier: SAKK 08/14 - IMPROVE
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 16

Brief Summary

The purpose of this trial is to test if the combination of enzalutamide and metformin in patients with castration resistant prostate cancer CRPC progressing on androgen deprivation therapy ADT is more effective compared to enzalutamide alone. The half of the patients will receive the experimental treatment combination, enzalutamide and metformin, while the other half will receive enzalutamide alone.

Conditions

Cancer of the Prostate; Prostate Cancer

Keywords

Prostate cancer; Cancer of the prostate; Metformin; Enzalutamide; Xtandi; castration resistant prostate cancer; phase II; Androgen deprivation therapy

Outcome Measures

Primary Outcomes (1)

• Disease control (DC)

  The primary endpoint of the trial is disease control (DC) at 15 months.

  at 15 months

Secondary Outcomes (4)

• Overall response (OR)

  at 15 months

• Event-free survival (EFS)

  at 15 months

• Adverse events (AEs)

  at 15 months

• Overall survival (OS)

  at 15 months

Study Arms (2)

Enzalutamide + Metformin

EXPERIMENTAL

Enzalutamide 160 mg od + metformin 850 mg bid until disease progression

Drug: Enzalutamide; Drug: Metformin

Enzalutamide

ACTIVE COMPARATOR

Enzalutamide 160 mg od until disease progression

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Enzalutamide 160 mg od until disease progression

Enzalutamide; Enzalutamide + Metformin

Metformin DRUG

850 mg bid until disease progression

Enzalutamide + Metformin

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to ICH/GCP regulations before registration and prior to any trial-related investigations
• Histologically or cytological confirmed adenocarcinoma of the prostate without small cell carcinoma or small cell components
• Asymptomatic or minimally symptomatic patients in relation to disease
• Metastatic adenocarcinoma of the prostate documented by imaging (CT/MRI and/or bone scan)
• Ongoing androgen deprivation therapy with Gonadotropin-releasing hormone GnRH analogues or bilateral orchiectomy (i.e. surgical or medical castration)
• Total testosterone levels ≤ 1.7 nmol/L (corresponding to ≤ 50 ng/dL)
• Tumor progression at the time of registration, defined as per protocol.
• Completed baseline QoL and pain questionnaires
• Male patients ≥ 18 years
• WHO performance status 0-2
• Adequate hematologic values: hemoglobin ≥ 90 g/L, neutrophils ≥ 1.0 x 109/L, platelets ≥ 75 x 109/L
• Adequate hepatic function: ALT and AST ≤ 2.5 x ULN, bilirubin ≤ 1.5 x ULN (exception if Gilbert's syndrome ≤ 2.5 x ULN)
• Adequate renal function: calculated creatinine clearance ≥ 50 mL/min, according to the formula of Cockcroft-Gault
• Patient is able to swallow the trial drugs and comply with trial requirements
• Patient agrees not to father a child during participation in the trial and during 3 months thereafter

You may not qualify if:

• Known or suspected Central nervous system CNS metastases or active leptomeningeal disease
• Previous malignancy within 2 years prior to registration, with the exception of localized non-melanoma skin cancer and Ta and Tis bladder cancer
• Prior treatment for prostate cancer with
• novel endocrine agents (including abiraterone acetate, enzalutamide, TAK-700, TAK-683, TAK-448, VT464, darolutamide, apalutamide),
• radioisotopes,
• TKI and other small molecules,
• immunotherapy,
• chemotherapy (with the exception of docetaxel chemotherapy in hormone sensitive prostate cancer)
• Treatment with experimental drugs or treatment within a clinical trial within 30 days prior to registration (except the clinical trial SAKK 96/12, PEACE-4 and/or the biobank project SAKK 63/12)
• Clinically significant cardiovascular disease including:
• Myocardial infarction within 6 months prior to registration,
• Uncontrolled angina within 3 months prior to registration,
• Congestive heart failure NYHA class III or IV,
• QTc interval \> 480 ms,
• History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes),

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (16)

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, 6500, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Spital Thurgau AG

Frauenfeld, CH-8500, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

CCAC Lausanne

Lausanne, 1004, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Hôpital du Valais

Martigny-Ville, 1920, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Hôpital du Valais

Sion, 1951, Switzerland

Location

Bürgerspital Solothurn

Solothurn, CH-4500, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Metformin

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)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Christian Rothermundt, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 22, 2015
• First Posted: December 29, 2015
• Study Start: June 10, 2016
• Primary Completion: July 1, 2022
• Study Completion: March 16, 2023
• Last Updated: June 27, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (16)