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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05053854
Recruitment Status : Recruiting
First Posted : September 23, 2021
Last Update Posted : August 24, 2022
Sponsor:
Information provided by (Responsible Party):
Peter MacCallum Cancer Centre, Australia

Study Description
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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).

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Drug: Talazoparib Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective single arm, single centre, Phase 1 study
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 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
Other Name: Combination product: 177Lu-DOTA-Octreotate


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 midgut origin.
  4. Must have progressed on at least one line of prior therapy, which can include somatostatin analogues
  5. Progressive disease on imaging (CT/MRI or GaTate PET/CT), or evidence of uncontrolled hormone-secretory symptoms despite conventional treatment
  6. Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
  7. No discordant FDG-avid disease on 18F-FDG PET/CT
  8. No evidence of significant uncorrected carcinoid heart disease
  9. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments

  10. 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).
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Grace Kong 85595000 NMResearch@petermac.org
Contact: Research Manager 8559 6602

Locations
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Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Contact: MC Research Manager    +61385596602    NMResearch@petermac.org   
Sponsors and Collaborators
Peter MacCallum Cancer Centre, Australia
More Information
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Responsible Party: Peter MacCallum Cancer Centre, Australia
ClinicalTrials.gov Identifier: NCT05053854    
Other Study ID Numbers: PMC67199
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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peter MacCallum Cancer Centre, Australia:
NET
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
 Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents