The objective of this study is to compare the overall survival of patients with castration resistant prostate cancer who have progressed after receiving docetaxel treatment, when they are treated with bone directed radiotherapy plus Ipilimumab…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Congenital reproductive tract and breast disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of this study is overall survival defined as the time from
date of randomisation to the date of death.
Secondary outcome
The secondary outcomes of the study are to assess the time the patient is free
from disease progression and assess how many patients have had a 50% decrease
from baseline in their level of prostate specific antigen.
Background summary
Most, if not all castration resistant prostate cancer patients present with
bone metastases which may be very painful and the bones are at risk of
fractures. These patients receive bone radiotherapy as standard of care to
provide pain relief. Ipilimumab is a class of medicine which attempts to use
the body*s own immune system to stimulate a response to disease. The hypothesis
is that the combination of standard radiotherapy to symptomatic bone metastasis
with Ipilmumab will amplify the immune response generated by the radiotherapy
and result in systemic anti-tumour activity leading to an improvement in the
patient*s overall survival.
Study objective
The objective of this study is to compare the overall survival of patients with
castration resistant prostate cancer who have progressed after receiving
docetaxel treatment, when they are treated with bone directed radiotherapy plus
Ipilimumab compared to patients who are treated with bone directed radiotherapy
plus placebo.
Study design
This study is a randomized, double-blind study which will be conducted in 4
stages;
A screening phase which will last from 1-28 days; an induction phase lasting
approximately 24 weeks, where study medication will be administered on weeks 1,
4. 7 and 10; a maintenance phase where study medication will be administered
every 12 weeks until the patient decides to stop treatment, the patient*s
disease worsens or the patient experiences unacceptable side-effects and can
not continue; a follow up phase to monitor the patient*s survival until the
study ends or the patient decides to withdraw.
Intervention
Ipilmumab is an investigational product in this study. After receiving
radiotherapy, each patient will receive either ipilimumab or placebo
administered by intravenous (IV) infusion which will take about 90 minutes.
Study burden and risks
Burden: study procedures (physical exams, blood sampling, intravenous infusions
of study medication) and regular attendance for hospital visits during the
induction phase of the study, followed by visits every 6 weeks for the first 24
weeks and then every 12 weeks after in the maintenance phase.
Risks: possible adverse events of ipilimumab
Benefit: potential improvement of overall survival.
Group relatedness: knowledge gain from this study may also help other patients
in the future.
Vijzelmolenlaan 9
3447 GX Woerden
NL
Vijzelmolenlaan 9
3447 GX Woerden
NL
Listed location countries
Age
Inclusion criteria
1. Signed Written Informed Consent
a) Willing and able to give informed consent. ;2. Target Population
a) Histologic or cytologic confirmation of adenocarcinoma of the prostate:
b) At least 1 symptomatic bone metastasis which can be irradiated, or at least 1 asymptomatic bone metastasis which, in the clinical judgment of the investigator, is appropriate to be irradiated (eg, risk of fracture or cord compression):
c) Have been treated by orchiectomy or are receiving a GnRH agonist/antagonist, and have a testosterone level less than 50ng/dl:
d) If applicable, must have discontinued anti-androgens at least 2 weeks prior to randomization. Medications considered to be anti-androgens include; Flutamide, Bicalutamide (Casodex), nilutamide, aminoglutethimide, ketoconazole, diethylstilbestrol, megestrol acetate (Megace), and finasteride (Proscar).
Additionally, any natural substance that might have anti-androgen activities, including but not limited to St John*s Wort, Saw Palmetto, or PC-SPES, must be discontinued prior to randomisation;
e) Must have received at least 1 prior regimen containing docetaxel for the treatment of metastatic CRPC consisting of at least 2 cycles of docetaxel.
f) ECOG Performance Status: Subjects must have ECOG PS 0-1.
g) Subjects must have progressed during docetaxel treatment or within 6 months of receiving, a docetaxel-containing regimen. If the subject received an additional anti-cancer therapy after docetaxel, they must also demonstrate signs of progression on that therapy. For eligibility purposes, progressive disease is defined as:
i) Rising PSA values at a minimum of 1-week intervals and a 2.0 ng/ml minimum starting value ii) Progression per bone scan: the appearance of 2 or more new lesions
iii) Progression per target lesions/measurable disease: nodal or visceral disease progression, per modified RECIST. Only lymph nodes greater than 2 cm will be considered to assess a change in size qualifying for disease progression.
3. Age and Sex
a) Men > 18 years of age or minimum age of consent per local regulations.
Exclusion criteria
1) Sex and Reproductive Status
a) Sexually active fertile men not using effective birth control if their partners are women of child-bearing potential (WOCBP).
2) Target Disease Exceptions
a) Subjects with radiological evidence of brain metastasis.
3) Medical History and Concurrent Diseases
a) Autoimmune disease: subjects with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn*s disease are excluded from this study, as are subjects with a history of rheumatoid arthritis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis
(eg, Wegener*s Granulomatosis);
b) Motor neuropathy considered of autoimmune origin (eg, Guillain-Barre
Syndrome);
c) Patients with a prior history of pelvic (prostate) radiation associated with significant radiation proctitis within 12 months prior to the planned first infusion of blinded study drug. For the purpose of this protocol, radiation proctitis is defined as diarrhoea that reached a level of Grade 2 or Grade 3, that occurred within 1 month of radiation treatment, and that was of 7 days duration or longer.
d) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing questionnaires;
e) A serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol therapy;
f) Any other malignancy from which the subject has been disease-free for less than
5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, or superficial bladder cancer;
g) Known HIV or Hepatitis B or Hepatitis C infection.
4) Physical and Laboratory Test Findings
a) Inadequate hematologic function defined by an absolute neutrophil count (ANC)
< 1,500/mm3, a platelet count < 100,000/mm3, or a haemoglobin level < 9 g/dL;
b) Inadequate hepatic function defined by a total bilirubin level * 2.5 times the upper limit of normal (ULN), AST and ALT levels * 2.5 times the ULN or * 5 times the
ULN if liver metastases are present;
c) Inadequate renal function defined by a serum creatinine level * 2.5 times the
ULN;
d) Inadequate creatinine clearance defined as less than 50 mL/min;
e) Usage of greater than 120 mg of morphine (or equivalent) over a 24 hour period within 3 days of randomization, unless narcotic usage is necessitated by a symptomatic bone lesion that is likely to be palliated by protocol-specified radiotherapy.
5) Prohibited Treatments and/or Therapies
a) More than 2 prior systemic anti-cancer regimens (including re-treatment with
docetaxel) for metastatic CRPC;
b) Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, or adrenal insufficiencies, or if administered at doses of prednisone 5 mg BID or equivalent;
c) Any non-oncology vaccine therapy used for the prevention of infectious diseases (for up to 4 weeks prior to or after any dose of blinded study drug);
d) Prior treatment with any inhibitor or agonist of T cell costimulation;
e) Prior strontium or samarium;
f) Prior treatment on BMS study CA180227: A Randomized Double-Blind
Phase 3 Trial Comparing Docetaxel Combined with Dasatinib to Docetaxel Combined with Placebo in Castration-Resistant Prostate Cancer.
6) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated;
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
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 |
---|---|
EudraCT | EUCTR2008-003314-97-NL |
ClinicalTrials.gov | NCT-00861614 |
CCMO | NL28137.029.09 |