A Study of Olaparib and Durvalumab in Prostate Cancer

Conditions:Prostate Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:March 7, 2019
End Date:February 2021
Contact:Karen Autio, MD, MSc

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A Phase II Study of Olaparib and Durvalumab in Men With Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer Harboring Mutations in DNA Damage Repair

The purpose of this study is to determine if the combination of olaparib and durvalumab are
better than the standard of care for treating prostate cancer.

Inclusion Criteria:

- Willing and able to provide written informed consent and HIPAA authorization for the
release of personal health information. A signed informed consent must be obtained
before screening procedures are performed.

NOTE: HIPAA authorization may be either included in the informed consent or obtained

- Males 18 years of age and above

- Body weight > 30kg

- History of radical prostatectomy

- Histologically confirmed prostate cancer with progressive disease defined as:

- Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3
PSA determinations obtained at least 1 week apart). The 50% rise in PSA is across the
3 determinations, and these determinations do not need to be sequential.

- PSA doubling time of Kettering Cancer Center nomogram

- No evidence of metastatic disease on conventional imaging (CT/MRI and bone scan).
However, subjects with pelvic and/or retroperitoneal nodes < 2cm in the short axis
will be permitted on study, as they are considered not to have definitive metastases.
(Note: Metastatic disease on investigational imaging, Prostate Specific Membrane
Antigen-targeted (PSMA) PET, PET-choline, or other novel PET tracers who do not have
evidence of metastatic disease using conventional imaging (CT/MRI, bone scan) are

- Molecular evidence of DDR deleterious mutations (somatic or germline), including
BRCA1, BRCA2, ATM, CHEK2, FANCA, RAD51C, RAD51D, PALB2, or CDK12. Mutations may be
truncating, splice site mutations, missense or homozygous deletions. Mutation status
is determined by a local laboratory with the result documented in the subject's
medical record, previously obtained genomic testing from a CLIA-certified lab, or via
archival or fresh tissue.

- ECOG status of ≤1

- Normal organ function with acceptable initial laboratory values within 14 days of
treatment start:

- WBC ≥ 2000/ul

- ANC ≥ 1500/uL

- Hemoglobin ≥ 10g/dL

- Platelet count ≥100,000/ul

- Creatinine Clearance ≥ 51 mL/min estimated using the Cockcroft-Gault equation

- Bilirubin ≤ 1.5 ULN (unless documented Gilbert's disease)

- SGOT (AST) ≤ 2.5 x ULN (unless liver metastases are present, in which case AST must be
5 x ULN)

- SGPT (ALT) ≤ 2.5 x ULN (unless liver metastases are present, in which case ALT must be
5 x ULN)

- Non-castrate level of testosterone defined as a value ≥ 150 ng/dL

- Life expectancy of ≥ 52 weeks.

- Agree to use two medically acceptable, highly effective forms of birth control (e.g.,
spermicide in conjunction with a barrier such as a condom) or sexual abstinence for
the duration of the study, including 180 days after the last dose of study drug. Sperm
donation is prohibited during the study and for 3 months after the last dose of study
drug. Female partners of child bearing potential should use hormonal or barrier
contraception unless postmenopausal or abstinent.

Exclusion Criteria:

- No other malignancy from which the subject has been disease-free for less than 3
years, with the exception of adequately treated and cured non-invasive malignancies
such as basal or squamous cell skin cancer or superficial bladder cancer.

- Less than one month prior to treatment start from last prior regimen or radiation
exposure. Prior radiotherapy to the prostate (adjuvant or salvage radiotherapy) is

- No prior investigational use with an anti-PD(1) including durvalumab or anti-CTLA4

- No prior treatment with a PARP inhibitor, including olaparib.

- No concomitant or prior therapy with any of the following: IL-2, interferon, or other
non-study immunotherapy regimens; immunosuppressive agents; or chronic use of systemic
corticosteroids within 6 weeks of treatment start. Exceptions include:

intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular
injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day
ofprednisone or its equivalent; Steroids as premedication for hypersensitivity reactions
(e.g., CT scan premedication)

- No receipt of live attenuated vaccine within 30 days prior to treatment start Note:
enrolled subjects should not receive live vaccine while receiving IP and up to 30 days
after the last dose of study therapy

- Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
period prior to treatment start is 2 weeks.

- Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.

- More than 2 cycles of intermittent hormones for the treatment of biochemical
recurrence, with a cycle defined as a period of consistent ADT (generally 3-12 months)
followed by intentional cessation of ADT without re-initiation of ADT until the PSA
rises. Prior ADT in the treatment of localized prostate cancer or with salvage
radiation therapy is allowed.

- No medical conditions such as uncontrolled hypertension, uncontrolled diabetes
mellitus, cardiac disease that would, in the opinion of the investigator, make this
protocol unreasonably hazardous.

- Subjects considered a poor medical risk due to a serious, uncontrolled medical
disorder or non-malignant systemic disease. Examples include, but are not limited to,
uncontrolled ventricular arrhythmia, myocardial infarction within 3 months of
treatment start, uncontrolled major seizure disorder, unstable spinal cord
compression, superior vena cava syndrome, extensive interstitial bilateral lung
disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder
that prohibits obtaining informed consent.

- No active infection including tuberculosis (TB) (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and TB testing in
line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)
result), hepatitis C, or active infection with human immunodeficiency virus (positive
HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as
presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV RNA

- No autoimmune disease: subjects with a history of inflammatory bowel disease,
including ulcerative colitis and Crohn's Disease, are excluded from this study, as are
subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis *e.g., Sarcoidosis syndrome or Wegener's granulomatosis with
polyangiitis+); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre
syndrome and myasthenia gravis); Graves' disease. Exceptions include history of
eczema, vitiligo, alopecia, hypothyroidism (e.g., following Hashimoto syndrome) , and
any chronic skin condition that does not require systemic therapy; subjects without
active disease in the last 5 years prior to treatment start may be included but only
after consultation with the treating physician. Exceptions may be made on a case by
case basis upon discussion with the Sponsor Principal Investigator.

- No history of active primary immunodeficiency

- No major surgery within 4 weeks of treatment start. Subjects must have recovered from
any significant effects of any major surgery but investigators may discuss with the
Sponsor Principal Investigator in the case of any exceptions.

- No blood transfusion within 28 days of treatment start.

- Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or
family history of long QT syndrome

- Enrollment in another clinical trial with a therapeutic agent. Subjects may co-enroll
on investigational imaging studies (e.g., PSMA PET) or correlative trials.

- No previous allogeneic bone marrow transplant or double umbilical cord blood

- No history of leptomeningeal carcinomatosis

- No unresolved toxicity (Common Terminology Criteria for Adverse Event (CTCAE) Grade
>/= 2) caused by previous anticancer therapy, excluding alopecia, vitiligo, and the
laboratory values described in the inclusion criteria. Subjects with Grade >/= 2
neuropathy will be evaluated on a case-by-case basis after consultation with the
Sponsor Principal Investigator. Subjects with irreversible toxicity not reasonably
expected to be exacerbated by treatment with study drugs may be included only after
consultation with the Sponsor Principal Investigator

- No subjects who are HIV-positive on combination antiretroviral therapy because of the
potential for pharmacokinetic interactions with olaparib. In addition, these subjects
are at increased risk of lethal infections when treated with marrow suppressive

- No subjects with baseline moderate to severe hepatic impairment (Child-Pugh Class B
and C).

- No subjects with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of MDS/AML.

- No known allergy to any of the compounds under investigation or excipients of the

- Subjects unable to swallow orally administered medication and subjects with
gastrointestinal disorders likely to interfere with absorption of the study

- No other condition which, in the opinion of the investigator, would preclude
participation in this trial.
We found this trial at
225 Summit Avenue
Montvale, New Jersey 07645
Phone: 646-422-4632
Montvale, NJ
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136 Mountainview Boulevard
Basking Ridge, New Jersey 07920
Phone: 646-422-4632
Basking Ridge, NJ
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Commack, New York 11725
Phone: 646-422-4632
Commack, NY
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Harrison, New York
Phone: 646-422-4632
Harrison, NY
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1275 York Ave
New York, New York 10021
(212) 639-2000
Phone: 646-422-4632
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
New York, NY
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