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

NCT ID: NCT00503984

Last Updated: 2016-06-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2015-06-30

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.

Conditions

Prostate Cancer; Pain

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 - Aza + Doc

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).

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Intravenous infusion over 30 minutes Days 1 - 5 of each 3 weekly cycle.

Docetaxel

Intervention Type: DRUG

Intravenous infusion over 1 hour on day 6 of each 3 weekly cycle.

Prednisone

Intervention Type: DRUG

Patient will receive prednisone 5mg twice a day from Day 1 to 21 of each cycle.

GADD45α methylation and expression analysis

Intervention Type: GENETIC

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.

Pegfilgrastim

Intervention Type: DRUG

Growth factor support.Granulocyte-colony stimulating factor (G-CSF)

Filgrastim

Intervention Type: DRUG

Growth factor support. Granulocyte-colony stimulating factor (G-CSF)

Phase 2 - Aza + Doc RPTD

Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel; and Prednisone; with optional growth factor support (pegfilgrastim/filgrastim).

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Intravenous infusion over 30 minutes Days 1 - 5 of each 3 weekly cycle.

Docetaxel

Intervention Type: DRUG

Intravenous infusion over 1 hour on day 6 of each 3 weekly cycle.

Prednisone

Intervention Type: DRUG

Patient will receive prednisone 5mg twice a day from Day 1 to 21 of each cycle.

Pegfilgrastim

Intervention Type: DRUG

Growth factor support.Granulocyte-colony stimulating factor (G-CSF)

Filgrastim

Intervention Type: DRUG

Growth factor support. Granulocyte-colony stimulating factor (G-CSF)

Interventions

Azacitidine

Intravenous infusion over 30 minutes Days 1 - 5 of each 3 weekly cycle.

Intervention Type: DRUG

Docetaxel

Intravenous infusion over 1 hour on day 6 of each 3 weekly cycle.

Intervention Type: DRUG

Prednisone

Patient will receive prednisone 5mg twice a day from Day 1 to 21 of each cycle.

Intervention Type: DRUG

GADD45α methylation and expression analysis

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 Type: GENETIC

Pegfilgrastim

Growth factor support.Granulocyte-colony stimulating factor (G-CSF)

Intervention Type: DRUG

Filgrastim

Growth factor support. Granulocyte-colony stimulating factor (G-CSF)

Intervention Type: DRUG

Other Intervention Names

Vidaza®; Taxotere®; Neulasta; Neupogen

Eligibility 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 Bilirubin </= 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
• AST and ALT </= 2.5 ULN. (In determining eligibility the more abnormal of the two values (AST or ALT) should be used.)
• Serum creatinine </= 2.0 mg/dl or </= 1.5 x institutional upper limit of normal.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Rakesh Singal

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rakesh Singal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami Sylvester Comprehensive Cancer Center

Locations

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Countries

United States

References

Singal R, Ramachandran K, Gordian E, Quintero C, Zhao W, Reis IM. Phase I/II study of azacitidine, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy. Clin Genitourin Cancer. 2015 Feb;13(1):22-31. doi: 10.1016/j.clgc.2014.07.008. Epub 2014 Aug 1.

Reference Type: BACKGROUND

PMID: 25178642 (View on PubMed)

Other Identifiers

SCCC-2006080

Identifier Type: OTHER

Identifier Source: secondary_id

WIRB-20070344

Identifier Type: OTHER

Identifier Source: secondary_id

20140376

Identifier Type: OTHER

Identifier Source: secondary_id

20061143

Identifier Type: -

Identifier Source: org_study_id