A Phase I/II Study of Azacitidine, Docetaxel, and Prednisone for Metastatic Prostate Cancer Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Azacitidine
Intravenous infusion over 30 minutes Days 1 - 5 of each 3 weekly cycle.
Other Names:
Drug: Docetaxel
Intravenous infusion over 1 hour on day 6 of each 3 weekly cycle.
Other Names:
Drug: Prednisone
Patient will receive prednisone 5mg twice a day from Day 1 to 21 of each cycle.
Genetic: 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.
Drug: Pegfilgrastim
Growth factor support.Granulocyte-colony stimulating factor (G-CSF)
Other Names:
Drug: Filgrastim
Growth factor support. Granulocyte-colony stimulating factor (G-CSF)
Other Names:
|
| Experimental: Phase 2 - Aza + Doc RPTD Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel; and Prednisone; with optional growth factor support (pegfilgrastim/filgrastim). |
Drug: Azacitidine
Intravenous infusion over 30 minutes Days 1 - 5 of each 3 weekly cycle.
Other Names:
Drug: Docetaxel
Intravenous infusion over 1 hour on day 6 of each 3 weekly cycle.
Other Names:
Drug: Prednisone
Patient will receive prednisone 5mg twice a day from Day 1 to 21 of each cycle.
Drug: Pegfilgrastim
Growth factor support.Granulocyte-colony stimulating factor (G-CSF)
Other Names:
Drug: Filgrastim
Growth factor support. Granulocyte-colony stimulating factor (G-CSF)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Azacitidine and Docetaxel) [Up to 1.5 years]
Determination of 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.
- Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Prednisone) [Up to 1.5 years]
Determination of 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.
- Number of Participants Achieving Prostate-specific Antigen (PSA) Response. [Up to 4.5 years.]
Number of participants achieving prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 1 (PCWG1) criteria. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks.
- Number of Participants Achieving Complete Response (CR) or Partial Response (CR) to Protocol Therapy. [Up to 4.5 years]
Number of participants achieving Complete Response (CR) or Partial Response to protocol therapy according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 Criteria. Per RECIST 1.0 for target lesions and assessed by MRI: "Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; "
Secondary Outcome Measures
- Duration of Response [Up to 4.5 years.]
Length of time from the date of first observation of complete response (CR) or partial response (PR) to the date of first observation of disease progression, according to prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 1 (PCWG1) criteria. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks.
- Progression-Free Survival (PFS) [Up to 4.5 years]
The time from the date of start of treatment until the first documented or confirmed disease progression, or death related to prostate cancer, whichever is earlier.
- Overall Survival (OS) [Up to 4.5 years.]
The time from the date of initiation of study treatment until date of death from any cause.
- Number of Participants Experiencing Adverse Events After Beginning Protocol Therapy. [Up to 4.5 years]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Miami Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
Sponsors and Collaborators
- University of Miami
Investigators
- Principal Investigator: Rakesh Singal, MD, University of Miami Sylvester Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
- 20061143
- SCCC-2006080
- WIRB-20070344
- 20140376
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase 1: Level 1 - 75 Aza + 60 Doc | Phase 1: Level 2 - 75 Aza + 75 Doc | Phase 1: Level 3 - 100 Aza + 75 Doc | Phase 1: Level 4 - 150 Aza + 75 Doc | Phase 2 - Aza + Doc Initial RPTD | Phase 2 - Aza + Doc Reduced RPTD |
|---|---|---|---|---|---|---|
| Arm/Group Description | All Phase 1 participants who received at least one dose starting at the Level 1 dose combination of 75 mg/m^2 of Azacitidine (Aza), 60 mg/m^2 of Docetaxel (Doc) and 5mg of Prednisone. | All Phase 1 participants who received at least one dose starting at the Level 2 dose combination of 75 mg/m^2 of Azacitidine (Aza), 75 mg/m^2 of Docetaxel (Doc) and 5mg of Prednisone. | All Phase 1 participants who received at least one dose starting at the Level 3 dose combination of 100 mg/m^2 of Azacitidine (Aza), 75 mg/m^2 of Docetaxel (Doc) and 5mg of Prednisone. | All Phase 1 participants who received at least one dose starting at the Level 4 dose combination of 150 mg/m^2 of Azacitidine (Aza), 75 mg/m^2 of Docetaxel (Doc) and 5 mg of Prednisone. | All Phase 2 participants who received at least one dose of the combination of Azacitidine and Docetaxel with 5 mg of Prednisone at the recommended phase two dose level (RPTD). | All Phase 2 participants who received at least one reduced dose of the combination of Azacitidine and Docetaxel with 5 mg of Prednisone at the recommended phase two dose level (RPTD). |
| Period Title: Overall Study | ||||||
| STARTED | 3 | 3 | 3 | 6 | 6 | 1 |
| COMPLETED | 3 | 1 | 3 | 6 | 5 | 1 |
| NOT COMPLETED | 0 | 2 | 0 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase 1 | Phase 2 | Total |
|---|---|---|---|
| Arm/Group Description | All Phase 1 participants who received at least one dose of the combination of Azacitidine (Aza) and Docetaxel (Doc) and 5mg of Prednisone at one of the starting dose levels: Level 1: 75 mg/m2 Aza + 60 mg/m2 Doc Level 2: 75 mg/m2 Aza + 75 mg/m2 Doc Level 3: 100 mg/m2 Aza + 75 mg/m2 Doc Level 4: 150 mg/m2 Aza + 75 mg/m2 Doc | All Phase 2 participants who received at least one dose of the combination of Azacitidine and Docetaxel with 5 mg of Prednisone at the recommended phase two dose level (RPTD). | Total of all reporting groups |
| Overall Participants | 15 | 7 | 22 |
| Age, Customized (participants) [Number] | |||
| < 60 years |
3
20%
|
1
14.3%
|
4
18.2%
|
| 60 - 69 years |
8
53.3%
|
3
42.9%
|
11
50%
|
| >= 70 years |
4
26.7%
|
3
42.9%
|
7
31.8%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
15
100%
|
7
100%
|
22
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
5
33.3%
|
1
14.3%
|
6
27.3%
|
| Not Hispanic or Latino |
10
66.7%
|
6
85.7%
|
16
72.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
4
26.7%
|
1
14.3%
|
5
22.7%
|
| White |
11
73.3%
|
6
85.7%
|
17
77.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
15
100%
|
7
100%
|
22
100%
|
Outcome Measures
| Title | Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Azacitidine and Docetaxel) |
|---|---|
| Description | Determination of 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. |
| Time Frame | Up to 1.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants enrolled in the Phase 1 portion of the study. The initial RPTD was 150 mg/m2 Azacitidine + 75 mg/m2 Docetaxel, with 5mg of Prednisone. However, due to the death of one patient, the Data and Safety Monitoring Board (DSMB) recommended that the RPTD be reduced to 75 mg/m2 Azacitidine + 75 mg/m2 Docetaxel, with 5mg of Prednisone. |
| Arm/Group Title | Phase 1 - Aza + Doc |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 15 |
| Initial RPTD Azacitidine (mg/m2) |
150
|
| Initial RPTD Docetaxel (mg/m2) |
75
|
| Reduced RPTD Azacitidine (mg/m2) |
75
|
| Reduced RPTD Docetaxel (mg/m2) |
75
|
| Title | Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Prednisone) |
|---|---|
| Description | Determination of 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. |
| Time Frame | Up to 1.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants enrolled in the Phase 1 portion of the study. The initial RPTD was 150 mg/m2 Azacitidine + 75 mg/m2 Docetaxel, with 5mg of Prednisone. However, due to the death of one patient, the Data and Safety Monitoring Board (DSMB) recommended that the RPTD be reduced to 75 mg/m2 Azacitidine + 75 mg/m2 Docetaxel, with 5mg of Prednisone. |
| Arm/Group Title | Phase 1 - Aza + Doc |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 15 |
| Initial RPTD Prednisone (mg) |
5
|
| Reduced RPTD Prednisone (mg) |
5
|
| Title | Number of Participants Achieving Prostate-specific Antigen (PSA) Response. |
|---|---|
| Description | Number of participants achieving prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 1 (PCWG1) criteria. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks. |
| Time Frame | Up to 4.5 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Of the 22 participants enrolled, only 19 were evaluable because they completed 2 or more cycles of protocol therapy. |
| Arm/Group Title | Phase 1: Level 1 - 75 Aza + 60 Doc | Phase 1: Level 2 - 75 Aza + 75 Doc | Phase 1: Level 3 - 100 Aza + 75 Doc | Phase 1: Level 4 - 150 Aza + 75 Doc | Phase 2 - Aza + Doc Initial RPTD | Phase 2 - Aza + Doc Reduced RPTD |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase 1, Starting Dose Level 1: 75 mg/m^2 of Azacitidine (Aza), 60 mg/m^2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Phase 1, Starting Dose Level 2: 75 mg/m^2 of Azacitidine (Aza), 75 mg/m^2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Phase 1, Starting Dose Level 3: 100 mg/m^2 of Azacitidine (Aza), 75 mg/m^2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Phase 1, Starting Dose Level 1: 150 mg/m^2 of Azacitidine (Aza), 75 mg/m^2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel; and Prednisone; with optional growth factor support (pegfilgrastim/filgrastim). | All Phase 2 participants who received at least one reduced dose of the combination of Azacitidine and Docetaxel with 5 mg of Prednisone at the recommended phase two dose level (RPTD). |
| Measure Participants | 3 | 1 | 3 | 6 | 5 | 1 |
| Number [participants] |
0
0%
|
1
14.3%
|
2
9.1%
|
4
NaN
|
3
NaN
|
0
NaN
|
| Title | Number of Participants Achieving Complete Response (CR) or Partial Response (CR) to Protocol Therapy. |
|---|---|
| Description | Number of participants achieving Complete Response (CR) or Partial Response to protocol therapy according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 Criteria. Per RECIST 1.0 for target lesions and assessed by MRI: "Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; " |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of evaluable participants with measurable disease on CT scan. Only 10 of the 19 evaluable participants had measurable disease on CT Scan. |
| Arm/Group Title | Phase 1: Level 1 - 75 Aza + 60 Doc | Phase 1: Level 2 - 75 Aza + 75 Doc | Phase 1: Level 3 - 100 Aza + 75 Doc | Phase 1: Level 4 - 150 Aza + 75 Doc | Phase 2 - Aza + Doc Initial RPTD |
|---|---|---|---|---|---|
| Arm/Group Description | Phase 1, Starting Dose Level 1: 75 mg/m2 of Azacitidine (Aza), 60 mg/m2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Phase 1, Starting Dose Level 2: 75 mg/m2 of Azacitidine (Aza), 75 mg/m2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Phase 1, Starting Dose Level 3: 100 mg/m2 of Azacitidine (Aza), 75 mg/m2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Phase 1, Starting Dose Level 4: 150 mg/m2 of Azacitidine (Aza), 75 mg/m2 of Docetaxel (Doc) with dose escalation/de-escalation design, and 5 mg of Prednisone, with growth factor support; GADD45α methylation and expression analysis, with optional growth factor support (pegfilgrastim/filgrastim) | Initial Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel; and Prednisone; with optional growth factor support (pegfilgrastim/filgrastim). |
| Measure Participants | 2 | 0 | 2 | 3 | 3 |
| Complete Response (CR) |
0
0%
|
1
14.3%
|
0
0%
|
0
NaN
|
|
| Partial Response (PR) |
0
0%
|
0
0%
|
1
4.5%
|
1
NaN
|
| Title | Duration of Response |
|---|---|
| Description | Length of time from the date of first observation of complete response (CR) or partial response (PR) to the date of first observation of disease progression, according to prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 1 (PCWG1) criteria. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks. |
| Time Frame | Up to 4.5 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The 10 participants in both Phase 1 and Phase 2 who achieved PSA response. |
| Arm/Group Title | All Study Participants Achieving PSA Response |
|---|---|
| Arm/Group Description | All study participants who achieved PSA response to protocol therapy. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks. |
| Measure Participants | 10 |
| Median (Full Range) [weeks] |
20.5
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | The time from the date of start of treatment until the first documented or confirmed disease progression, or death related to prostate cancer, whichever is earlier. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Study Participants |
|---|---|
| Arm/Group Description | All study participants who received at least one dose of combination Azacitidine + Docetaxel, and 5 mg of Prednisone in either Phase 1 or Phase 2. |
| Measure Participants | 22 |
| Median (95% Confidence Interval) [months] |
4.9
|
| Title | Overall Survival (OS) |
|---|---|
| Description | The time from the date of initiation of study treatment until date of death from any cause. |
| Time Frame | Up to 4.5 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Study Participants |
|---|---|
| Arm/Group Description | All study participants who received at least one dose of combination Azacitidine + Docetaxel, and 5 mg of Prednisone in either Phase 1 or Phase 2. |
| Measure Participants | 22 |
| Median (95% Confidence Interval) [months] |
19.5
|
| Title | Number of Participants Experiencing Adverse Events After Beginning Protocol Therapy. |
|---|---|
| Description | |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All study participants who received at least one dose of combination Azacitidine + Docetaxel, and 5 mg of Prednisone in either Phase 1 or Phase 2. |
| Arm/Group Title | Level 1 - 75 Aza + 60 Doc | Level 2 - 75 Aza + 75 Doc | Level 3 - 100 Aza + 75 Doc | Level 4 - 150 Aza + 75 Doc |
|---|---|---|---|---|
| Arm/Group Description | 75 mg/m2 of Azacitidine (Aza) and 60 mg/m2 of Docetaxel (Doc) | 75 mg/m2 of Azacitidine (Aza) and 75 mg/m2 of Docetaxel (Doc) | 100 mg/m2 of Azacitidine (Aza) and 75 mg/m2 of Docetaxel (Doc) | 150 mg/m2 of Azacitidine (Aza) and 75 mg/m2 of Docetaxel (Doc) |
| Measure Participants | 3 | 4 | 3 | 12 |
| Number [participants] |
3
20%
|
4
57.1%
|
3
13.6%
|
12
NaN
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All Phase 1 and Phase 2 participants | |||||||
| Arm/Group Title | Level 1 - 75 Aza + 60 Doc | Level 2 - 75 Aza + 75 Doc | Level 3 - 100 Aza + 75 Doc | Level 4 - 150 Aza + 75 Doc | ||||
| Arm/Group Description | 75 mg/m2 of Azacitidine (Aza) and 60 mg/m2 of Docetaxel (Doc) | 75 mg/m2 of Azacitidine (Aza) and 75 mg/m2 of Docetaxel (Doc) | 100 mg/m2 of Azacitidine (Aza) and 75 mg/m2 of Docetaxel (Doc) | 150 mg/m2 of Azacitidine (Aza) and 75 mg/m2 of Docetaxel (Doc) | ||||
All Cause Mortality |
||||||||
| Level 1 - 75 Aza + 60 Doc | Level 2 - 75 Aza + 75 Doc | Level 3 - 100 Aza + 75 Doc | Level 4 - 150 Aza + 75 Doc | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Level 1 - 75 Aza + 60 Doc | Level 2 - 75 Aza + 75 Doc | Level 3 - 100 Aza + 75 Doc | Level 4 - 150 Aza + 75 Doc | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 0/4 (0%) | 1/3 (33.3%) | 4/12 (33.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Hemoglobin | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gastrointestinal disorders | ||||||||
| Diarrhea | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||||||
| Chest Pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Fatigue | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||||
| Febrile Neutropenia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 3/12 (25%) | 3 |
| Infection, normal ANC, Catheter-related | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Hyperkalemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hyponatremia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 3 |
| Nervous system disorders | ||||||||
| CNS cerebrovascular ischemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Renal and urinary disorders | ||||||||
| Renal | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| Level 1 - 75 Aza + 60 Doc | Level 2 - 75 Aza + 75 Doc | Level 3 - 100 Aza + 75 Doc | Level 4 - 150 Aza + 75 Doc | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 4/4 (100%) | 3/3 (100%) | 12/12 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Hemoglobin | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 5/12 (41.7%) | 62 |
| Lymphopenia | 2/3 (66.7%) | 2 | 3/4 (75%) | 10 | 2/3 (66.7%) | 9 | 4/12 (33.3%) | 51 |
| Leukocytes | 1/3 (33.3%) | 3 | 2/4 (50%) | 19 | 3/3 (100%) | 12 | 8/12 (66.7%) | 72 |
| Neutrophils | 3/3 (100%) | 5 | 2/4 (50%) | 10 | 3/3 (100%) | 7 | 6/12 (50%) | 31 |
| Platelets | 1/3 (33.3%) | 3 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 13 |
| Edema limbs | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 |
| Edema: head and neck | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Edema: trunk/genital | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Hemolysis | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Cardiac disorders | ||||||||
| Cardiac Arrhythmia - Other | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypertension | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypotension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 |
| Ventricular tachycardia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Eye disorders | ||||||||
| Blurred vision | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Watering Eyes | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gastrointestinal disorders | ||||||||
| Diarrhea | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 3/12 (25%) | 4 |
| Nausea | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 2 |
| Vomiting | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 3 |
| Abdominal Distension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Constipation | 2/3 (66.7%) | 3 | 3/4 (75%) | 5 | 2/3 (66.7%) | 2 | 7/12 (58.3%) | 9 |
| Dehydration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dry Mouth | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Esophagitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Heartburn | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hemorrhoids | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Mucositis Oral | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 |
| Periodontal Disease | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Taste Alteration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||||||
| Pain | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 4/12 (33.3%) | 9 |
| Fatigue | 2/3 (66.7%) | 3 | 1/4 (25%) | 3 | 3/3 (100%) | 3 | 8/12 (66.7%) | 9 |
| Back Pain | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 4/12 (33.3%) | 7 |
| Weight loss | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 0/12 (0%) | 0 |
| Fever | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 2/12 (16.7%) | 2 |
| Chest Pain | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Insomnia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Joint Pain | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 |
| Oral hemorrhage | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 |
| Oral pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pain in extremity | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 |
| Rigors/Chills | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Sweating | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Immune system disorders | ||||||||
| Allergy - Other | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||||
| Upper respiratory infection | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 1/12 (8.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Allergic reaction | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 0/3 (0%) | 0 | 3/12 (25%) | 4 |
| Injection Site Reaction | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hypoalbuminemia | 2/3 (66.7%) | 2 | 2/4 (50%) | 4 | 2/3 (66.7%) | 4 | 3/12 (25%) | 18 |
| Anorexia | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 2/3 (66.7%) | 2 | 3/12 (25%) | 4 |
| Hypocalcemia | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 1/3 (33.3%) | 3 | 2/12 (16.7%) | 2 |
| Hyperkalemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 4/12 (33.3%) | 10 |
| Alkaline phosphatase increased | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 3 |
| Hyponatremia | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 11 |
| Hypernatremia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 4 |
| Creatinine increased | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 |
| Hypokalemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 2/12 (16.7%) | 2 |
| Acidosis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Alanine aminotransferase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Aspartate aminotransferase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hyperbilirubinemia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hyperglycemia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypermagnesemia | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Hypoglycemia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscle Weakness | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 |
| Musculosketal - Other | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 |
| Osteonecrosis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Nervous system disorders | ||||||||
| Peripheral sensory neuropathy | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 4/12 (33.3%) | 6 |
| Dizziness | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Anxiety | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Syncope | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Renal - Other | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Urinary retention | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 0/3 (0%) | 0 | 1/4 (25%) | 4 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 4/12 (33.3%) | 4 |
| Rash | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 2/12 (16.7%) | 4 |
| Dry Skin | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
| Nail Changes | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Rakesh Singal MD |
|---|---|
| Organization | University of Miami |
| Phone | 305-243-9544 |
| rsingal@med.miami.edu |
- 20061143
- SCCC-2006080
- WIRB-20070344
- 20140376