Combining Lutathera® and Olaparib for treating recurrent solid tumors in children and adolescents

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).

This study is testing if combining Lutathera® with olaparib can help children and teenagers with hard-to-treat solid tumors that have certain receptors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 3 Years and up
• Sex: All
• Sponsor: Fundación de investigación HM (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation
• Locations: 1 site (Boadilla del Monte, Madrid)
• Trial ID: NCT06607692 on ClinicalTrials.gov

What this trial studies

This study investigates the use of 177Lu-DOTATATE (Lutathera®) in combination with the PARP inhibitor olaparib for children and adolescents with recurrent or relapsed solid tumors that express somatostatin receptors. The approach aims to enhance the effectiveness of 177Lu-DOTATATE, which primarily causes single-strand DNA breaks, by preventing the repair of these breaks through the use of olaparib, leading to more lethal double-strand breaks. Eligible patients will undergo SSTR-PET imaging to confirm the presence of somatostatin receptors before treatment. The study is designed to assess the safety and efficacy of this combination therapy in a pediatric population with poor prognosis solid tumors.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents aged 18 months to 18 years with relapsed or refractory solid tumors that show positive uptake on SSTR-PET imaging.

Not a fit: Patients with solid tumors that do not express somatostatin receptors or those who are not within the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for children and adolescents with difficult-to-treat solid tumors.

How similar studies have performed: While there have been pilot studies exploring 177Lu-DOTATATE in pediatric populations, the combination with PARP inhibitors like olaparib is a novel approach that has not been extensively tested in this demographic.

Eligibility criteria

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.

Where this trial is running

Boadilla del Monte, Madrid

• HM Monteprincipe — Boadilla del Monte, Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Marta Osuna Marco MD, Medical Degree

Conditions Solid Tumor Cancer; Medulloblastoma; High Risk Neuroblastoma; High Grade Gliomas; Meningioma; Paraganglioma; Pheochromocytoma; Neuroendocrine Tumours