A Study to Assess the Safety of Continued Administration of MDV3100 in Subjects With Prostate Cancer Who Showed Benefit From Prior Exposure to MDV3100
Study Details
Study Description
Brief Summary
A study to assess the safety of continued administration of MDV3100 in subjects with Prostate Cancer who have already undergone treatment with MDV3100 and showed benefit.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This was a multi-center extension study in participants with prostate cancer who have completed MDV3100 treatment study to assess the long-term safety of continued administration of MDV3100, when judged by the investigator to be in the best interest of the participant. For the study duration, all participants with castration-resistant prostate cancer (CRPC) maintained androgen deprivation with a Luteinizing Hormone Releasing Hormone (LHRH) agonist/antagonist unless they underwent bilateral orchiectomy. Participants were discontinued from study drug when the continued administration of study drug was deemed to be not in the participants' best interest by the investigator based on clinical assessment. Throughout the study, safety and tolerability were assessed by the recording of adverse events, monitoring of vital signs and physical examinations, safety laboratory evaluations, and 12-lead electrocardiograms (ECGs). Participants had a safety follow-up visit 30 days after their last dose of study drug. Participants that did not meet any of the discontinuation criteria were eligible to continue to receive treatment with enzalutamide in study 9785-CL-0123 [NCT02960022] upon approval and activation of the study at the participating institution. Participants who enrolled in study 9785-CL-0123 [NCT02960022] were not required to have a safety follow-up visit.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Enzalutamide Participants received 160 mg enzalutamide orally once a day. Participants continued on treatment unless the dose was reduced or treatment was interrupted during the study. |
Drug: Enzalutamide
Oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs) [From the date of the first dose of study drug to 30 days after last dose of study drug; the median duration of treatment was 392 days, and the maximum was 1926 days]
An AE was defined as any untoward medical occurrence in a participant administered study drug or who underwent study procedures and did not necessarily have a causal relationship with treatment. An abnormality identified during a medical test was defined as an AE only if the abnormality induced clinical signs or symptoms, required active intervention, required interruption, or discontinuation of study medication, or was clinically significant in the opinion of the investigator. An AE was defined as serious if it resulted in any of the following outcomes: Death, Was life-threatening, Persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, Congenital anomaly, or birth defect, Inpatient hospitalization or prolongation of hospitalization, Other medically important event. Drug-related AEs were those assessed by the investigator as AEs whose relationship to the to the study drugs could not be ruled out.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has completed a prior study with MDV3100, can be enrolled in this extension study without any interruption in study drug
-
No new clinically significant abnormalities based upon physical examination, safety laboratory data, vital signs, ECG, and other clinical assessments noted from the last visit conducted during the subject's active MDV3100 study prior to initiation of this study
-
Male subjects and their female spouses/partners who are of childbearing potential must be using highly effective contraception1 consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 3 months after final study drug administration. Male subjects must not donate sperm starting at Screening and throughout the study period and for at least 3 months after final study drug administration. 1Highly effective contraception is defined as:
-
Established use of oral, injected or implanted hormonal methods of contraception.
-
Placement of an intrauterine device (IUD) or intrauterine system (IUS).
-
Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal form/gel/film/ cream/suppository
-
Subject agrees not to participate in another interventional study while on treatment
Exclusion Criteria:
Subject will be excluded from participation if any of the following apply:
-
Subject has a history of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumours, brain metastases, or alcoholism.
-
Subject has a history of loss of consciousness or transient ischemic attack within 12 months prior to Day 1 of the completed preceding study.
-
Use of the following prohibited medication/therapies:
-
Concomitant medication that likely could cause clinically relevant drug-to-drug interactions with MDV3100.
-
Other (than MDV3100) androgen-receptor (AR) antagonists (bicalutamide, flutamide, nilutamide).
-
Investigational therapy other than MDV3100 or investigational procedures of any kind.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site US107 | Aurora | Colorado | United States | 80045 |
| 2 | Site US104 | Chicago | Illinois | United States | 60637 |
| 3 | Site US105 | Pittsburgh | Pennsylvania | United States | 15215 |
| 4 | Site US106 | San Antonio | Texas | United States | 78253 |
| 5 | Site MD37301 | Chisinau | Moldova, Republic of | ||
| 6 | Site ZA2701 | George | South Africa | 6529 | |
| 7 | Site ZA2702 | Port Elizabeth | South Africa | 6001 |
Sponsors and Collaborators
- Astellas Pharma Inc
- Medivation, Inc.
Investigators
- Study Chair: Clinical Study Manager, Astellas Pharma Europe B.V.
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 9785-CL-0121
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 1 site in the Republic of Moldova, 2 sites in South Africa and 4 sites in the United States. In order to participate, participants had to complete a prior study with enzalutamide, be in a state of at least stable disease and benefit from continued treatment with enzalutamide in the opinion of the investigator. |
|---|---|
| Pre-assignment Detail | This was an extension study in prostate cancer participants who have received enzalutamide treatment in prior phase 1 studies. The 9785-CL-0121 was an extension of previous enzalutamide studies (9785-CL-0003 [NCT01902251], 9785-CL-0007 [NCT01911728] & 9785-CL-0406 [NCT02225093]). |
| Arm/Group Title | Enzalutamide |
|---|---|
| Arm/Group Description | Participants received 160 mg enzalutamide orally once a day. Participants continued on treatment unless the dose was reduced or treatment was interrupted during the study. |
| Period Title: Overall Study | |
| STARTED | 52 |
| Treatment Received | 52 |
| COMPLETED | 52 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Enzalutamide |
|---|---|
| Arm/Group Description | Participants received 160 mg enzalutamide orally once a day. Participants continued on treatment unless the dose was reduced or treatment was interrupted during the study. |
| Overall Participants | 52 |
| Age (years) [Geometric Mean (Standard Deviation) ] | |
| Geometric Mean (Standard Deviation) [years] |
68.6
(7.39)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
52
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
52
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
3.8%
|
| White |
47
90.4%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
3
5.8%
|
| Duration of Prostate Cancer (months) [Geometric Mean (Standard Deviation) ] | |
| Geometric Mean (Standard Deviation) [months] |
69.4
(64.10)
|
| Primary Gleason Score at Initial Diagnosis (Count of Participants) | |
| Score 3 |
15
28.8%
|
| Score 4 |
13
25%
|
| Score 5 |
4
7.7%
|
| Unknown |
20
38.5%
|
| Secondary Gleason Score at Initial Diagnosis (Count of Participants) | |
| Score 3 |
9
17.3%
|
| Score 4 |
14
26.9%
|
| Score 5 |
9
17.3%
|
| Unknown |
20
38.5%
|
| Total Gleason Score at Initial Diagnosis (Count of Participants) | |
| Score 6 |
5
9.6%
|
| Score 7 |
16
30.8%
|
| Score 8 |
1
1.9%
|
| Score 9 |
13
25%
|
| Unknown |
17
32.7%
|
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) (Count of Participants) | |
| TX - Primary Tumor Cannot be Assessed |
3
5.8%
|
| T0 - No Evidence of Primary Tumor |
1
1.9%
|
| T1 - Clinically Tumor Not Palpable or Visible |
1
1.9%
|
| T2 - Tumor Confined Within the Prostate |
8
15.4%
|
| T3 - Tumor Extends Through the Prostatic Capsule |
13
25%
|
| T4 - Tumor Fixed or Invades Adjacent Structures |
3
5.8%
|
| Unknown |
23
44.2%
|
| Pathologic Tumor Stage (pT) (Count of Participants) | |
| pT2 - Organ Confined |
5
9.6%
|
| pT3 - Extraprostatic Extension |
9
17.3%
|
| pT4 - Invasion of Bladder, Rectum |
1
1.9%
|
| Unknown |
37
71.2%
|
| Regional Lymph Nodes (N) at Initial Diagnosis (Count of Participants) | |
| NX - Regional Lymph Nodes Were Not Assessed |
18
34.6%
|
| N0 - No Regional Lymph Node Metastasis |
15
28.8%
|
| N1 - Metastasis in Regional Lymph Node(s) |
6
11.5%
|
| pNX - Regional Lymph Nodes Not Sampled |
8
15.4%
|
| pN0 - No Positive Regional Nodes |
6
11.5%
|
| pN1 - Metastasis in Regional Nodes(s) |
2
3.8%
|
| Unknown |
36
69.2%
|
| Distant Metastasis at Initial Diagnosis (Count of Participants) | |
| MX - Distant Metastasis Cannot be Assessed |
8
15.4%
|
| M0 - No Distant Metastasis |
12
23.1%
|
| M1 - Distant Metastasis |
9
17.3%
|
| Unknown |
23
44.2%
|
| Treatment Duration in Extension Study (Days) [Number] | |
| <= 60 |
4
|
| > 60 - <182 |
12
|
| >= 182 - <365 |
9
|
| >= 365 |
27
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | An AE was defined as any untoward medical occurrence in a participant administered study drug or who underwent study procedures and did not necessarily have a causal relationship with treatment. An abnormality identified during a medical test was defined as an AE only if the abnormality induced clinical signs or symptoms, required active intervention, required interruption, or discontinuation of study medication, or was clinically significant in the opinion of the investigator. An AE was defined as serious if it resulted in any of the following outcomes: Death, Was life-threatening, Persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, Congenital anomaly, or birth defect, Inpatient hospitalization or prolongation of hospitalization, Other medically important event. Drug-related AEs were those assessed by the investigator as AEs whose relationship to the to the study drugs could not be ruled out. |
| Time Frame | From the date of the first dose of study drug to 30 days after last dose of study drug; the median duration of treatment was 392 days, and the maximum was 1926 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the SAF. |
| Arm/Group Title | Enzalutamide |
|---|---|
| Arm/Group Description | Participants received 160 mg enzalutamide orally once a day. Participants continued on treatment unless the dose was reduced or treatment was interrupted during the study. |
| Measure Participants | 52 |
| Any TEAE |
43
82.7%
|
| Drug-Related TEAEs |
27
51.9%
|
| Deaths |
5
9.6%
|
| Serious TEAEs |
17
32.7%
|
| Drug-Related Serious TEAEs |
5
9.6%
|
| TEAEs Leading to Study Drug Discontinuation |
12
23.1%
|
| Drug-Related TEAEs Lead to Study Discontinuation |
5
9.6%
|
Adverse Events
| Time Frame | From the date of the first dose of study drug to 30 days after last dose of study drug; the median duration of treatment was 392 days, and the maximum was 1926 days | |
|---|---|---|
| Adverse Event Reporting Description | The total number of deaths (all causes) includes deaths reported after the time frame above. | |
| Arm/Group Title | Enzalutimide | |
| Arm/Group Description | Participants received 160 mg enzalutamide orally once a day. Participants continued on treatment unless the dose was reduced or treatment was interrupted during the study. | |
All Cause Mortality |
||
| Enzalutimide | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/52 (3.8%) | |
Serious Adverse Events |
||
| Enzalutimide | ||
| Affected / at Risk (%) | # Events | |
| Total | 17/52 (32.7%) | |
| Cardiac disorders | ||
| Acute myocardial infarction | 1/52 (1.9%) | 1 |
| Atrial fibrillation | 1/52 (1.9%) | 1 |
| Tachycardia | 1/52 (1.9%) | 1 |
| Gastrointestinal disorders | ||
| Anal fissure | 1/52 (1.9%) | 1 |
| Diarrhoea | 1/52 (1.9%) | 1 |
| Pancreatitis acute | 1/52 (1.9%) | 1 |
| Proctalgia | 1/52 (1.9%) | 1 |
| Rectal haemorrhage | 1/52 (1.9%) | 1 |
| General disorders | ||
| Asthenia | 2/52 (3.8%) | 2 |
| Infections and infestations | ||
| Pneumonia | 1/52 (1.9%) | 1 |
| Injury, poisoning and procedural complications | ||
| Femur fracture | 1/52 (1.9%) | 1 |
| Hip fracture | 1/52 (1.9%) | 1 |
| Metabolism and nutrition disorders | ||
| Hypercalcaemia | 1/52 (1.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 1/52 (1.9%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Malignant neoplasm progression | 4/52 (7.7%) | 4 |
| Pancreatic carcinoma | 1/52 (1.9%) | 1 |
| Tonsil cancer | 1/52 (1.9%) | 1 |
| Nervous system disorders | ||
| Cerebrovascular accident | 1/52 (1.9%) | 1 |
| Dysarthria | 1/52 (1.9%) | 1 |
| Hemiparesis | 1/52 (1.9%) | 1 |
| Spinal cord compression | 2/52 (3.8%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pulmonary embolism | 1/52 (1.9%) | 1 |
| Vascular disorders | ||
| Hypertensive crisis | 1/52 (1.9%) | 1 |
| Hypotension | 1/52 (1.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Enzalutimide | ||
| Affected / at Risk (%) | # Events | |
| Total | 33/52 (63.5%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 4/52 (7.7%) | 6 |
| Gastrointestinal disorders | ||
| Constipation | 5/52 (9.6%) | 7 |
| Diarrhoea | 5/52 (9.6%) | 8 |
| Dyspepsia | 3/52 (5.8%) | 3 |
| Nausea | 4/52 (7.7%) | 4 |
| Vomiting | 3/52 (5.8%) | 4 |
| General disorders | ||
| Fatigue | 14/52 (26.9%) | 21 |
| Investigations | ||
| Weight decreased | 4/52 (7.7%) | 4 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 6/52 (11.5%) | 6 |
| Hyperglycaemia | 4/52 (7.7%) | 4 |
| Hypoalbuminaemia | 4/52 (7.7%) | 9 |
| Hyponatraemia | 5/52 (9.6%) | 6 |
| Hypophosphataemia | 4/52 (7.7%) | 8 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 7/52 (13.5%) | 7 |
| Back pain | 7/52 (13.5%) | 8 |
| Bone pain | 3/52 (5.8%) | 3 |
| Muscular weakness | 4/52 (7.7%) | 7 |
| Musculoskeletal pain | 3/52 (5.8%) | 3 |
| Nervous system disorders | ||
| Headache | 3/52 (5.8%) | 4 |
| Renal and urinary disorders | ||
| Pollakiuria | 3/52 (5.8%) | 3 |
| Urinary incontinence | 3/52 (5.8%) | 3 |
| Vascular disorders | ||
| Hot flush | 6/52 (11.5%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. The sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
| Name/Title | Clinical Trial Disclosure |
|---|---|
| Organization | Astellas Pharma Europe B.V. (APEB) |
| Phone | 800-888-7704 Ext:5473 |
| astellas.resultsdisclosure@astellas.com |
- 9785-CL-0121