PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours (PARLuNET)
Primary Purpose
Neuroendocrine Tumors
Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Talazoparib
Sponsored by
About this trial
This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring NET
Eligibility Criteria
Inclusion Criteria:
- 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 midgut origin.
- Must have progressed on at least one line of prior therapy, which can include somatostatin analogues
- Progressive disease on imaging (CT/MRI or GaTate PET/CT), or evidence of uncontrolled hormone-secretory symptoms despite conventional treatment
- Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
- No discordant FDG-avid disease on 18F-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.
- Albumin ≥ 30 g/L
- Adequate renal function: eGFR ≥ 60 ml/min
Exclusion Criteria:
- 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).
Sites / Locations
- Peter MacCallum Cancer CentreRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
177Lu-DOTA-Octreotate + talazoparib
Arm Description
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.
Outcomes
Primary Outcome Measures
Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate
Dose limiting toxicity talazoparib
The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.
Secondary Outcome Measures
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
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.
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.
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.
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
Full Information
NCT ID
NCT05053854
First Posted
September 2, 2021
Last Updated
August 21, 2022
Sponsor
Peter MacCallum Cancer Centre, Australia
1. Study Identification
Unique Protocol Identification Number
NCT05053854
Brief Title
PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peter MacCallum Cancer Centre, Australia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors
Keywords
NET
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Prospective single arm, single centre, Phase 1 study
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
177Lu-DOTA-Octreotate + talazoparib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Talazoparib
Other Intervention Name(s)
Combination product: 177Lu-DOTA-Octreotate
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
Description
Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate
Time Frame
Through study completion, up to 18 months following first administration of PRRT.
Title
Dose limiting toxicity talazoparib
Description
The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.
Time Frame
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 Measure Information:
Title
Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Description
Safety of the combination will be measured by AEs and SAEs
Time Frame
Through Study completion, up to 18 months after the last patient commences treatment.
Title
Radiographic progression free survival
Description
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.
Time Frame
Through study completion, up to 18 months following first administration of PRRT.
Title
Overall Survival
Description
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.
Time Frame
Through study completion, up to 18 months following first administration of PRRT.
Title
Treatment discontinuation due to toxicity
Description
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.
Time Frame
Through study completion, up to 18 months following first administration of PRRT.
Title
Rate of Treatment discontinuation due to toxicity
Description
The percentage of patients who discontinue treatment due to treatment related toxicity will be reported and will be also categorised by dose level
Time Frame
Through study completion, up to 18 months following first administration of PRRT.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 midgut origin.
Must have progressed on at least one line of prior therapy, which can include somatostatin analogues
Progressive disease on imaging (CT/MRI or GaTate PET/CT), or evidence of uncontrolled hormone-secretory symptoms despite conventional treatment
Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
No discordant FDG-avid disease on 18F-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.
Albumin ≥ 30 g/L
Adequate renal function: eGFR ≥ 60 ml/min
Exclusion Criteria:
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Grace Kong
Phone
85595000
Email
NMResearch@petermac.org
First Name & Middle Initial & Last Name or Official Title & Degree
Research Manager
Phone
8559 6602
Facility Information:
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MC Research Manager
Phone
+61385596602
Email
NMResearch@petermac.org
12. IPD Sharing Statement
Plan to Share IPD
No
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PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours
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