| Eligibility |
Inclusion Criteria:
- Written informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of >= 52 weeks.
- Hemoglobin >= 11.0 g/dL.
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3).
- Platelet count >= 100 x 10^9/L (>100,000 per mm^3).
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not
apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician.
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT]/alanine aminotransferase [ALT] serum glutamate pyruvate transaminase [SGPT]) =<
2.5 x institutional upper limit of normal.
- Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula (Cockcroft
and Gault 1976) or by 24-hour urine collection for determination of creatinine
clearance.
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
- Consent to MD Anderson laboratory protocol PA13-0291 and LAB02-152.
- Willing to have peripheral blood mononuclear cells and bone marrow biopsies to be
collected prior to receiving the first dose of durvalumab and tremelimumab, after
2-doses and 4-doses of durvalumab and tremelimumab, after 2nd treatment administration
and 4th treatment administration.
- Histologically or cytologically confirmed adenocarcinoma of the prostate.
- Evidence of metastatic disease to the bone seen on most recent bone scan, computed
tomography (CT) scan and/or magnetic resonance imaging (MRI).
- Asymptomatic or minimally symptomatic patients (do not require narcotics for prostate
cancer-related pain).
- Tumor progression while on hormone therapy with castrate levels serum testosterone (=<
1.7 nmol/L or 50 ng/dL) defined by prostate-specific antigen (PSA) and/or radiographic
criteria according to the Prostate Cancer Working Group 3 (PCWG3). Castrate levels of
testosterone must be maintained by surgical or medical means throughout the conduct of
the study.
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site), previous enrollment in the present study.
- Participation in another clinical study with an investigational product during the
last 4 weeks.
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an
anti-CTLA4, including tremelimumab.
- History of another primary malignancy except for: 1) Malignancy treated with curative
intent and with no known active disease >= 5 years before the first dose of study drug
and of low potential risk for recurrence. 2) Adequately treated non-melanoma skin
cancer or lentigo maligna without evidence of disease. 3) Adequately treated carcinoma
in situ without evidence of disease (e.g., superficial bladder cancer).
- Evidence of visceral metastasis to the liver.
- Prior use of taxane-based chemotherapy for treatment of castrate resistant prostate
cancer.
- Receipt of the last dose of anti-cancer therapy (immunotherapy, endocrine therapy
[e.g., abiraterone acetate, enzalutamide], targeted therapy, biologic therapy, tumor
embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to
the first dose of study drug. (with the exception of any previous treatment with a PD1
or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.)
- Major surgical procedure (as defined by the investigator) within 28 days prior to the
first dose of durvalumab or tremelimumab. Note: Local surgery of isolated lesions for
palliative intent is acceptable.
- QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms. Any
clinically significant abnormalities detected, require triplicate electrocardiogram
(ECG) results and a mean QT interval corrected for heart rate using Fridericia's
formula (QTcF) >= 470 ms calculated from 3 electrocardiograms (ECGs).
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab or tremelimumab, with the exceptions of: intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid or steroids as
pre-medication for hypersensitivity reactions (e.g. CT scan premedication).
- Any unresolved toxicity (Common Terminology Criteria for Adverse Events [CTCAE] grade
>= 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is
not reasonably expected to be exacerbated by the investigational product may be
included (e.g., hearing loss, peripherally neuropathy).
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this
criterion:
- Patients with vitiligo or alopecia;
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement;
- Any chronic skin condition that does not require systemic therapy;
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician;
- Patients with celiac disease controlled by diet alone.
- Subjects with history of diverticulitis may be included only after consultation
and approval of the study physician.
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- History of hypersensitivity to the combination of durvalumab and tremelimumab.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diathesis including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent.
- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS). Known history of positive test for
hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for
hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test
indicating acute or chronic infection.
- History of leptomeningeal carcinomatosis.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab or tremelimumab.
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.
- Brain metastases or spinal cord compression unless asymptomatic or treated and stable
off steroids and anti-convulsants for at least 28 days prior to study treatment start.
Patients with suspected brain metastases at screening should have a CT/MRI of the
brain prior to study entry.
- Subjects with uncontrolled seizures.
- Male patients of reproductive potential who are not willing to employ effective birth
control from screening to 180 days after the last dose of durvalumab + tremelimumab
combination therapy or 90 days after the last dose of durvalumab monotherapy,
whichever is the longer time period.
- A malignancy [other than the one treated in this study] which required radiotherapy or
systemic treatment within the past 5 years, or has a >= 30% probability of recurrence
within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)
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