PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours (PARLuNET)
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|ClinicalTrials.gov Identifier: NCT05053854|
Recruitment Status : Recruiting
First Posted : September 23, 2021
Last Update Posted : August 24, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Neuroendocrine Tumors||Drug: Talazoparib||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Prospective single arm, single centre, Phase 1 study|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor|
|Actual Study Start Date :||December 8, 2021|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||December 31, 2025|
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.
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
Other Name: Combination product: 177Lu-DOTA-Octreotate
- Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate [ Time Frame: Through study completion, up to 18 months following first administration of PRRT. ]Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate
- Dose limiting toxicity talazoparib [ 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) ]The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.
- Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: Through Study completion, up to 18 months after the last patient commences treatment. ]Safety of the combination will be measured by AEs and SAEs
- Radiographic progression free survival [ Time Frame: Through study completion, up to 18 months following first administration of PRRT. ]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 [ Time Frame: Through study completion, up to 18 months following first administration of PRRT. ]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 [ Time Frame: Through study completion, up to 18 months following first administration of PRRT. ]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 [ Time Frame: Through study completion, up to 18 months following first administration of PRRT. ]The percentage of patients who discontinue treatment due to treatment related toxicity will be reported and will be also categorised by dose level
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05053854
|Contact: Grace Kong||85595000||NMResearch@petermac.org|
|Contact: Research Manager||8559 6602|
|Peter MacCallum Cancer Centre||Recruiting|
|Melbourne, Victoria, Australia, 3000|
|Contact: MC Research Manager +61385596602 NMResearch@petermac.org|
|Responsible Party:||Peter MacCallum Cancer Centre, Australia|
|Other Study ID Numbers:||
|First Posted:||September 23, 2021 Key Record Dates|
|Last Update Posted:||August 24, 2022|
|Last Verified:||August 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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