phase iii study of dcvac/pca added to standard chemotherapy for men with metastatic castration resistant prostate cancer

Conditions: Metastatic Castration-resistant Prostate Cancer

Summary: the viable study sought to confirm the hypothesis that the combination of docetaxel with dcvac/pca followed by a maintenance therapy with dcvac/pca would improve overall survival in patients with metastatic castration-resistant prostate cancer.

this was a randomized, double blind, placebo-controlled, multicenter, international, parallel-group phase iii study. patients with metastatic castration-resistant prostate cancer who were candidates to receive standard of care first-line chemotherapy with docetaxel plus prednisone were randomized 2:1 into one of two arms: an investigational arm (dcvac/pca) and a control arm (placebo) in addition to chemotherapy (docetaxel plus prednisone).

Eligibility criteria:
inclusion criteria: * male 18 years and older. * histologically or cytologically confirmed prostate adenocarcinoma. * presence of skeletal, or soft-tissue/visceral/nodal metastases according to one of the following criteria: * confirmed pathological fracture related to the disease or * confirmation of distant bone and/or soft-tissue and/or visceral metastases on ct or mri scan or bone scintigraphy or * positive pathology report of metastatic lesion * disease progression despite androgen-deprivation therapy (adt) as indicated by: * prostate-specific antigen (psa) increase that is ≥ 2 ng/ml and ≥ 25% above the minimum psa as reached during adt or above the pre-treatment level, if no response was observed and which is confirmed by a second value 1 or more weeks later or * progression of measurable lymph nodes (short axis ≥ 15 mm) or visceral lesion measurable per recist v1.1 criteria, confirmation by an independent review facility (irf) required or * two or more new lesions appearing on bone scan/imaging compared with a previous scan (confirmation by irf required) * maintenance of castrate conditions: patients, who have not had a surgical orchiectomy, must continue with hormone therapy with gonadotropin releasing hormone/ luteinizing hormone-releasing hormone (gnrh/lhrh) agonists or antagonists to reach levels of serum testosterone of ≤ 1.7 nmol/l (50 ng/dl). the duration of the castration period must be at least 4 months before screening as evidenced by combination of clinical/laboratory data (see section 6.8.1). * laboratory criteria: * white blood cells (wbc) greater than 4,000/mm3 (4.0 x109/l) * neutrophil count greater than 1,500/mm3 (1.5 x109/l). * hemoglobin of at least 10 g/dl (100 g/l). * platelet count of at least 100,000/mm3 (100 x 109/l). * total bilirubin within normal limits (benign hereditary hyperbilirubinemias, e.g. gilbert's syndrome, are permitted). * serum alanine aminotransferase, aspartate aminotransferase, and creatinine \< 1.5x times the upper limit of normal (uln). * life expectancy of at least 6 months based on investigator's judgment. * eastern cooperative oncology group (ecog) performance status 0-2. * at least 4 weeks after surgery or radiotherapy before randomization. * a minimum of 28 days beyond initiation of bisphosphonate or denosumab therapy before randomization. * recovery from primary local surgical treatment, radiotherapy or orchiectomy before randomization. * signed informed consent including patient's ability to comprehend its contents. exclusion criteria: * confirmed brain and/or leptomeningeal metastases (other visceral metastases are acceptable). * current symptomatic spinal cord compression requiring surgery or radiation therapy. * prior chemotherapy for prostate cancer. * patient co-morbidities: * subjects who are not indicated for chemotherapy treatment with first line standard of care chemotherapy (docetaxel and prednisone). * hiv positive, human t-lymphotropic virus positive. * active hepatitis b (active hepatitis b), active hepatitis c (hcv), active syphilis. * evidence of active bacterial, viral or fungal infection requiring systemic treatment. * clinically significant cardiovascular disease including: * symptomatic congestive heart failure. * unstable angina pectoris. * serious cardiac arrhythmia requiring medication. * uncontrolled hypertension. * myocardial infarction or ventricular arrhythmia or stroke within a 6 months before screening, known left ventricular ejection fraction (lvef) \< 40% or serious cardiac conduction system disorders, if a pacemaker is not present. * pleural and pericardial effusion of any nci ctcae grade. * peripheral neuropathy having a nci ctcae ≥ grade 2. * history of malignant disease (with the exception of non-melanoma skin tumors) in the preceding five years. * active autoimmune disease requiring treatment. * history of severe forms of primary immune deficiencies. * history of anaphylaxis or other serious reaction following vaccination. * known hypersensitivity to any constituent of the dcvac/pca or placebo product. * uncontrolled co-morbidities including, psychiatric or social conditions which, in the investigator's opinion, would prevent participation in the trial. * systemic corticosteroids at doses greater than 40 mg hydrocortisone daily or equivalent for any reason other than treatment of pca within 6 months before randomization. * ongoing systemic immunosuppressive therapy for any reason. * treatment with anti-androgens, inhibitors of adrenal-produced androgens or other hormonal tumor-focused treatment performed on the day of randomization (except for gnrh/lhrh agonists or antagonists) to exclude possible anti-androgen withdrawal response. this criterion is not applicable to subjects who have never responded to anti-androgen treatment, as there is no risk of anti-androgen withdrawal response. * treatment with immunotherapy against pca within 6 months before randomization. * treatment with radiopharmaceutical within 8 weeks before randomization. * participation in a clinical trial using non-immunological experimental therapy within 4 weeks before randomization. * participation in a clinical trial using immunological experimental therapy (e.g., monoclonal antibodies, cytokines or active cellular immunotherapies) within 6 months before randomization. * refusal to sign the informed consent.

Keywords: immunotherapy metastatic castration-resistant prostate cancer biological vaccine