Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

NCT05870423 | Recruiting Phase 1

• 1 other identifier: NL79259.078.21
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroendocrine Tumors; Peptide Receptor Radionuclide Therapy

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Incidence and severity of adverse events according to CTCAE v5.0

  3 years

• Maximum tolerated dase

  Determination of the MTD of olaparib in combination with standard dose PRRT

  3 years

Secondary Outcomes (3)

• Survival rates

  3 years

• Best response

  3 years

• Antitumor effects

  3 years

Study Arms (4)

PRRT + olaparib 100mg q.d.

EXPERIMENTAL

administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 100mg q.d.

Drug: olaparib

PRRT + olaparib 100mg b.i.d.

EXPERIMENTAL

administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 100mg b.i.d.

Drug: olaparib

PRRT + olaparib 200mg b.i.d.

EXPERIMENTAL

administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 200mg b.i.d.

Drug: olaparib

PRRT + olaparib 300mg b.i.d.

EXPERIMENTAL

administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 300mg b.i.d.

Drug: olaparib

Interventions

olaparib DRUG

18 days olaparib during each cycle of PRRT

Also known as: Lynparza

PRRT + olaparib 100mg b.i.d.; PRRT + olaparib 100mg q.d.; PRRT + olaparib 200mg b.i.d.; PRRT + olaparib 300mg b.i.d.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3000CA, Netherlands

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Central Study Contacts

M.N. Becx

CONTACT

43449; m.becx@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: coordinating investigator

Model Details: 3+3 dose-escalation.

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: May 23, 2023
• Study Start: June 1, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: June 5, 2025

Record last verified: 2025-05

Locations

NL (1)