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

Neuroendocrine Tumors Clinical Trial

— PARLuNET  

Official title:

Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05053854
• Other study ID #: PMC67199
• Status: Recruiting
• Phase: Phase 1
• Start date: December 8, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Peter MacCallum Cancer Centre, Australia
• Contact: Grace Kong
• Phone: 85595000
• Email: NMResearch[@]petermac.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This phase 1, single arm, single centre study is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate in patients with metastatic NET. Patients will receive 1 cycle of 177Lu-DOTA-Octreotate alone followed by 3 cycles of 177Lu-DOTA-Octreotate combined with 5 days of talazoparib.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 or intestinal origin.

4. Patient clinically suitable for PRRT

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

6. No discordant FDG-avid disease on FDG PET/CT

7. No evidence of significant uncorrected carcinoid heart disease

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

9. 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.
• 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).

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

Drug:
• Talazoparib
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

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Peter MacCallum Cancer Centre, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	Safety of the combination will be measured by AEs and SAEs	Through Study completion, up to 18 months after the last patient commences treatment.
Secondary	Radiographic progression free survival	The time from treatment initiation to the first date of progression on imaging or death due to any cause. Imaging progression will be assessed by RECIST 1.1. Patients who commence new systemic therapy before evidence of disease progression on conventional imaging will be considered to have progressed.	Through study completion, up to 18 months following first administration of PRRT.
Secondary	Overall Survival	The time from treatment initiation to the date of death due to any cause. For patients alive, the time will be censored at the last time the patients was known to be alive.	Through study completion, up to 18 months following first administration of PRRT.
Secondary	Treatment discontinuation due to toxicity	The number of patients who discontinue treatment at any time due to treatment related toxicity will be reported and will be also categorised by dose level.	Through study completion, up to 18 months following first administration of PRRT.
Secondary	Rate of Treatment discontinuation due to toxicity	The percentage of patients who discontinue treatment due to treatment related toxicity will be reported and will be also categorised by dose level	Through study completion, up to 18 months following first administration of PRRT.