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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05053854




Registration number
NCT05053854
Ethics application status
Date submitted
2/09/2021
Date registered
23/09/2021
Date last updated
26/10/2023

Titles & IDs
Public title
PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours
Scientific title
Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor
Secondary ID [1] 0 0
PMC67199
Universal Trial Number (UTN)
Trial acronym
PARLuNET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroendocrine Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Talazoparib

Experimental: 177Lu-DOTA-Octreotate + talazoparib - 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.


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
Timepoint [1] 0 0
Through study completion, up to 18 months following first administration of PRRT.
Primary outcome [2] 0 0
Dose limiting toxicity talazoparib
Timepoint [2] 0 0
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 outcome [1] 0 0
Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Timepoint [1] 0 0
Through Study completion, up to 18 months after the last patient commences treatment.
Secondary outcome [2] 0 0
Radiographic progression free survival
Timepoint [2] 0 0
Through study completion, up to 18 months following first administration of PRRT.
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
Through study completion, up to 18 months following first administration of PRRT.
Secondary outcome [4] 0 0
Treatment discontinuation due to toxicity
Timepoint [4] 0 0
Through study completion, up to 18 months following first administration of PRRT.
Secondary outcome [5] 0 0
Rate of Treatment discontinuation due to toxicity
Timepoint [5] 0 0
Through study completion, up to 18 months following first administration of PRRT.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05053854
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Grace Kong
Address 0 0
Country 0 0
Phone 0 0
85595000
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05053854