RecruitingPhase 1NCT05870423

Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

Sponsor

Erasmus Medical Center

Enrollment

24 participants

Start Date

Jun 1, 2022

Study Type

INTERVENTIONAL

Conditions

Neuroendocrine Tumors Peptide Receptor Radionuclide Therapy

Summary

This is a phase 1 dose-escalation study to determine the maximum tolerated dose of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced gastroenteropancreatic NET (GEP NET), progressive after PRRT. As secondary objectives, efficacy, pharmacokinetics and biomarker response will be investigated.

Eligibility

Min Age: 18 Years

Inclusion Criteria7

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 Criteria15

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.