We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Tracking Information
First Submitted Date  ICMJE September 2, 2021
First Posted Date  ICMJE September 23, 2021
Last Update Posted Date August 24, 2022
Actual Study Start Date  ICMJE December 8, 2021
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2021)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2021)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours
Official Title  ICMJE Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE Neuroendocrine Tumors
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Talazoparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 20, 2021)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2025
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Grace Kong 85595000 NMResearch@petermac.org
Contact: Research Manager 8559 6602
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05053854
Other Study ID Numbers  ICMJE PMC67199
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Peter MacCallum Cancer Centre, Australia
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Peter MacCallum Cancer Centre, Australia
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Peter MacCallum Cancer Centre, Australia
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP