Conditions: Prostate Cancer Pain
Keywords: Adenocarcinoma of the prostate Recurrent prostate cancer Stage IV prostate cancer Pain
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 22
Healthy volunteers: no

Brief summary:
Azacitidine can reverse clinical resistance to docetaxel through upregulation of Growth Arrest and DNA Damage inducible alpha (GADD45α) and other epigenetically regulated genes.

Detailed description:
Study design A phase I/II clinical trial in patients with hormone refractory metastatic prostate cancer.

Primary objective phase I component of study:

To determine a safe and potentially efficacious phase II dose of azacitidine in combination with docetaxel and prednisone that can be used for the treatment of hormone refractory metastatic prostate cancer.

Primary objective phase II component of study:

To determine the therapeutic efficacy of combined therapy of azacitidine, docetaxel, and prednisone, in the treatment of hormone refractory metastatic prostate cancer. The primary measure of therapeutic efficacy is response, defined as prostate-specific antigen (PSA) response, complete response (CR), or partial response (PR).

Secondary endpoints are toxicity, duration of response, progression-free survival, and overall survival.

Arms:
arm 1: Phase 1 Azacitidine (Aza) and Docetaxel (Doc) with dose escalation/de-escalation design, and Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim). arm 2: Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel; and Prednisone; with optional growth factor support (pegfilgrastim/filgrastim).

Interventions: intervention 1: Azacitidine intervention 2: Docetaxel intervention 3: Prednisone intervention 4: GADD45α methylation and expression analysis intervention 5: Pegfilgrastim intervention 6: Filgrastim
Intervention descriptions: intervention 1: Intravenous infusion over 30 minutes Days 1 - 5 of each 3 weekly cycle. intervention 2: Intravenous infusion over 1 hour on day 6 of each 3 weekly cycle. intervention 3: Patient will receive prednisone 5mg twice a day from Day 1 to 21 of each cycle. intervention 4: Peripheral blood samples from patients will be collected as described in section 8.1 (total of 4 blood samples). DNA will be isolated from serum, bisulfite treated and evaluated for methylation by bisulfite genomic sequencing.

Patients with accessible prostate tissue or metastases will undergo biopsy prior to treatment if they consent to do so. intervention 5: Growth factor support.Granulocyte-colony stimulating factor (G-CSF) intervention 6: Growth factor support. Granulocyte-colony stimulating factor (G-CSF)

Protocol document: