Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed). (LUPARPED)

April 9, 2026 updated by: Fundación de investigación HM

Single-arm Open-label Phase I/II Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).

Study in children and adolescents of 177Lu DOTATATE (Lutathera®) combined with the PARP inhibitor olaparib for treatment of recurrent or relapsed solid tumours expressing somatostatin receptors (SSTR) (LuPARPed)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Relapsed/refractory (R/R) solid tumours at the paediatric age have a dismal prognosis [5-year overall survival (OS) less than 20%. There is growing evidence about the somatostatin receptor (SSTR) expression in paediatric tumours, which opens a new diagnostic and therapeutic tool. Somatostatin receptor-targeted therapy with 177Lu-DOTA0-Tyr3-octreotate (177[Lu]Lu DOTA-TATE, 177Lu-DOTATATE, Lutathera®) has been approved by the EMA (2017) and the FDA (2018) for the treatment of adults with midgut neuroendocrine tumours after the excellent results achieved in the phase III NETTER-1 study.

177Lu-DOTATATE is already being explored as monotherapy in children with R/R high-risk neuroblastoma, CNS tumours or meningiomas in 2 pilot studies and 4 clinical trials (ISRCTN98918118, NCT04903899, NCT03966651, NCT05278208). There are two on going clinical trials exploring the recommended phase 2 dose (RP2D) of 177Lu-DOTATATE in children younger than12 years old, but results are still pending.

The results show promising but insufficient results. Because of its beta particle emission, 177Lu-DOTATATE mainly produces DNA single-strand breaks (SSBs) that are easily repaired by the organism. In order to enhance its effect, the investigators propose its combination with PARP inhibitors (iPARP) so that the SSBs could not be repaired and would lead to the formation of DNA double strand breaks (DSBs) and, subsequently, to cell death. This combination is already being explored in different clinical trials in adults with neuroendocrine tumours and prostate cancer. An interesting study analysed the perfect scheme for the 177Lu-DOTATATE and olaparib combination and concluded that olaparib should be delayed 24 hours after 177Lu-DOTATATE administration in order to facilitate normal tissue repair without decreasing antitumoural activity. It also concludes that there is no benefit in continuing olaparib after 4 weeks of continuous treatment. Olaparib has also been administered in children and there is today a recommended phase 2 dose (187.5 mg/m2 BID).

The 177LUDOTATATE and olaparib combination is already being explored in different clinical trials in adults with neuroendocrine tumors and prostate cancer 19-21. One of these studies (NCT04375267) has already published results, showing that, when combined with 177LUDOTATATE, olaparib recommended starting dose is 200 mg BID instead of the normal 300 mg BID dose.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
    • Madrid
      • Boadilla del Monte, Madrid, Spain, 28660

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • 18 months - 18 years of age at the time of the initial diagnosis.
  • ≥ 3 years at the moment of inclusion in the trial.
  • Diagnosis: relapsed/refractory solid tumours with positive uptake on SSTR-PET (PET-CT or PET-MRI), performed in the previous three months before entering the study.

The evaluation of SSTR expression will be classified according to a qualitative 4-point scale: SSTR expression V (visual score):

  • Score = 0: Below or equal to blood pool
  • Score = 1: Above blood pool and lower than liver
  • Score = 2: Equal to or above liver and lower than spleen
  • Score = 3: Equal to or above spleen

Patients with scores ≥ 2 in the majority of the tumoral lesions will be considered to have a positive SSTR-PET and will be therefore eligible for the trial. Patients with a higher score are presumed to have a better response to the treatment.

It is admissible to have non-measurable disease only (e.g., HR-NB with bone-only or bone-marrow-only active disease).

  • Performance status ≥ 50% according to Lansky scale (<16 years old) or Karnofsky scale (for ≥16 years old).
  • Life expectancy of at least 3 months.
  • Availability of ability to swallow tablets or capsules.

  • Adequate organ function within 28 days prior to enrolment, as defined by:

    • Hb ≥10 g/dl (packed red blood transfusion is acceptable up to 24 hours prior starting treatment);
    • White blood cell (WBC) count ≥ 2500/μL (equivalent to 2.5 x 109/L)
    • Absolute Neutrophil Count (ANC) ≥ 1000/μl;
    • Platelets ≥ 100.000/μl, without transfusion in the prior ≥7 days;
    • Serum plasma creatinine ≤ 1.5 x upper limit of normal (ULN) OR estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 (assessed by 2009-Schwartz formula).
    • Total bilirubin ≤ 1.5 x the institutional ULN. For patients with known Gilbert's Syndrome ≤ 3.0 ULN is permitted.
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 ULN.
    • Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L)
  • A negative serum or urine pregnancy test in women with onset of menses or ≥12 years of age.
  • Patients of reproductive potential must agree to use highly effective contraceptive methods for the entire study duration and up to 7 months, in case of females, and 4 months in case of males, after the last dose of Lutathera, or up to 6 months, in case of females, and 3 months in case of males, after the last dose of olaparib, whichever takes places later.
  • Have the ability to comprehend and willingness to provide written informed consent (ICF) for the study before patient registration or any trial-related screening procedures. If the patient is <18 years old, the written informed consent must be signed by the parent(s) or legal guardian(s) according to national regulations. In the case of patients between 12 and 17 years, they must sign an assent form, and if the patient turns 18 during their participation in the study, they must sign an informed consent form.
  • Adequate recovery from major surgery prior to receiving study treatment.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Exclusion criteria

  • Previous significant drug-induced hepatitis toxicity experienced in the past that has required treatment dose reductions, treatment discontinuation or that, at the investigator discretion, could infer a risk.
  • Having received more than one previous treatment with other radiolabelled somatostatin analogues.
  • Inability to swallow tablets or capsules.
  • Subjects who are currently receiving any other anticancer and/or investigational agents (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]). There must be at least 28 days of washout from any prior treatment. In case of checkpoints inhibitors, there should be at least 4 months of washout. Palliative Radiation Therapy for symptom control (e.g. pain relief) could be acceptable, at the discretion of the investigator.
  • Treatment with long-acting somatostatin analogues within 28 days prior the administration of 177Lu-DOTATATE.
  • Known hypersensitivity to any of the excipients.
  • Subjects who have an uncontrolled infection.
  • Lactating women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lu-DOTATATE (Lutathera® ) and olaparib

Lu-DOTATATE (Lutathera®) and olaparib for a maximum of 4 cycles unless unacceptable toxic effects occur, there is centrally confirmed disease progression (according to RECIST v1.1/RAPNO/INRC) on imaging, the patient is unable or unwilling to adhere to trial procedures, the patient withdraws consent, or the patient dies.

177Lu-DOTATATE will be administered intravenously, on day 1, every 8 weeks, at a fixed dose of 200 mCi (7.4 GBq) for children >= 12 years old infused intravenously over a period of 30 minutes. For children younger than 12 years old, the dose that will be administered is 200 MBq per kilogram of body weight (maximum 7.4 GBq) infused intravenously over a period of 30 minutes.

Olaparib will be administered PO, BID, days 3-28, every 8 weeks. Dose escalation of olaparib with the classic 3+3 design: DL1 62.5 mg/m2 (max 100 mg); DL2 93.5 mg/m2 (max 150 mg); DL3 125 mg/m2 (max 200 mg).
Drug: Olaparib; 177Lu-DOTATATE
7Lu-DOTATATE will be administered intravenously, on day 1, every 8 weeks, at a fixed dose of 200 mCi (7.4 GBq) for children >= 12 years old infused intravenously over a period of 30 minutes. For children younger than 12 years old, the dose that will be administered is 200 MBq per kilogram of body weight (maximum 7.4 GBq) infused intravenously over a period of 30 minutes. Concomitant to 177Lu-DOTATATE, patients will receive IV fluids and an IV infusion of amino acid solution for renal protection23. Patients will receive four infusions every 8 weeks (maximum cumulative radioactivity, 29.6 GBq [800 mCi]). Olaparib will be administered PO, BID, days 2-29, every 8 weeks at a fixed dose of 187.5mg/m2 twice daily (BID).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To estimate the safety of the combination of 177LUDOTATATE and olaparib.
Time Frame: Through first cycle, an average of 8 weeks
Measured by incidence of DLTs; finding of MTD and RP2D
Through first cycle, an average of 8 weeks
To estimate the preliminary activity of the combination of 177LUDOTATATE and olaparib.
Time Frame: From enrollment to the end of treatment, up to 24 months
ORR
From enrollment to the end of treatment, up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To test the activity of the combination of 177LUDOTATATE and olaparib
Time Frame: Through study completion, up to 24 months
DCR, DOR, TTR, PFS, OS, quality of life assessment
Through study completion, up to 24 months
To test the safety of the combination of 177LUDOTATATE and olaparib
Time Frame: Through study completion, up to 24 months
AEs, SAEs
Through study completion, up to 24 months
To test the tolerability of the combination of 177LUDOTATATE and olaparib
Time Frame: Through study completion, up to 24 months
Frequency of treatment reductions, need of drug holidays and delays on treatment administration
Through study completion, up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación de investigación HM

Investigators

  • Study Director: Marta Osuna Marco, PhD, HM Monteprincipe

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2024

Primary Completion (Estimated)

July 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

September 4, 2024

First Submitted That Met QC Criteria

September 18, 2024

First Posted (Actual)

September 23, 2024

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LuPARPed-HM-2024
  • 2024-512613-40-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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