Clinical trial NCT03511196: Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer
Official title: A Phase 1b Study of Adaptive Androgen Deprivation Therapy for State IV Castration Sensitive Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Stage IV Prostate Cancer
Advanced Prostate Cancer
Adenocarcinoma of the Prostate
Keywords: stage IV castration sensitive prostate cancer
advanced castration sensitive prostate cancer
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
First posted: 2018-04-27
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Adaptive Androgen Deprivation Therapy (ADT) plus Standard of Care. The purpose of this study is to develop adaptive therapy for high risk metastatic castration sensitive prostate cancer (mCSPC).

Detailed description: Investigators proposed this pilot feasibility study to use prostate specific antigen (PSA) response and testosterone level to guide the treatment with androgen deprivation therapy (ADT) \[Leuprolide, Goserelin, and Triptorelin are the most commonly used GnRH agonists for ADT\] and/or abiraterone plus prednisone. Adaptive therapy is a program of chemotherapy where the type and dosage of drug changes in an attempt to kill more of the cancer.

Abiraterone acetate with prednisone is a standard of care treatment for mCRPC (metastatic castration resistant prostate cancer). It works by interrupting the male hormone (androgen) making process in the testes, adrenal glands, and tumors. This helps to prevent the growth of tumors that need these hormones to grow.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate.
* \>75% prostate specific antigen (PSA) decline after 12 to 16 weeks of run in period with Gonadotropin-releasing Hormone (GnRH) analog abiraterone plus prednisone.
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
* Adequate organ function Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be \< 2.5 x upper limit of normal (ULN), total bilirubin less than 1.5 X ULN, estimated creatinine clearance must be \>40 mL/min, absolute neutrophil count (ANC) \> 1500/l, hemoglobin above 9 g/dl, platelet count \> 100,000/l
* Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 28 days prior to study enrollment
* Ability to give written informed consent

Exclusion Criteria:

* Prior GnRH analog with GnRH analogue for non-metastatic prostate cancer within 12 months prior to study enrollment or \>3 months of GnRH analog in the metastatic setting
* Prior treatments with TAK-700/Orteronel, ketoconazole, apalutamide or enzalutamide.
* Documented central nervous system metastases or liver metastasis
* Prior surgical castration
* Requiring opioids for cancer related pain.
* Treatment with any investigational compound within 30 days prior to the first dose of study drugs
* Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy \& have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
* Uncontrolled hypertension despite appropriate medical therapy (blood pressure of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening period). Note: Patients may be rescreened after adjustments of antihypertensive medications
* Unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade \> 2 (NCI CTCAE, version 5), New York Association Class III or IV heart failure
* Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C not contained with anti-viral therapy, life threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in investigator's opinion, potentially interfere with participation in this study.
* Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of study drugs, including difficulty swallowing tables.
* Delayed healing of wounds, ulcers, and/or bone fractures
* Inability to comply with protocol requirements

Primary outcomes:
measure: Rate of Participant Retention
timeFrame: 12 months from participant's first dose of ADT
Secondary outcomes:
measure: Median Time to Progression From the First Dose of Androgen Deprivation Therapy (ADT)
timeFrame: 12 months from participant's first dose of ADT
measure: Median Time to Radiographic Progression From the First Dose of ADT
timeFrame: 12 months from participant's first dose of ADT
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Jingsong Zhang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang J, Gallaher J, Cunningham JJ, Choi JW, Ionescu F, Chatwal MS, Jain R, Kim Y, Wang L, Brown JS, Anderson AR, Gatenby RA. A Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Cancer. Cancers (Basel). 2022 Oct 25;14(21):5225. doi: 10.3390/cancers14215225.