Combining olaparib with PRRT for advanced gastroenteropancreatic neuroendocrine tumors

Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

This trial will test whether giving the oral PARP blocker olaparib together with PRRT helps adults with advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors that progressed after prior PRRT.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Erasmus Medical Center (other)
• Drugs / interventions: sunitinib, chemotherapy, radiation
• Locations: 1 site (Rotterdam, South Holland)
• Trial ID: NCT05870423 on ClinicalTrials.gov

What this trial studies

This is a phase 1 dose-escalation trial designed to find the maximum tolerated dose of olaparib when given alongside salvage 177Lu‑DOTATATE PRRT. Eligible participants have well-differentiated (grade 1–3) gastroenteropancreatic NETs with progression after prior PRRT, measurable disease, and confirmed somatostatin receptor uptake. Secondary aims include preliminary measures of tumor response, pharmacokinetics of olaparib, and biomarker changes. Treatment and follow-up are conducted at Erasmus MC in Rotterdam.

Who should consider this trial

Good fit: Adults (≥18) with well-differentiated (grade 1–3) gastroenteropancreatic NETs that progressed after prior PRRT, measurable somatostatin receptor–positive disease, KPS >60, and adequate blood counts and renal and liver function are typical candidates.

Not a fit: Patients with poor bone marrow reserve, significant renal impairment (creatinine clearance <50 mL/min), absent somatostatin receptor uptake on PET, or low performance status are unlikely to benefit or may be ineligible.

Why it matters

Potential benefit: If successful, the combination could increase tumor control from PRRT without raising the radiation dose, potentially improving response rates and delaying progression.

How similar studies have performed: Preclinical models show PARP inhibitors can sensitize tumors to PRRT and PARP inhibitors are effective in other cancers, but clinical data combining PARP blockade with PRRT are limited and this approach remains early-stage.

Eligibility criteria

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:

* 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.

Where this trial is running

Rotterdam, South Holland

• Erasmus MC — Rotterdam, South Holland, Netherlands (RECRUITING)

Study contacts

• Study coordinator: M.N. Becx

Conditions: Neuroendocrine Tumors, Peptide Receptor Radionuclide Therapy