The Effect of Metformin in Patients With Newly Diagnosed mHSPC

NCT ID: NCT04925063

Last Updated: 2021-06-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 266 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-16
• Study Completion Date: 2027-08-31

Brief Summary

The purpose of this study is to assess the effect of the addition of metformin to abiraterone on survival in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. The half the patients will receive metformin in combination with androgen deprivation therapy (ADT) and abiraterone, and the other half will receive ADT and abiraterone only.

Detailed Description

Metastatic hormone-sensitive prostate cancer (mHSPC) can be treated with androgen-deprivation therapy (ADT) alone, ADT plus abiraterone, ADT plus enzalutamide, ADT plus apalutamide, ADT plus docetaxel. However, most patients eventually progress to castration-resistant prostate cancer (CRPC) and die of the disease. Therefore, there is still a need to improve the therapeutic effect for mHSPC.

Many studies have shown that metabolic syndrome and its components are associated with increased development and progression of aggressive prostate cancer. Metformin, a common well-tolerated oral biguanide prescribed for type II diabetes, could be used to decrease the risk of prostate cancer development and improve the efficacy of treatment. Some studies reported that metformin could enhance the effectiveness of ADT, and improve recurrence-free survival, overall survival and cancer-specific survival. A prospective randomized study reported that metformin potentially lengthen time to CRPC in advanced prostate cancer patients when combined with ADT especially in those with high risk localized prostate cancer, clinically node positive and in those with low tumor volume metastatic hormone-sensitive patients.

After extensive research, there is no published results from prospective randomized trials evaluating the effect of metformin in combination with ADT and abiraterone among patients with newly diagnosed mHSPC.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin+ADT+abiraterone

Drug: Metformin The starting daily dose of metformin is 500mg once daily, to be increased to 2000mg once daily if tolerated until disease progression Drug: Abiraterone Abiraterone 1000mg once daily until disease progression

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

The starting daily dose of metformin is 500mg once daily, and add a dose of 500mg per week until the target dose of 2000mg once daily if tolerated. Metformin will be continued until disease progression.

ADT+abiraterone

Drug: Abiraterone Abiraterone 1000mg once daily until disease progression

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metformin

The starting daily dose of metformin is 500mg once daily, and add a dose of 500mg per week until the target dose of 2000mg once daily if tolerated. Metformin will be continued until disease progression.

Intervention Type: DRUG

Other Intervention Names

Metformin Hydrochloride Sustained Release Tablets

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed and newly diagnosed metastatic hormone-sensitive adenocarcinoma of the prostate without small cell carcinoma or small cell components.
• Metastatic adenocarcinoma of the prostate proved by imaging (CT/MRI and/or bone scan).
• Patient must give written informed consent before registration and prior to any trial related investigations.
• Age ≥18 years.
• Serum potassium ≥3.5mmol/ L.
• ECOG performance status 0-2
• Ongoing androgen deprivation therapy with drugs or bilateral orchiectomy, and continuous abiraterone plus prednisone.
• Patient agrees not to father a child during participation in the trial and during 3 months thereafter.
• Patient agrees not to participate other interventional trials.
• Patients are able to swallow study drug as whole tablet.

Exclusion Criteria

• Diagnosed diabetes or fasting blood-glucose ≥ 6.1mmol/L, or glycosylated hemoglobin ≥ 5.6%.
• Previous malignancy within 2 years prior to randomization, with the exception of localized non-melanoma skin cancer and Ta bladder cancer.
• Prior treatment for prostate cancer with drugs, radiotherapy and surgery, with the exception below:

• ADT within 3 months before randomization, and no evidence of progression.
• Palliative radiotherapy or surgery for metastases due to symptoms, at least 4 weeks before randomization.
• Major surgery within 4 weeks prior to randomization.
• Treatments with 5a-reductase inhibitors, estrogen, cyproterone acetate, and androgen within 4 weeks prior to randomization.
• Known or suspected Central nervous system CNS metastases or active leptomeningeal disease.
• Equivalent dosage of >5mg/day prednisone of glucocorticoids for the treatment of prostate cancer within 4 weeks prior to randomization, or treatment with glucocorticoids for other reasons.
• Prior treatment for prostate cancer with flutamide, bicalutamide, ketoconazole, abiraterone, enzalutamide, apalutamide, docetaxel chemotherapy, or other interventional drugs for prostate cancer.
• Neutrophils < 1.5 x 109/L, platelets < 75 x 109/L, hemoglobin < 100 g/L.
• ALT and AST ≥ 2.5 x ULN, bilirubin ≥ 1.5 x ULN.
• eGFR<45 ml/min/1.73m2.
• Allergic to metformin or any ingredients of this tablet.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis.
• Albumin< 30 g/L.
• Clinically significant cardiovascular disease including:

• Myocardial infarction within 6 months prior to randomization.
• Uncontrolled angina within 3 months prior to registration.
• Congestive heart failure NYHA class III or IV.
• History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes).
• History of Mobitz II second or third degree heart block without a permanent pacemaker in place.
• Systolic pressure< 86 mmHg.
• Bradycardia, heart rate<45/min.
• Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg OR diastolic blood pressure > 105 mmHg.
• ADT with or without anti-androgens more than 3 months prior to randomization.
• Prior treatment with metformin after diagnosis of prostate cancer.
• Allergic to metformin or any drugs used in this trial.
• Serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled or acute severe infection, uncontrolled diabetes).
• Active or symptomatic viral hepatitis or chronic liver disease.
• History of pituitary or adrenal dysfunction.
• Gastrointestinal disorder affecting absorption.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yonghong Li

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Yonghong Li, M.D.

Role: CONTACT

liyongh@sysucc.org.cn

86-13711376697

Zhenyu Yang, M.D.

Role: CONTACT

yangzy@sysucc.org.cn

86-13902290670

Other Identifiers

2021-FXY-078

Identifier Type: -

Identifier Source: org_study_id