A Phase I/II Study of Azacitidine, Docetaxel, and Prednisone for Metastatic Prostate Cancer Patients

• Status: Terminated
• Trial end date: 2015-06-01
• Target enrollment: 0
• Participant gender: Male

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Miami
• Treatments: Azacitidine; Docetaxel; Lenograstim; Mitogens; Prednisone

Criteria

INCLUSION CRITERIA:

• Patient who had histologically confirmed adenocarcinoma of the prostate.

• Patient must have radiologically documented metastatic disease.

• Patients should have received at least 12 weeks of docetaxel chemotherapy or a cumulative docetaxel dose of 300 mg/m2 and have disease progression on docetaxel-based therapy. Patients must have progressed after prior hormonal therapy (e.g. medical or surgical castration) as defined by a castrate level of testosterone (less than 50 ng/mL). If patient underwent medical castration, it must be continued during the study.

• Progressive disease may be documented by:

• Non-measurable disease:

• Serum PSA progression defined as a rise in at least 2 consecutive serum PSA values, each obtained at least 1 week apart and an absolute value greater than 2.0 ng/ml or,

• Appearance of two or more new lesions on bone scan.

• Patients with treated epidural lesions and no other epidural progression will be eligible.

• Measurable disease

• Documented progression of disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria demonstrating at least one visceral or soft tissue metastatic lesion (including new lesion).

• Nodal or visceral progression will be sufficient for trial entry independent of PSA

• Only lymph nodes ≥ 2 cm in diameter will be used to assess for a change in size.

• Previously irradiated lesions, primary prostatic lesion, and bone lesions will be considered non-measurable disease.

• Patient is 18 years or older.

• Patient had a Karnofsky Performance Status (KPS) of at least 70% or Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2.

• Life expectancy of > 6 months.

• Patient with adequate organ function as defined as

• Absolute Neutrophils Count greater than 1500 cells/mm3

• Platelets greater than 100,000 cells/mm3

• Hemoglobin greater than 8 g/dL,

• Adequate liver function as documented by:

• Total Bilirubinlaboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.

• AST and ALTthe two values (AST or ALT) should be used.)

• Serum creatinine
• Male patient must be willing to use an acceptable barrier method for contraception; and must agree not to father a child whilst receiving treatment with Azacitidine and up to six months after last dose.

• Patients may have a history of prior malignancy (≥ 5 years prior) provided that the patient is currently disease free and off all therapy for that malignancy. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

• Patients must be informed of the investigational nature of the treatment and must give signed written and informed consent.

EXCLUSION CRITERIA:

• Patients who have received strontium 89 (metastron®), Samarium 153 (quadramet®) radiation therapy within 8 weeks of enrollment.

• Evidence of significant active infection during screening for eligibility.

• Patients who have had a psychiatric illness that could potentially interfere with completion of treatment according to protocol.

• Patients who had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. There is no wash-out period for patients who received Zytiga.

• Patient who had brain metastases.

• Patient who had history of allergic reactions attributed to compound or similar chemical or biological composition to azacitidine (Vidaza®) or docetaxel or other drugs formulated with polysorbate 80 or mannitol.

• Patient had major surgical procedure within 28 days before Day 1 of treatment.

• Hepatic malignancy.