A Randomized Clinical Trial Investigating Olaparib, Durvalumab (MEDI4736) and UV1 as Maintenance Therapy in BRCAwt Patients with Recurrent Ovarian Cancer

Phase 2

Conditions: cancer of the ovary that has recurred
recurrent ovarian cancer
10038594

Registration Number: NL-OMON53750

Lead Sponsor: ordic Society of Gynaecological Oncology - Clinical Trial Unit, Department of Oncology, 9431, Rigshospitalet, Copenhagen University Hospital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
the protocol.
2. Histologically diagnosed epithelial ovarian, fallopian tube or primary
peritoneal cancer.
3. Radiological or histological confirmation of relapse disease >= 6 month after
last chemotherapy
4. Patients who are non-gBRCAmut or tBRCAwt
5. Have completed at least two lines, but no more than 4 lines, of
platinum-containing chemotherapy, which means that patients at first, second or
third relapse with treatment free interval of more than 6 months are eligible.
a. Subjects must have completed at least 4 cycles of the last
platinum-containing chemotherapy
6. Be either:
a. PARPi naive
b. Earlier treated with PARPi and not progressed during 6 months of PARPi
therapy
7. Must have, in the opinion of the investigator, CR or PR on the
post-treatment scan and no evidence of rising CA-125 level, following
completion of the last chemotherapy course.
8. Patient consents to Myriad myChoice HRD test.
9. Must be included in the study within 10 weeks of completion of the final
dose of platinum-containing chemotherapy.
10. Age >=18 years
11. Body weight > 30 kg
12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
13. Must have a life expectancy >= 16 weeks.
14. Must have normal organ and bone marrow function measured within 28 days
prior to administration of study treatment as defined below:
- Haemoglobin >= 10.0 g/dL (6,2 mmol/L) with no blood transfusion in the past 28
days
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Total bilirubin <= 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase
(SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase
(SGPT)) <= 2.5 x institutional upper limit of normal unless liver metastases are
present in which case, they must be <= 5x ULN
- Must have creatinine clearance estimated of >= 51 mL/min using the
Cockcroft-Gault equation or based on a urine test.
15. Ability to swallow oral medications (tablets) without chewing, breaking,
crushing, opening or otherwise altering the product formulation.
16. Post-menopausal or evidence of non-childbearing status for women of
childbearing potential: negative urine or serum pregnancy test within 28 days
of study treatment and confirmed prior to treatment on day 1.

Exclusion Criteria

1. Previous immunotherapy (for example anti-PD-1/L1, including durvalumab).
2. Other malignancy unless curatively treated with no evidence of disease for >=
5 years except adequately treated non-melanoma skin cancer, curatively treated
in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1
endometrial carcinoma.
3. Resting ECG indicating uncontrolled, potentially reversible cardiac
conditions, as judged by the investigator (e.g., unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF
prolongation > 500 ms, electrolyte disturbances, etc.), or patients with
congenital long QT syndrome.
4. Patients with myelodysplastic syndrome/acute myeloid leukemia or with
features suggestive of MDS/AML.
5. Patients with symptomatic uncontrolled brain metastases. A scan to confirm
the absence of brain metastases is not required. The patient can receive a
stable dose of corticosteroids before and during the study if these were
started at least 4 weeks prior to treatment. Patients with spinal cord
compression unless considered to have received definitive treatment for this
and evidence of clinically stable disease for 28 days.
6. Patients considered a poor medical risk due to a serious, uncontrolled
medical disorder, non-malignant systemic disease or active, uncontrolled
infection. Examples include, but are not limited to, uncontrolled ventricular
arrhythmia, recent (within 3 months) myocardial infarction, 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.
7. Disease progression during or within 4 weeks after PARPi therapy.
8. Subject have received > 2 series of chemotherapy for relapse
9. Concomitant treatment with bevacizumab within the last 3 weeks.
10. Concomitant therapy with any other anticancer therapy or chronic use of
systemic corticosteroids of more than 10mg prednisolone daily.
11. 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 starting study
treatment is 2 weeks.
12. 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 study treatment is 5 weeks for
enzalutamide or phenobarbital and 3 weeks for other agents
13. Previous allogeneic bone marrow transplant or double umbilical cord blood
transplantation
14. Subjects being considered at poor medical condition due to a serious,
uncontrolled medical disorder or non-malignant systemic disease.
15. Major surgery or significant traumatic injury within 28 days of run-in
16. Immunocompromised patients, e.g., patients who are known to be
serologically positive for human immunodeficiency virus (HIV), patients with
active hepatitis B (defined

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Progression-free survival (PFS) arm A versus C</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Key secondary endpoints:<br />• PFS arm B versus arm C<br />• Assessment of PROs<br /><br />Other secondary endpoints:<br />• PFS assessed by blinded independent central review (BICR)<br />• Efficacy according to stratification factors<br />• Efficacy according to PD-L1 status<br />• Overall survival (OS)<br />• Time to first subsequent therapy (TFST)<br />• Subsequent progression (PFS2)<br />• Time to second subsequent therapy (TSST)<br />• Objective Response Rate (ORR)<br />• Disease Control Rate (DCR)<br />• Safety analysis<br /><br />Exploratory/translational research:<br />• Evaluation of changes in genetic, molecular and immunological markers of<br />response and/or resistance over time.<br />• Correlation between changes in genetic, molecular and immunological markers<br />and efficacy in defined subgroups.</p>