1911GCCC: Galeterone or Galeterone With Gemcitabine for Patients With Metastatic Pancreatic Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
Assess the effectiveness of galeterone in advanced pancreatic adenocarcinoma

Detailed Description
-----------------
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of galeterone, an investigational drug, in pancreatic cancer. The FDA (the U.S. Food and Drug Administration) has not approved galeterone for pancreatic cancer. Galeterone is an androgen receptor inhibitor that showed anti-cancer activity in pancreatic cancer in research lab. In this study, the investigator is interested in evaluating galeterone alone or in combination with chemotherapy in treating pancreatic cancer.

Official Title
-----------------
1911GCCC:Two Parallel, Single-arm, Open Label, Phase 2 Trials of Galeterone Alone or Galeterone Combined With Gemcitabine for Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Standard Chemotherapy

Conditions
-----------------
Advanced Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: galeterone
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to understand and willingness to sign a written informed consent document Agree to comply with the study requirements and agrees to come to the clinic/hospital for required study visits 18 years of age or order Histologic or cytologic diagnosis of pancreatic adenocarcinoma Measurable metastatic disease documented by CT/MRI at least 1cm in greatest dimension Have received 2 lines of prior systemic therapy; those patients must demonstrate continued disease progression (RECIST 1.1) and must not have received chemotherapy for at least 4 weeks prior to trial assignment; ECOG performance status must be 0-2 (Appendix A). All participants (male and female) with reproductive potential must practice an effective method of contraception while on this study in order to minimize risks to fetuses. Men and women of all ethnic groups are eligible for this trial. Able to swallow up to six pills and retain oral medication Expected life expectancy of more than 12 weeks. Patient has adequate bone marrow function as demonstrated by the following blood counts at Baseline (obtained ≤14 days prior to randomization): Absolute neutrophil count (ANC) ≥1.5 × 109/L; Platelet count ≥100,000/mm3 (100 × 109/L); Hemoglobin (Hgb) ≥ 8 g/dL. Patient has adequate organ functions at baseline (obtained ≤14 days prior to randomization): AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal range (ULN), Total bilirubin ≤ 1.2mg/dl Serum creatinine within normal limits or calculated clearance ≥50 mL/min. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockroft-Gault formula). For patients with a Body Mass Index (BMI) >30 kg/m2, adjusted body weight should be used instead. Patients with well controlled oligo brain metastasis are eligible Ability to understand and willingness to sign a written informed consent document. Agree to comply with the study requirements and agrees to come to the clinic/hospital for required study visits. 18 years of age or order. Histologic or cytologic diagnosis of stage IV pancreatic adenocarcinoma. Measurable disease per RECIST 1.1 criteria. Have received 2 lines of prior systemic therapy; those patients must demonstrate continued disease progression (RECIST 1.1) and must not have received chemotherapy for at least 4 weeks prior to trial assignment. ECOG performance status must be 0-2 (Appendix A). All participants (male and female) with reproductive potential must agree to be abstinent or practice an effective method of contraception while on this study in order to minimize risks to fetuses. Men and women of all ethnic groups are eligible for this trial. Able to swallow up to six pills and retain oral medication. Expected life expectancy of more than 12 weeks. Exclusion Criteria: Participation in another clinical trial involving experimental therapy for pancreatic adenocarcinoma within 4 weeks prior to enrollment or simultaneous participation in a study involving investigational treatment. Prior anti-cancer therapy: Prior treatment with galeterone, or anti-androgens. Prior radiation therapy within 4 weeks (if single fraction of radiotherapy within 2 weeks). Concurrent use of other anti-cancer agents. Major surgery within 4 weeks prior to randomization. The following medical conditions: New York Heart Association Class III or IV congestive heart failure. Myocardial infarction/unstable angina (within the 6 months prior to randomization). History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia). History of long QT syndrome, Mobitz II second or third degree heart block without a permanent pacemaker in place. Bradycardia as defined by heart rate of <50 beats/minute at Screening ECG. History of chronic or active Hepatitis B or Hepatitis C or other known chronic liver disease. Patients recovered from hepatitis are not excluded from the study. Known human immunodeficiency virus (HIV) infection. Uncontrolled hypertension (defined as systolic blood pressure > 170 mmHg or diastolic blood pressure of > 105 mmHg measured on at least two occasions, two weeks apart) despite acceptable anti-hypertension therapy. Hypotension (defined as systolic blood pressure <90 mmHg). History of adrenal insufficiency or hyperaldosteronism. Gastrointestinal disorders or gastric bypass surgery, with the exception of pancreatic cancer and its complications, including lap bands that could interfere with the absorption of galeterone. Serious active infections requiring systemic treatment or nonmalignant medical illnesses that are uncontrolled. History of seizure or any condition or concomitant use of any medication that may predispose to seizure or lower the seizure threshold. History of loss of consciousness or transient ischemic attack within 12 months of randomization. History of (in the past 5 years) other malignancy, other than curatively treated nonmelanomatous skin cancer and superficial transitional cell carcinoma of the bladder. Cranial/spinal epidural disease. The patient has known allergy to any of the treatment components. Any physical or mental condition or social situation that, in the opinion of the Investigator, may interfere with the patient's ability to comply with the trial procedures, confound the ability to interpret data from the study or places the patient at unacceptable risk if he participates in this study. Current alcohol abuse or illicit drug use. Since the teratogenic potential of this combination is currently unknown, females who are pregnant or lactating are excluded. Females at reproductive age must have a negative urine pregnancy test prior to entry to this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 parallel arm phase II study of galeterone alone or galeterone with gemcitabine in advanced pancreatic cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: galeterone<br>galeterone orally once daily | Drug: galeterone<br>* Therapeutic<br>|
| Experimental: galeterone+gemcitabine<br>daily dose galeterone and weekly dose of gemcitabine | Drug: galeterone<br>* Therapeutic<br>Drug: Gemcitabine<br>* Therapeutic<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | number of patients whose disease shrink during treatment | 8 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | time for galeterone to control the disease | From date of randomization until the date of first documented progression, assessed up to 100 months | 
| overall survival | total life expectancy | From date of randomization until the date of death from any cause, assessed up to 100 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pancreatic cancer