Improving peptide receptor radionuclide therapy with poly ADP ribose polymerase inhibitor.

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

- Histologically proven locally advanced or metastatic, well-differentiated
(grade 1, 2 or 3) NET
- Disease progression based on RECIST v1.1 following initial or salvage
treatment with PRRT with 177Lu-DOTATATE with a progression free interval of at
least 12 months since first cycle of previous administration of PRRT or with no
suitable systemic alternative treatment options
- The patient is eligible for two cycles of salvage PRRT
- Measurable disease according to RECIST v1.1 on CT/MRI
- Confirmed presence of somatostatin receptors on all target lesions on CT/MRI,
based on positive uptake on a 68Ga-DOTATATE/-TOC/-NOC PET-CT/MRI scan
- Age >= 18 years
- Karnofsky Performance Score (KPS) > 60

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Hb concentration <6.2 mmol/L; white blood cell count <3x109/L; platelets
<100x109/L; neutrophil count <1.5x109/L
- Renal insufficiency defined as a creatinine clearance <50 mL/min, measured in
24-hour urine collection
- Liver function or enzyme abnormalities defined as a total bilirubin >3 x ULN,
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN
or serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
- Pregnancy, lactation and inability to comply with effective means of
contraception in females of child-bearing age.
- Neuroendocrine carcinoma of any origin.
- Any surgery, radioembolization, chemoembolization, chemotherapy and
radiofrequency ablation within 12 weeks prior to inclusion in the study.
Interferons, everolimus, sunitinib or other systemic therapies within 4 weeks
prior to inclusion in the study.
- Uncontrolled congestive heart failure (NYHA II, III, IV).
- Patients with any other significant medical, psychiatric, or surgical
condition, currently uncontrolled by treatment, which may interfere with the
completion of the study.
- Prior external beam radiation therapy to more than 25% of the bone marrow.
- Other known co-existing malignancies except non-melanoma skin cancer and
carcinoma in situ of the uterine cervix, unless definitively treated and proven
no evidence of recurrence for 5 years.
- Patients who use a strong CYP3A4 inhibitor within 1 week before start of the
treatment or a CYP3A4 inducer within 4 weeks before start of the treatment.
- History or evidence of any other clinically significant disorder, condition
or disease (with the exception of those outlined above) that, in the opinion of
the investigator would pose a risk to subject safety or interfere with the
study evaluation, procedures or completion.
- Known allergy or intolerance for the (non-)investigational drugs
- Inability to provide informed consent
- End of life care

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To determine the maximum tolerated dose (MTD) of olaparib in combination with<br /><br>PRRT in patients with a well-differentiated advanced NET, progressive after<br /><br>treatment with PRRT.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To evaluate the efficacy, pharmacokinetics (PK) and biomarker response of<br /><br>olaparib in<br /><br>combination with PRRT in patients with a well-differentiated advanced NET,<br /><br>progressive after treatment with PRRT.</p><br>