This study has been transitioned to CTIS with ID 2023-509221-47-00 check the CTIS register for the current data. To demonstrate superiority in the metastasis-free survival (MFS) of men with high risk NM-CRPC treated with apalutamide versus…
ID
Source
Brief title
Condition
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Metastasis-Free Survival (MFS)
Secondary outcome
Secondary Endpoints
* Time to Metastasis (TTM)
* PFS
* Time to symptomatic progression
* Overall survival (OS)
* Time to initiation of cytotoxic chemotherapy
Other Evaluations
* Health-related quality of life and prostate cancer-specific symptoms
* Type, incidence, severity, timing, seriousness, and relatedness of adverse
events and laboratory abnormalities
* PSA Response
* Time to PSA progression
* Population PK
* Assessment of ventricular repolarization
* Second progression-free survival (PFS2)
* Medical resource utilization (MRU)
Background summary
See protocol 24- Section 1. Background
Study objective
This study has been transitioned to CTIS with ID 2023-509221-47-00 check the CTIS register for the current data.
To demonstrate superiority in the metastasis-free survival (MFS) of men with
high risk NM-CRPC treated with apalutamide versus placebo
Secondary Objective:
To compare the overall survival (OS) of men with high risk NM-CRPC treated with
apalutamide versus placebo
To compare the time to symptomatic progression in men with high risk NM-CRPC
treated with apalutamide versus placebo
To compare the time to initiation of cytotoxic chemotherapy in men with high
risk NM-CRPC treated with apalutamide versus placebo
To compare the progression-free survival (PFS) of men with high risk NM-CRPC
treated with apalutamide versus placebo
To compare the time to metastasis (TTM) in men with high risk NM-CRPC treated
with apalutamide versus placebo
To evaluate the safety and tolerability of apalutamide
Other Objectives
To compare patient reported outcomes (PROs) of health-related quality of life
and prostate cancer-specific symptoms in men with high risk NM-CRPC treated
with apalutamide versus placebo
To evaluate the population pharmacokinetics (PK) of apalutamide
To evaluate the effect of apalutamide on ventricular repolarization in a subset
of patients from selected clinical sites
To evaluate exploratory biomarkers predictive of response and resistance to
apalutamide treatment
Study design
This is a randomized (2:1), multicenter, double-blind, placebo-controlled,
Phase III clinical trial evaluating the efficacy and safety of apalutamide
versus placebo in men with high risk (M0) NM-CRPC, defined as PSA Doubling Time
(PSADT) <= 10 months. Patients will be stratified based on: - PSADT: > 6
months vs. <= 6 months - Bone-sparing agent use: Yes vs. No - Loco-regional
disease: N0 vs. N1 Patients will be followed for safety and efficacy as per the
schedule of activities and will remain on study treatment until documented
radiographic progression (development of distant metastases as assessed by
blinded independent central review) or the development of unacceptable
toxicity. Patients discontinuing treatment due to documented radiographic
progression will enter the survival follow-up period, where they will be
followed for the development of symptomatic progression and initiation of
subsequent anti-cancer therapies (in particular, cytotoxic chemotherapy) every
4 months until death, loss of followup, or withdrawal of consent, whichever
comes first. Patients discontinuing treatment prior to documented radiographic
progression will also enter the survival follow-up period where they will
continue to have scheduled disease assessments every 4 months until documented
radiographic progression, and will be followed for the development of
symptomatic progression and initiation of subsequent anti-cancer therapies (in
particular, cytotoxic chemotherapy) every 4 months until death, loss of follow
up, or withdrawal of consent, whichever comes first. At the time of study
unblinding and in the event of a positive study result, all subjects currently
receiving placebo will have the opportunity to receive active therapy with
apalutamide.
Intervention
apalutamide/matched placebo tablets will be administered orally on a continuous
daily dosing regimen, at a starting dose for apalutamide of
240 mg once daily (4 x 60-mg tablets). The only difference between apalutamide
and its matched placebo is the absence of the active
ingredient in the matched placebo.
Study burden and risks
At this time around 500 patients have been treated with apalutamide. Risks and
side effects that may be possibly related to apalutamide include: Very Common
(>10%) Fatigue Skin rash Joint pain (Arthralgia) Weight loss Fall Fracture
Common (1- 10%) Itching Changes in thyroid function (Hypothyroidism) Increase
in cholesterol Increase in triglycerides Very Rare (<1%) Seizure Seizures
have been observed very rarely in subjects taking part in apalutamide studies.
The doctor will confirm that the patient has no history of seizure and will
check throughout the study that the patient is not taking other medications
that can increase a risk of seizures. The patient must inform the doctor of all
medications he is taking and any changes in medications. If the patient thinks
he might have had a seizure, or convulsion, or have lost consciousness (passed
out), he must let his doctor know right away. More than 1 in 10 patients have
developed a rash. Some rashes may need medical attention. The rash may be
confined to one area of the body or may spread across the body. The patient
must contact his doctor at the first sign of rash or any symptoms of rash (like
itching) during the study. Rashes that are painful, blisters on or near the
lips, eyes or genitals may need immediate evaluation by the doctor. The patient
may be given medicines to apply to his skin or take by mouth to help the signs
and symptoms of rash. Also the study medication may be temporarily held.
Wilshire Blvd 10990, Suite 440
Los Angeles, CA 90024
US
Wilshire Blvd 10990, Suite 440
Los Angeles, CA 90024
US
Listed location countries
Age
Inclusion criteria
1. Criterion modified per amendment. 1.2 Histologically or cytologically
confirmed adenocarcinoma of the prostate without neuroendocrine differentiation
or small cell features, with high risk for development of metastases, defined
as PSADT <= 10 months. PSADT is calculated using at least 3 PSA values obtained
during continuous ADT. (see Section 5.1). 2. Criterion modified per amendment
2.1 Castration-resistant prostate cancer demonstrated during continuous ADT,
defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mL 3.
Criterion modified per amendment 3.1. Criterion modified per amendment 3.2
Surgically or medically castrated, with testosterone levels of <50 ng/dL. If
the patient is medically castrated, continuous dosing with GnRHa must have been
initiated at least 4 weeks prior to randomization and must be continued
throughout the study to maintain castrate levels of testosterone. 4. Criterion
modified per amendment 4.1 Patients receiving bone loss prevention treatment
with bone-sparing agents indicated for the treatment of osteoporosis at doses
and dosing schedule appropriate for the treatment of osteoporosis (e.g.,
denosumab [Prolia®], zoledronic acid [Reclast®]) must be on stable doses for at
least 4 weeks prior to randomization. 5. Criterion modified per amendment 5.2
Patients who received a first generation anti-androgen (e.g., bicalutamide,
flutamide, nilutamide) must have at least a 4-week washout prior to
randomization AND must show continuing disease (PSA) progression (an increase
in PSA) after washout. 6. Criterion modified per amendment 6.2 At least 4 weeks
must have elapsed from the use of 5-α reductase inhibitors (e.g., dutasteride,
finasteride), estrogens (irrespective of dose used), and any other anti-cancer
therapy prior to randomization, including chemotherapy given in the
adjuvant/neoadjuvant setting (e.g., clinical trial) 7. At least 4 weeks must
have elapsed from major surgery or radiation therapy prior to randomization 8.
Age >= 18 years 9. Eastern Cooperative Oncology Group (ECOG) Performance Status
grade 0 or 1 10. Resolution of all acute toxic effects of prior therapy or
surgical procedure to Grade 1 or baseline prior to randomization 11. Criterion
modified per amendment 11.1 Criterion modified per amendment 11.2 Adequate
organ function as defined by the following criteria: * Serum aspartate
transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum
alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) <= 2.5 x
upper limit of normal (ULN) * Total serum bilirubin <=1.5 x ULN. Total serum
bilirubin >1.5 x ULN is allowed if Gilbert*s disease is documented prior to
screening. * Serum creatinine <= 2 x ULN * Absolute neutrophil count (ANC) >=
1500/µL * Platelets >= 100,000/µL * Hemoglobin >= 9.0 g/dL o Administration of
growth factors or blood transfusions will not be allowed within 4 weeks of the
hematology labs required to confirm eligibility 12. Signed and dated informed
consent document indicating that the patient (or legally acceptable
representative) has been informed of all pertinent aspects of the trial prior
to randomization 13. Criterion modified per amendment 13.1 Willingness and
ability to comply with scheduled visits, treatment plans, laboratory and
radiographic assessments, and other study procedures, including ability to
swallow large study drug tablets, the completion of patient reported outcomes
questionnaires and long-term survival follow-up visits
Exclusion criteria
1. Criterion modified per amendment 1.1 Presence of distant metastases
confirmed by blinded independent central review (BICR), including CNS and
vertebral or meningeal involvement, or history of distant metastases.
Exception: Pelvic lymph nodes <2 cm in short axis (N1) located below the
iliac bifurcation are allowed 2. Symptomatic loco-regional disease requiring
medical intervention, such as moderate or severe urinary obstruction or
hydronephrosis, due to primary tumor (e.g., tumor obstruction of bladder
trigone) 3. Prior treatment with second generation anti-androgens (e.g.,
enzalutamide) 4. Criterion modified per amendment 4.1 Prior treatment with
CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galerterone,
ketoconazole, aminoglutethimide) 5. Prior treatment with radiopharmaceutical
agents (e.g., Strontium-89), immunotherapy (e.g., sipuleucel-T), or any other
investigational agent for NM-CRPC 6. Prior chemotherapy for prostate cancer,
except if administered in the adjuvant/neoadjuvant setting 7. History of
seizure or condition that may pre-dispose to seizure (e.g., prior stroke within
1 year prior to randomization, brain arteriovenous malformation, Schwannoma,
meningioma, or other benign CNS or meningeal disease which may require
treatment with surgery or radiation therapy) 8. Criterion modified per
amendment 8.1 Criterion modified per amendment 8.2 Concurrent therapy with any
of the following (all must have been discontinued or substituted for at least 4
weeks prior to randomization): * Medications known to lower the seizure
threshold (for a complete list please see Appendix 5) * Herbal (i.e., saw
palmetto) and non-herbal products (i.e., pomegranate) that may decrease PSA
levels * Systemic (oral/IV/IM) corticosteroids. Short term use (<= 4 weeks) of
corticosteroids during the study is allowed if clinically indicated, but it
should be tapered off as soon as possible * Any other experimental treatment on
another clinical trial * Agents indicated for the prevention of
skeletal-related events in patients with solid tumors (e.g., denosumab
[Xgeva®]) 9. Criterion modified per amendment 9.1 Criterion modified per
amendment 9.2 History or evidence of any of the following conditions: - Any
prior malignancy (other than adequately treated basal cell or squamous cell
skin cancer, superficial bladder cancer, or any other cancer in situ currently
in complete remission) within 5 years prior to randomization * Any of the
following within 6 months prior to randomization:Severe/unstable angina,
myocardial infarction, symptomatic congestive heart failure, arterial or venous
thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident
including transient ischemic attacks), or clinically significant ventricular
arrhythmias - Uncontrolled hypertension (systolic blood pressure >=160 mmHg or
diastolic BP >=100 mmHg). Patients with a history of uncontrolled hypertension
are allowed provided blood pressure is controlled by anti-hypertensive
treatment. -Gastrointestinal disorder affecting absorption -Active infection,
such as human immunodeficiency virus (HIV) - Any other condition that, in the
opinion of the Investigator, would impair the patient*s ability to comply with
study procedures.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-509221-47-00 |
| EudraCT | EUCTR2012-004322-24-NL |
| ClinicalTrials.gov | NCT01946204 |
| CCMO | NL43395.060.13 |