Improving Peptide Receptor Radionuclide Therapy with PARP inhibitors.
- Conditions
- well-differentiated advanced gastroenteropancreatic neuro-endocrine tumors.
- Registration Number
- NL-OMON21221
- Lead Sponsor
- Erasmus MC, Rotterdam, the Netherland
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
Histologically proven locally advanced or metastatic, well-differentiated 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
-Two cycles of PRRT are considered by the treating physician
-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
-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 To determine the maximum tolerated dose (MTD) of olaparib in combination with PRRT in patients with a well-differentiated advanced NET, progressive after treatment with PRRT.
- Secondary Outcome Measures
Name Time Method To evaluate the efficacy, pharmacokinetics (PK) and biomarker response of olaparib in<br>combination with PRRT in patients with a well-differentiated advanced NET, progressive after treatment with PRRT.