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New treatment option for Prostate Adenocarcinoma
Official title Neoadjuvant Atezolizumab-Based Combination Therapy in Men With Localized Prostate Cancer Prior to Radical Prostatectomy
ClinicalTrials.gov ID: NCT03821246
What this study is testing
What is Atezolizumab?
Atezolizumab is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for prostate adenocarcinoma.
Also referred to as MPDL 3280A, MPDL 328OA.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase II trial studies how well atezolizumab works alone or in combination with etrumadenant or tocilizumab in treating men with localized prostate cancer before radical prostatectomy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older, men only
You may be able to join if
- Histologically confirmed adenocarcinoma of the prostate. a. people with small cell or neuroendocrine PC are not eligible.
- Eligible for radical prostatectomy as determined by urologic oncology surgeon, and subject consents to proceeding with radical prostatectomy. a...
- Only patients with high-risk disease are eligible for the safety lead-in for each cohort. Patients with intermediate-risk disease will be included...
- Availability of a representative tumor specimen that is suitable for the planned study analyses, as determined by the Principal Investigator.
- A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut...
You likely can't join if
- Age \>= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Requirements for organ and marrow function:
- Hemoglobin \>= 9 g/dL
- \- Participants must not have been transfused within 2 weeks prior to screening to meet this criterion
- Absolute neutrophil count \>= 1,500/microliter (uL) without granulocyte colonystimulating factor support
See the full eligibility criteria
Who can join
- Histologically confirmed adenocarcinoma of the prostate. a. people with small cell or neuroendocrine PC are not eligible.
- Eligible for radical prostatectomy as determined by urologic oncology surgeon, and subject consents to proceeding with radical prostatectomy. a. Deemed by urologic oncology surgeon to be appropriate for a...
- Only patients with high-risk disease are eligible for the safety lead-in for each cohort. Patients with intermediate-risk disease will be included after interim analyses is complete for the corresponding cohort and the...
- Availability of a representative tumor specimen that is suitable for the planned study analyses, as determined by the Principal Investigator.
- A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology...
- If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Refer to Section 6.3 for additional information on...
- people have not received any prior systemic or locally directed therapy for PC (see
What rules you out
- Age \>= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Requirements for organ and marrow function:
- Hemoglobin \>= 9 g/dL
- \- Participants must not have been transfused within 2 weeks prior to screening to meet this criterion
- Absolute neutrophil count \>= 1,500/microliter (uL) without granulocyte colonystimulating factor support
- Absolute lymphocyte count \>= 500/uL
- Platelets \>= 100,000/uL without transfusion
- Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (known Gilbert disease: \< 3 x ULN)
- Alkaline phosphatase \< 2 x institutional ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) =\< 2 x institutional ULN
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2 x institutional ULN
- International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \< 1.5 x institutional ULN for people not receiving therapeutic anticoagulation
- Creatinine clearance \>= 30 mL/min (calculated using the Cockcroft-Gault formula)
- Serum creatinine \ 30
- Testosterone level \> 150 ng/dL.
- Contraception: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm as defined below:
- With female partners of childbearing potential: men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and...
- With pregnant female partners: men must remain abstinent or use a condom during the treatment period and for 4 months after the last dose of study treatment to avoid exposing the embryo
- Abstinence: the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar...
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen \> 3 months.
- Ability to understand a written informed consent document, and the willingness to sign it.
- Ability to comply with the study protocol, in the investigator's judgment. Exclusion Criteria:
- Evidence of metastatic disease as determined by standard staging scans. a. Staging scans should be performed per urologic standard of care for patients undergoing radical prostatectomy [per American Urological...
- Not a candidate for radical prostatectomy as determined by treating urologic oncology surgeon.
- Any prior systemic therapy for PC, including antiandrogens, androgen deprivation therapy [gonadotropin-releasing hormone (GnRH) agonist or antagonist], chemotherapy, targeted therapy, immunotherapy, OR...
- Prior radiotherapy for PC.
- Any history of prior malignancy, except:
- Non-melanoma skin cancer treated with curative intent
- Carcinoma-in-situ (CIS) treated with curative intent, without evidence of recurrence or disease progression for 3 years
- Appropriately treated Stage I uterine cancer
- All other cancer: treated with curative intent and without evidence of disease on standard of care follow-up for 5 years
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel...
- people with a history of autoimmune-related hypothyroidism who are on thyroid-replacement therapy, with a stable dose \> 3 months, are eligible for the study
- people with controlled type 1 diabetes mellitus who are on an insulin regimen, with a Glycated hemoglobin (hemoglobin A1C) \< 7.0 are eligible for the study. All people with controlled type 2 diabetes mellitus are...
- people with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded from the study) are eligible for the study provided all of...
- Rash covers \< 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical steroids
- No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral...
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or any evidence of active, non-infectious pneumonitis requiring...
- History of prior positive human immunodeficiency virus (HIV) test.
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (chronic or acute).
- people with a past or resolved HBV infection are eligible for this study.
- HCV positivity is defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test at screening; the HCV RNA test will only be performed for people who have a positive HCV antibody...
- Significant cardiovascular disease, such as New York Heart Association class III or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment...
- Active chronic obstructive pulmonary disease (COPD) requiring use of home oxygen (O2) or systemic steroid therapy \> 10 mg prednisone (or equivalent) daily.
- Asthma requiring systemic corticosteroids \> 10 mg prednisone (or equivalent) daily. Inhaled corticosteroids for the treatment of asthma are permitted.
- Major surgical procedure (including joint surgery) other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study...
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render...
- Prior allogeneic stem cell or solid organ transplantation.
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study or within 5 months after the last dose of...
- Treatment with investigational therapy within 28 days prior to initiation of study treatment.
- Prior treatment with adenosine-axis inhibitors, cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), ant-PD-1, and...
- Treatment with systemic immunostimulatory agents [including, but not limited to, interferon and interleukin 2 (IL-2)] within 4 weeks or five half-lives of the drug (whichever is longer) prior to initiation of study...
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF)- agents) within 2...
- Patients who receive acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for...
- Patients who receive mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma (=\< 10 mg prednisone or equivalent), or low-dose corticosteroids for...
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
- Known allergy or hypersensitivity to any of the study drugs of their excipients.
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples include: CAMPATH, anti-cluster of differentiation 4 (CD4), anti-cluster of differentiation 5...
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
- Previous treatment with tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the Sponsor-Investigator on a case-by-case basis).
- Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation within 5 years prior to first dose of study treatment.
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
- Evidence of serious uncontrolled concomitant, nervous system, pulmonary, renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative...
- Any history of recent serious bacterial, viral, fungal, or other opportunistic infections.
- Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
- Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial.
- Pregnant women or nursing (breast feeding) mothers.
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.
- Patients with lack of peripheral venous access Additional Exclusion Criteria for Cohort B (atezolizumab + etrumadenant):
- Treatment with known P-glycoprotein (P-gp) substrates with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks (for investigational drugs when half-life is unknown or not accurately...
- Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (eg,clarithromycin, grapefruit juice, itraconazole, ketoconazole...
- Treatment with known breast cancer resistance protein (BCRP) substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks (for investigational drugs when half-life is...
- Known active infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, including, but not limited to, TB (i.e., has signs and symptoms of TB) and atypical mycobacterial disease...
The study team makes the final eligibility decision.
Where it's taking place
- San Francisco, California, United States
- St Louis, Missouri, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling male, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include San Francisco, California, United States; St Louis, Missouri, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.