Castration-Resistant Prostate Cancer (CRPC)
Conditions
Keywords
Prostate Cancer, Castration-Resistant Prostate Cancer (CRPC), MDV3100, Androgen receptor signaling inhibitor
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.
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.
Interventions
DRUGEnzalutamide
Oral
Sponsors
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Astellas Pharma Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. 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. 2. Subject has a history of loss of consciousness or transient ischemic attack within 12 months prior to Day 1 of the completed preceding study. 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Moldova, South Africa, United States
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 details
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 \[NCT02225093\]).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 52 |
| Total | 52 |
Baseline characteristics
| Characteristic | Enzalutamide |
|---|---|
| Age, Continuous | 68.6 years STANDARD_DEVIATION 7.39 |
| Distant Metastasis at Initial Diagnosis M0 - No Distant Metastasis | 12 Participants |
| Distant Metastasis at Initial Diagnosis M1 - Distant Metastasis | 9 Participants |
| Distant Metastasis at Initial Diagnosis MX - Distant Metastasis Cannot be Assessed | 8 Participants |
| Distant Metastasis at Initial Diagnosis Unknown | 23 Participants |
| Duration of Prostate Cancer | 69.4 months STANDARD_DEVIATION 64.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Pathologic Tumor Stage (pT) pT2 - Organ Confined | 5 Participants |
| Pathologic Tumor Stage (pT) pT3 - Extraprostatic Extension | 9 Participants |
| Pathologic Tumor Stage (pT) pT4 - Invasion of Bladder, Rectum | 1 Participants |
| Pathologic Tumor Stage (pT) Unknown | 37 Participants |
| Primary Gleason Score at Initial Diagnosis Score 3 | 15 Participants |
| Primary Gleason Score at Initial Diagnosis Score 4 | 13 Participants |
| Primary Gleason Score at Initial Diagnosis Score 5 | 4 Participants |
| Primary Gleason Score at Initial Diagnosis Unknown | 20 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) T0 - No Evidence of Primary Tumor | 1 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) T1 - Clinically Tumor Not Palpable or Visible | 1 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) T2 - Tumor Confined Within the Prostate | 8 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) T3 - Tumor Extends Through the Prostatic Capsule | 13 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) T4 - Tumor Fixed or Invades Adjacent Structures | 3 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) TX - Primary Tumor Cannot be Assessed | 3 Participants |
| Primary Tumor Assessment at Initial Diagnosis - Clinical Tumor Stage (T) Unknown | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis N0 - No Regional Lymph Node Metastasis | 15 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis N1 - Metastasis in Regional Lymph Node(s) | 6 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis NX - Regional Lymph Nodes Were Not Assessed | 18 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis pN0 - No Positive Regional Nodes | 6 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis pN1 - Metastasis in Regional Nodes(s) | 2 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis pNX - Regional Lymph Nodes Not Sampled | 8 Participants |
| Regional Lymph Nodes (N) at Initial Diagnosis Unknown | 36 Participants |
| Secondary Gleason Score at Initial Diagnosis Score 3 | 9 Participants |
| Secondary Gleason Score at Initial Diagnosis Score 4 | 14 Participants |
| Secondary Gleason Score at Initial Diagnosis Score 5 | 9 Participants |
| Secondary Gleason Score at Initial Diagnosis Unknown | 20 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 52 Participants |
| Total Gleason Score at Initial Diagnosis Score 6 | 5 Participants |
| Total Gleason Score at Initial Diagnosis Score 7 | 16 Participants |
| Total Gleason Score at Initial Diagnosis Score 8 | 1 Participants |
| Total Gleason Score at Initial Diagnosis Score 9 | 13 Participants |
| Total Gleason Score at Initial Diagnosis Unknown | 17 Participants |
| Treatment Duration in Extension Study >= 182 - <365 | 9 Days |
| Treatment Duration in Extension Study >= 365 | 27 Days |
| Treatment Duration in Extension Study <= 60 | 4 Days |
| Treatment Duration in Extension Study > 60 - <182 | 12 Days |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 52 |
| other Total, other adverse events | 33 / 52 |
| serious Total, serious adverse events | 17 / 52 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
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
Population: The analysis population was the SAF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzalutamide | Number of Participants With Adverse Events (AEs) | Any TEAE | 43 Participants |
| Enzalutamide | Number of Participants With Adverse Events (AEs) | Drug-Related TEAEs | 27 Participants |
| Enzalutamide | Number of Participants With Adverse Events (AEs) | Deaths | 5 Participants |
| Enzalutamide | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 17 Participants |
| Enzalutamide | Number of Participants With Adverse Events (AEs) | Drug-Related Serious TEAEs | 5 Participants |
| Enzalutamide | Number of Participants With Adverse Events (AEs) | TEAEs Leading to Study Drug Discontinuation | 12 Participants |
| Enzalutamide | Number of Participants With Adverse Events (AEs) | Drug-Related TEAEs Lead to Study Discontinuation | 5 Participants |