PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase 1 dose-escalation study is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate peptide receptor radionuclide therapy (PRRT) in patients with metastatic pancreatic neuroendocrine tumour (NET).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peter MacCallum Cancer Centre, Australia
• Treatments: Talazoparib

Criteria

Inclusion Criteria:

1. Patient must be > or equal to18 years of age and must have provided written informed consent.

2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

3. Histologically confirmed Grade 2 NET, Ki-67 of 3-20%, from pancreatic origin, biopsy performed within 6 months without intervening change of treatment

4. Must have progressed on one line of prior therapy, which can include somatostatin analogues

5. Progressive disease on imaging (CT/MRI or GaTate PET/CT), or evidence of uncontrolled hormone-secretory symptoms despite conventional treatment

6. Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score

7. No discordant FDG-avid disease on 18F-FDG PET/CT

8. No evidence of significant uncorrected carcinoid heart disease

9. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments

10. Patients must have adequate bone marrow, hepatic and renal function documented within 14 days prior to registration, defined as:

• Haemoglobin ≥100 g/L

• Absolute neutrophil count ≥1.5x109/L

• Platelets ≥150 x109/L

• Total bilirubin ≤1.5 x upper limit of normal (ULN)

• Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT)

≤2.5 x ULN if there is no evidence of liver metastasis or ≤5 x ULN in the presence of liver metastases.

• Albumin ≥ 30 g/L

• Adequate renal function: eGFR ≥ 60 ml/min

Exclusion Criteria:

1. Surgery or radiotherapy within <3 weeks of registration. Patients must have recovered from any effects of any major surgery.

2. Any prior exposure to peptide receptor radionuclide therapy (177Lu, 111In or 90Y labelled), PARPi, immunotherapy

3. Uncontrolled intercurrent illness that is likely to impede participation and /or compliance

4. Other malignancies unless curatively treated with no evidence of disease within previous 3-years other than adequately treated non-melanoma skin cancer or melanoma in situ.

5. Previous or current history of myelodysplastic syndrome/acute myeloid leukemia

6. Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication.

7. Use of strong P-gp inhibitors (eg, dronedarone, quinidine, ranolazine, verapamil, ketoconazole, itraconazole), P-gp inducers (eg, rifampin, tipranavir/ritonavir), or BCRP inhibitors (eg, elacridar [GF120918]) should be avoided.

8. Participation in another clinical study with an investigational product or another systemic therapy administered in the last 3 weeks (except short acting SSA).