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

NCT05053854 | Recruiting Phase 1

• 1 other identifier: PMC67199
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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 or midgut neuroendocrine tumour (NET).

Conditions

Neuroendocrine Tumors

Keywords

NET

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate

  Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate

  Through study completion, up to 18 months following first administration of PRRT.

• Dose limiting toxicity talazoparib

  The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.

  Each cohort of 3 patients be assessed for DLTs in the first 6 weeks (cycle 2) of treatment and a dose for the next cohort will be determined (each cycle is 8 weeks)

Secondary Outcomes (5)

• Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  Through Study completion, up to 18 months after the last patient commences treatment.

• Radiographic progression free survival

  Through study completion, up to 18 months following first administration of PRRT.

• Overall Survival

  Through study completion, up to 18 months following first administration of PRRT.

• Treatment discontinuation due to toxicity

  Through study completion, up to 18 months following first administration of PRRT.

• Rate of Treatment discontinuation due to toxicity

  Through study completion, up to 18 months following first administration of PRRT.

Study Arms (1)

177Lu-DOTA-Octreotate + talazoparib

EXPERIMENTAL

Patients will receive 4 cycles of 177Lu-DOTA-Octreotate every 8 weeks, the last 3 cycles combined with talazoparib on days 2-6 of each cycle.

Drug: Talazoparib

Interventions

Talazoparib DRUG

During dose escalation, doses of talazoparib that can be administered are 0.1mg, 0.25mg, 0.5mg or 1mg oral daily. Talazoparib will be given on days 2-6 of each cycle of 177Lu-DOTA-Octreotate for cycles 2-4, every 8 weeks

Also known as: Combination product: 177Lu-DOTA-Octreotate

177Lu-DOTA-Octreotate + talazoparib

Eligibility Criteria

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

You may qualify if:

• Patient must be \> or equal to18 years of age and must have provided written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Histologically confirmed Grade 2 NET, Ki-67 of 3-20%, from pancreatic or intestinal origin.
• Patient clinically suitable for PRRT
• Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
• No discordant FDG-avid disease on FDG PET/CT
• No evidence of significant uncorrected carcinoid heart disease
• Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments
• Patients must have adequate bone marrow, hepatic and renal function 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.

You may not qualify if:

• Surgery or radiotherapy within \<3 weeks of registration. Patients must have recovered from any effects of any major surgery.
• Any prior exposure to peptide receptor radionuclide therapy (177Lu, 111In or 90Y labelled), PARPi, immunotherapy
• Uncontrolled intercurrent illness that is likely to impede participation and /or compliance
• 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.
• Previous or current history of myelodysplastic syndrome/acute myeloid leukemia
• Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication.
• 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.
• Participation in another clinical study with an investigational product or another systemic therapy administered in the last 3 weeks (except short acting SSA).

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

talazoparib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Grace Kong

CONTACT

85595000; NMResearch@petermac.org

Research Manager

CONTACT

8559 6602

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective single arm, single centre, Phase 1 study

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 23, 2021
• Study Start: December 8, 2021
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)