A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer
Study Details
Study Description
Brief Summary
This study will look at the effect of adding the drug Palbociclib to CAD (Combined Androgen Deprivation) therapy in patients with RB (Retinoblastoma Protein) positive hormone sensitive prostate cancer.
The investigators hypothesize that the addition of Palbociclib to initial ADT (Androgen Deprivation Therapy) in patients with newly metastatic RB-positive prostate cancer may significantly increase the efficacy of ADT.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Patients will undergo exams, tests, and procedures to determine if they are eligible to participate. Subjects will be randomized to one of two groups. Patients randomized to Arm 1 - Patients will receive the LHRH agonist every 3 months. Patients will also take 50 mg. of bicalutamide by mouth every day. Bicalutamide comes in tablet form. This arm is broken down into periods of time called cycles, starting with cycle 1 then cycle 2, and so on.Each cycle is 28 days long. If randomized to Arm 2 - Patients will receive the LHRH agonist every 3 months. Patients will also take 50 mg. of bicalutamide by mouth every day. Patients will also take 125 mg. of Ibrance® daily for 21 days, and then will stop taking Ibrance® for 7 days. Patients will then begin taking Ibrance® again after 7 days off. Patients will keep repeating this cycle every 28 days. When the patient starts the first 28 day cycle that will be cycle 1, then cycle 2, and so on. During each cycle the patient will come in for routine and research tests and procedures for patient safety, to see how patients are doing, and for research purposes. The researchers will ask patients to complete a drug diary to track bicalutamide and Ibrance® administration. The total time of study participation depends on how a patient responds to the study medications. Patients may be on the study for a short period of time, such as a week, or for a longer period of time, such as a few years. Patients may continue on study treatment until one of the following: cancer progresses (gets worse); another illness or condition develops that prevents study participation; unacceptable side effects occur; drug is delayed more than 4 weeks; patient withdraws consent; the study doctor thinks the patient should stop; the patient does not follow researcher's instructions; the study is cancelled.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: ADT Alone Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
Drug: Bicalutamide
Other Names:
Drug: Zoladex
Other Names:
Drug: Lupron Depot
Other Names:
|
| Experimental: ADT + Ibrance® Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
Drug: Ibrance
Other Names:
Drug: Bicalutamide
Other Names:
Drug: Zoladex
Other Names:
Drug: Lupron Depot
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm [28 weeks]
The primary analysis will be assessment of the proportion of patients who achieve a (Prostate-specific antigen) PSA < 4ng/mL after seven months of protocol treatment in each arm.
Secondary Outcome Measures
- Number of Participants With Grade >=3 Adverse Events That Are Possibly, Probably or Definitely Related to Study Treatment [Up to 54 months]
Grade >=3 adverse events that are possibly, probably or definitely related to study treatment, reported by number of participants affected in each arm
- Duration of Therapy [Up to 54 months]
Duration of therapy will be reported to describe tolerability within each arm.
- Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL) [Up to 54 months]
- Biochemical Progression-free Survival Rate [Up to 54 months]
12-month biochemical progression-free survival rate will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first. Described by arm using Kaplan-Meier methods.
- Clinical Progression-free Survival Rate [Up to 54 months]
12-month clinical progression-free survival rate will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first. Described by arm using Kaplan-Meier methods.
- Frequency of Dose Modification [Up to 54 months]
Dose modifications will be reported to describe tolerability for arm 2 only (Ibrance®)
- Frequency of Treatment Delay [Up to 54 months]
Treatment delays will be reported to describe tolerability within each arm.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have pathologic diagnosis of prostate cancer.
-
Have hormone-sensitive metastatic disease (M1) as evidenced by soft tissue and/or bony metastases.
-
Patients may either be untreated for their newly diagnosed metastatic disease (preferred as much as possible) or have started androgen deprivation therapy. Patients who have started androgen deprivation therapy for the treatment of their newly diagnosed metastatic disease are eligible as long as the duration of treatment is less than or equal to 2 weeks (14days) prior to registration. The start date of androgen deprivation is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not the date when an oral antiandrogen started.
-
Patients must have a minimum PSA (Prostate-Specific Antigen) ≥ 5 ng/mL within 60 days of registration or prior to the initiation of androgen deprivation for patients who have started androgen deprivation therapy.
-
Agree to undergo a biopsy of at least one metastatic site for RB (Retinoblastoma Protein) status evaluation. Adequate metastatic tissue from prior biopsy/resection can be used if available in lieu of a biopsy.
-
ECOG performance status of 0-2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death).
-
Patients may have received prior neoadjuvant and/or adjuvant hormonal therapy, for non-metastatic disease but it must not have lasted for more than 36 months. At least 12 months must have elapsed since completion of androgen deprivation therapy in the neoadjuvant and/or adjuvant setting.
-
Within 14 days prior to registration patients must have adequate organ and marrow function: White Blood Cell (WBC) count ≥ 3,000/μl, Absolute Neutrophil Count (ANC) ≥ 1,500/μl, Platelet Count ≥ 100,000/μl, Serum Creatinine ≥1.5 x the institutional upper limits of normal or corrected creatinine clearance of ≥ 50 mg/ml/hr/1.73 m2 BSA (Body Surface Area), Bilirubin within the institutional limits of normal, AST (Aspartate Aminotransferase) ≤ 2 x upper limits of normal, ALT (Alanine Aminotransferase) ≤ 2 x upper limits of normal.
-
Patients must be able to take oral medication without crushing, dissolving or chewing tablets.
-
Patients may have received prior radiation therapy or surgery. However, at least 14 days must have elapsed since completion of radiation therapy or surgery and patient must have only grade 2 or less adverse effects at the time of registration.
-
Patients must agree to use highly effective contraception during treatment and for a period of 90 days after ending treatment with PD 0332991.
-
Ability to understand and the willingness to sign a written informed consent document that is approved by an institutional review board.
Exclusion Criteria:
-
Patients who have received androgen deprivation therapy for greater than 14 days (LHRH-agonist or antagonist) for the treatment of their newly diagnosed metastatic disease prior to enrollment are not eligible for this study.
-
Patients who are currently being treated with strong CYP3A4 inhibitors (e.g., amprenavir, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit) or strong inducers (e.g., carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine and St. John's wort) must either discontinue these drugs or are ineligible.
-
Patients must refrain from the use of proton pump inhibitors. If needed, alternative antacid therapies may be used including H2-receptor antagonists, and locally acting antacids.
-
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
-
Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year.
-
HIV-positive patients on combination antiretroviral therapy are ineligible .
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Cancer Center | Duarte | California | United States | 91010 |
| 2 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 3 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | United States | 21231 |
| 4 | University of Michigan Hospital | Ann Arbor | Michigan | United States | 48109 |
| 5 | Washington University in St. Louis | Saint Louis | Missouri | United States | 63110 |
| 6 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
| 7 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 8 | Huntsman Cancer Institute, University of Utah | Salt Lake City | Utah | United States | 84112 |
Sponsors and Collaborators
- University of Michigan Rogel Cancer Center
- University of Utah
- Vanderbilt-Ingram Cancer Center
- Johns Hopkins University
- Thomas Jefferson University
- Washington University School of Medicine
- Northwestern University
- City of Hope Comprehensive Cancer Center
Investigators
- Principal Investigator: Maha Hussain, MD, FACP, FASCO, University of Michigan Comprehensive Cancer Center and Northwestern University
Study Documents (Full-Text)
More Information
Publications
None provided.- UMCC 2013.117
- HUM00082715
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 72 patients were enrolled to the trial. Seven patients did not have adequate tissue for testing retinoblastoma status. Two patients tested negative for retinoblastoma and one patient was found to have small cell metastasis and not adenocarcinoma. 62 patients were randomized. |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Period Title: Overall Study | ||
| STARTED | 20 | 42 |
| Initiated Treatment | 20 | 40 |
| COMPLETED | 20 | 40 |
| NOT COMPLETED | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | ADT Alone | ADT + Ibrance® | Total |
|---|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Total of all reporting groups |
| Overall Participants | 20 | 42 | 62 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
67.5
|
67.5
|
67.5
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
20
100%
|
42
100%
|
62
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
3
15%
|
2
4.8%
|
5
8.1%
|
| Not Hispanic or Latino |
16
80%
|
39
92.9%
|
55
88.7%
|
| Unknown or Not Reported |
1
5%
|
1
2.4%
|
2
3.2%
|
Outcome Measures
| Title | Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm |
|---|---|
| Description | The primary analysis will be assessment of the proportion of patients who achieve a (Prostate-specific antigen) PSA < 4ng/mL after seven months of protocol treatment in each arm. |
| Time Frame | 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 72 patients were enrolled to the trial. Seven patients did not have adequate tissue for testing retinoblastoma status. Two patients tested negative for retinoblastoma and one patient was found to have small cell metastasis and not adenocarcinoma. 62 patients were randomized. 60 randomized patients initiated therapy on trial. |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 20 | 40 |
| Count of Participants [Participants] |
16
80%
|
32
76.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ADT Alone, ADT + Ibrance® |
|---|---|---|
| Comments | With 20 patients treated with ADT and 40 treated with ADT + palbociclib there is a 64.2% power to detect a 20% difference in proportions with a one-sided type I error of 0.10 using the mid p-value method of the Fisher's exact test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.87 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | Mid P-value | |
| Title | Number of Participants With Grade >=3 Adverse Events That Are Possibly, Probably or Definitely Related to Study Treatment |
|---|---|
| Description | Grade >=3 adverse events that are possibly, probably or definitely related to study treatment, reported by number of participants affected in each arm |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 20 | 40 |
| Number [participants] |
0
0%
|
23
54.8%
|
| Title | Duration of Therapy |
|---|---|
| Description | Duration of therapy will be reported to describe tolerability within each arm. |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 20 | 40 |
| Mean (Standard Deviation) [months] |
22.4
(13.1)
|
22.0
(13.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ADT Alone, ADT + Ibrance® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.92 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL) |
|---|---|
| Description | |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). Bicalutamide Zoladex Lupron Depot | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). Ibrance Bicalutamide Zoladex Lupron Depot |
| Measure Participants | 20 | 40 |
| Count of Participants [Participants] |
13
65%
|
22
52.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ADT Alone, ADT + Ibrance® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.50 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | Mid p-value | |
| Title | Biochemical Progression-free Survival Rate |
|---|---|
| Description | 12-month biochemical progression-free survival rate will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first. Described by arm using Kaplan-Meier methods. |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 20 | 40 |
| 12-month |
74.7
373.5%
|
76.5
182.1%
|
| 26-month (time of last event in Arm 1) |
45.8
229%
|
59.4
141.4%
|
| 43-month (time of last event in Arm 2) |
45.8
229%
|
33.9
80.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ADT Alone, ADT + Ibrance® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.72 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Clinical Progression-free Survival Rate |
|---|---|
| Description | 12-month clinical progression-free survival rate will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first. Described by arm using Kaplan-Meier methods. |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 20 | 40 |
| 12-month |
77.7
388.5%
|
83.8
199.5%
|
| 22-month (time of last event in Arm 1) |
64.8
324%
|
77.7
185%
|
| 32-month (time of last event in Arm 2) |
64.8
324%
|
58.5
139.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ADT Alone, ADT + Ibrance® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.76 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Frequency of Dose Modification |
|---|---|
| Description | Dose modifications will be reported to describe tolerability for arm 2 only (Ibrance®) |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT + Ibrance® |
|---|---|
| Arm/Group Description | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 40 |
| No Dose Reduction (Palbociclib 125mg/day) |
28
140%
|
| 1 Dose Reduction, to Palbociclib 100mg/day |
5
25%
|
| 2 Dose Reductions, to Palbociclib 75mg/day |
7
35%
|
| Title | Frequency of Treatment Delay |
|---|---|
| Description | Treatment delays will be reported to describe tolerability within each arm. |
| Time Frame | Up to 54 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ADT Alone | ADT + Ibrance® |
|---|---|---|
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). |
| Measure Participants | 20 | 40 |
| No Treatment delay of Bicalutamide |
19
95%
|
35
83.3%
|
| Treatment Delay of Bicalutamide |
1
5%
|
5
11.9%
|
| No Treatment Delay of Palbociclib |
0
0%
|
21
50%
|
| Treatment Delay of Palbociclib |
0
0%
|
19
45.2%
|
Adverse Events
| Time Frame | Adverse events (AEs) were collected up to 44 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | ADT Alone | ADT + Ibrance® | ||
| Arm/Group Description | Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection). | ||
All Cause Mortality |
||||
| ADT Alone | ADT + Ibrance® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/20 (0%) | 1/40 (2.5%) | ||
Serious Adverse Events |
||||
| ADT Alone | ADT + Ibrance® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/20 (25%) | 7/40 (17.5%) | ||
| Cardiac disorders | ||||
| Aortic valve disease | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Pancreatitis | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Small intestinal obstruction | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Vomiting | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| General disorders | ||||
| Fever | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| General disorders and administration site conditions - Other, specify | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Infections and infestations | ||||
| Sepsis | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Urinary tract infection | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Nervous system disorders | ||||
| Syncope | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Urinary retention | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Hypoxia | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Vascular disorders | ||||
| Hematoma | 0/20 (0%) | 0 | 1/40 (2.5%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| ADT Alone | ADT + Ibrance® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 40/40 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 4/20 (20%) | 5 | 13/40 (32.5%) | 23 |
| Blood and lymphatic system disorders - Other | 1/20 (5%) | 1 | 3/40 (7.5%) | 5 |
| Bone marrow hypocellular | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Lymph node pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Cardiac disorders | ||||
| Aortic valve disease | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Cardiac disorders - Other | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| Chest pain - cardiac | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Left ventricular systolic dysfunction | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Sinus bradycardia | 2/20 (10%) | 2 | 2/40 (5%) | 2 |
| Ear and labyrinth disorders | ||||
| Ear and labyrinth disorders - Other | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Hearing impaired | 1/20 (5%) | 1 | 4/40 (10%) | 4 |
| Tinnitus | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Vertigo | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Vestibular disorder | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Eye disorders | ||||
| Blurred vision | 0/20 (0%) | 0 | 3/40 (7.5%) | 3 |
| Dry eye | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| Eye disorders - Other | 1/20 (5%) | 1 | 3/40 (7.5%) | 4 |
| Eye pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Glaucoma | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/20 (10%) | 3 | 6/40 (15%) | 6 |
| Bloating | 2/20 (10%) | 2 | 0/40 (0%) | 0 |
| Constipation | 2/20 (10%) | 2 | 14/40 (35%) | 18 |
| Dental caries | 1/20 (5%) | 1 | 5/40 (12.5%) | 5 |
| Diarrhea | 2/20 (10%) | 2 | 10/40 (25%) | 12 |
| Dry mouth | 2/20 (10%) | 2 | 3/40 (7.5%) | 3 |
| Dyspepsia | 1/20 (5%) | 3 | 1/40 (2.5%) | 1 |
| Dysphagia | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Fecal incontinence | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Flatulence | 0/20 (0%) | 0 | 3/40 (7.5%) | 3 |
| Gastroesophageal reflux disease | 0/20 (0%) | 0 | 4/40 (10%) | 4 |
| Gastrointestinal disorders - Other | 2/20 (10%) | 2 | 8/40 (20%) | 8 |
| Gastrointestinal pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Hemorrhoidal hemorrhage | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Hemorrhoids | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Mucositis oral | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Nausea | 4/20 (20%) | 6 | 9/40 (22.5%) | 13 |
| Oral pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Rectal hemorrhage | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Stomach pain | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Toothache | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Vomiting | 2/20 (10%) | 3 | 5/40 (12.5%) | 17 |
| General disorders | ||||
| Chills | 0/20 (0%) | 0 | 5/40 (12.5%) | 5 |
| Edema limbs | 7/20 (35%) | 8 | 9/40 (22.5%) | 11 |
| Fatigue | 12/20 (60%) | 16 | 23/40 (57.5%) | 29 |
| Fever | 1/20 (5%) | 2 | 0/40 (0%) | 0 |
| Flu like symptoms | 3/20 (15%) | 6 | 6/40 (15%) | 10 |
| Gait disturbance | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| General disorders and administration site conditions - Other | 2/20 (10%) | 3 | 8/40 (20%) | 10 |
| Injection site reaction | 0/20 (0%) | 0 | 3/40 (7.5%) | 3 |
| Irritability | 2/20 (10%) | 2 | 1/40 (2.5%) | 1 |
| Non-cardiac chest pain | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Pain | 4/20 (20%) | 7 | 12/40 (30%) | 17 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Immune system disorders | ||||
| Allergic reaction | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Infections and infestations | ||||
| Infections and infestations - Other | 2/20 (10%) | 2 | 0/40 (0%) | 0 |
| Lip infection | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Nail infection | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Otitis externa | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Papulopustular rash | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Pharyngitis | 2/20 (10%) | 2 | 1/40 (2.5%) | 1 |
| Scrotal infection | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Sinusitis | 2/20 (10%) | 5 | 1/40 (2.5%) | 1 |
| Skin infection | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Tooth infection | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Upper respiratory infection | 2/20 (10%) | 2 | 9/40 (22.5%) | 14 |
| Urinary tract infection | 1/20 (5%) | 1 | 4/40 (10%) | 5 |
| Injury, poisoning and procedural complications | ||||
| Aortic injury | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Bruising | 0/20 (0%) | 0 | 5/40 (12.5%) | 5 |
| Burn | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Fall | 1/20 (5%) | 1 | 3/40 (7.5%) | 3 |
| Fracture | 1/20 (5%) | 2 | 2/40 (5%) | 2 |
| Injury, poisoning and procedural complications - Other | 2/20 (10%) | 2 | 1/40 (2.5%) | 1 |
| Seroma | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Spinal fracture | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 4/20 (20%) | 5 | 5/40 (12.5%) | 7 |
| Alkaline phosphatase increased | 1/20 (5%) | 2 | 4/40 (10%) | 4 |
| Aspartate aminotransferase increased | 3/20 (15%) | 4 | 6/40 (15%) | 9 |
| Blood bilirubin increased | 1/20 (5%) | 1 | 1/40 (2.5%) | 2 |
| Cholesterol high | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Creatinine increased | 3/20 (15%) | 5 | 3/40 (7.5%) | 6 |
| Electrocardiogram QT corrected interval prolonged | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Investigations - Other | 2/20 (10%) | 2 | 3/40 (7.5%) | 4 |
| Lipase increased | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Lymphocyte count decreased | 1/20 (5%) | 1 | 6/40 (15%) | 12 |
| Neutrophil count decreased | 0/20 (0%) | 0 | 25/40 (62.5%) | 96 |
| Platelet count decreased | 0/20 (0%) | 0 | 14/40 (35%) | 29 |
| Weight gain | 6/20 (30%) | 12 | 7/40 (17.5%) | 10 |
| Weight loss | 2/20 (10%) | 2 | 3/40 (7.5%) | 6 |
| White blood cell decreased | 1/20 (5%) | 1 | 19/40 (47.5%) | 65 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 0/20 (0%) | 0 | 1/40 (2.5%) | 2 |
| Dehydration | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| Hypercalcemia | 4/20 (20%) | 4 | 3/40 (7.5%) | 3 |
| Hyperglycemia | 4/20 (20%) | 13 | 15/40 (37.5%) | 36 |
| Hyperkalemia | 2/20 (10%) | 3 | 4/40 (10%) | 4 |
| Hypermagnesemia | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Hypernatremia | 1/20 (5%) | 2 | 1/40 (2.5%) | 4 |
| Hypertriglyceridemia | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Hypoalbuminemia | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Hypoglycemia | 1/20 (5%) | 3 | 0/40 (0%) | 0 |
| Hypomagnesemia | 1/20 (5%) | 1 | 3/40 (7.5%) | 3 |
| Hyponatremia | 1/20 (5%) | 2 | 1/40 (2.5%) | 2 |
| Hypophosphatemia | 4/20 (20%) | 5 | 7/40 (17.5%) | 11 |
| Metabolism and nutrition disorders - Other | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 6/20 (30%) | 8 | 5/40 (12.5%) | 9 |
| Arthritis | 3/20 (15%) | 4 | 4/40 (10%) | 6 |
| Back pain | 5/20 (25%) | 9 | 9/40 (22.5%) | 14 |
| Bone pain | 1/20 (5%) | 1 | 7/40 (17.5%) | 8 |
| Buttock pain | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Flank pain | 0/20 (0%) | 0 | 3/40 (7.5%) | 3 |
| Generalized muscle weakness | 1/20 (5%) | 1 | 5/40 (12.5%) | 7 |
| Joint range of motion decreased | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Muscle weakness lower limb | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Muscle weakness upper limb | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Musculoskeletal and connective tissue disorder - Other | 3/20 (15%) | 6 | 8/40 (20%) | 10 |
| Myalgia | 1/20 (5%) | 1 | 8/40 (20%) | 12 |
| Neck pain | 1/20 (5%) | 3 | 3/40 (7.5%) | 3 |
| Osteonecrosis of jaw | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Osteoporosis | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| Pain in extremity | 7/20 (35%) | 7 | 4/40 (10%) | 4 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other | 1/20 (5%) | 2 | 1/40 (2.5%) | 1 |
| Nervous system disorders | ||||
| Akathisia | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Amnesia | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Cognitive disturbance | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Concentration impairment | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Dizziness | 4/20 (20%) | 5 | 9/40 (22.5%) | 13 |
| Dysgeusia | 0/20 (0%) | 0 | 3/40 (7.5%) | 5 |
| Headache | 2/20 (10%) | 2 | 6/40 (15%) | 8 |
| Lethargy | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Memory impairment | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Nervous system disorders - Other | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| Paresthesia | 3/20 (15%) | 5 | 3/40 (7.5%) | 4 |
| Peripheral motor neuropathy | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Peripheral sensory neuropathy | 1/20 (5%) | 1 | 6/40 (15%) | 7 |
| Presyncope | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Radiculitis | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Somnolence | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Syncope | 2/20 (10%) | 3 | 0/40 (0%) | 0 |
| Tremor | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Psychiatric disorders | ||||
| Anxiety | 3/20 (15%) | 3 | 3/40 (7.5%) | 4 |
| Depression | 3/20 (15%) | 3 | 8/40 (20%) | 10 |
| Insomnia | 4/20 (20%) | 4 | 9/40 (22.5%) | 9 |
| Libido decreased | 2/20 (10%) | 2 | 0/40 (0%) | 0 |
| Psychiatric disorders - Other | 3/20 (15%) | 4 | 2/40 (5%) | 2 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Chronic kidney disease | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Cystitis noninfective | 2/20 (10%) | 2 | 2/40 (5%) | 2 |
| Hematuria | 3/20 (15%) | 3 | 3/40 (7.5%) | 4 |
| Proteinuria | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Renal and urinary disorders - Other | 1/20 (5%) | 1 | 2/40 (5%) | 2 |
| Renal calculi | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Urinary frequency | 3/20 (15%) | 3 | 7/40 (17.5%) | 7 |
| Urinary incontinence | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Urinary retention | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Urinary tract obstruction | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Urinary tract pain | 2/20 (10%) | 2 | 2/40 (5%) | 2 |
| Urinary urgency | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Reproductive system and breast disorders | ||||
| Breast pain | 1/20 (5%) | 2 | 1/40 (2.5%) | 1 |
| Erectile dysfunction | 2/20 (10%) | 2 | 3/40 (7.5%) | 3 |
| Gynecomastia | 4/20 (20%) | 4 | 8/40 (20%) | 8 |
| Pelvic pain | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Reproductive system and breast disorders - Other | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Testicular pain | 1/20 (5%) | 1 | 3/40 (7.5%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic rhinitis | 2/20 (10%) | 5 | 6/40 (15%) | 6 |
| Atelectasis | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Cough | 4/20 (20%) | 5 | 16/40 (40%) | 19 |
| Dyspnea | 2/20 (10%) | 2 | 9/40 (22.5%) | 9 |
| Epistaxis | 0/20 (0%) | 0 | 4/40 (10%) | 5 |
| Hoarseness | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Laryngeal inflammation | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Nasal congestion | 1/20 (5%) | 1 | 6/40 (15%) | 6 |
| Postnasal drip | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Productive cough | 0/20 (0%) | 0 | 3/40 (7.5%) | 7 |
| Respiratory, thoracic and mediastinal disorders - Other | 1/20 (5%) | 1 | 3/40 (7.5%) | 4 |
| Sinus disorder | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Sleep apnea | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Sneezing | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Sore throat | 2/20 (10%) | 3 | 5/40 (12.5%) | 7 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 4/20 (20%) | 4 | 10/40 (25%) | 10 |
| Dry skin | 1/20 (5%) | 1 | 5/40 (12.5%) | 5 |
| Nail loss | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Palmar-plantar erythrodysesthesia syndrome | 0/20 (0%) | 0 | 2/40 (5%) | 3 |
| Photosensitivity | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Pruritus | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
| Rash acneiform | 0/20 (0%) | 0 | 2/40 (5%) | 5 |
| Rash maculo-papular | 1/20 (5%) | 1 | 2/40 (5%) | 3 |
| Scalp pain | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Skin and subcutaneous tissue disorders - Other | 4/20 (20%) | 6 | 10/40 (25%) | 13 |
| Skin atrophy | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Surgical and medical procedures | ||||
| Surgical and medical procedures - Other | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Vascular disorders | ||||
| Flushing | 0/20 (0%) | 0 | 1/40 (2.5%) | 1 |
| Hot flashes | 16/20 (80%) | 19 | 31/40 (77.5%) | 36 |
| Hypertension | 2/20 (10%) | 2 | 8/40 (20%) | 17 |
| Hypotension | 1/20 (5%) | 1 | 0/40 (0%) | 0 |
| Thromboembolic event | 0/20 (0%) | 0 | 2/40 (5%) | 2 |
| Vascular disorders - Other | 1/20 (5%) | 1 | 1/40 (2.5%) | 1 |
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 | Phillip Palmbos, M.D., Ph.D. |
|---|---|
| Organization | University of Michigan Rogel Cancer Center |
| Phone | 734-936-3591 |
| ppalmbos@umich.edu |
- UMCC 2013.117
- HUM00082715