177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours

NCT04375267 | Completed Phase 1

• 1 other identifier: 2019-001700-37
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study of 177Lu-DOTA-TATE in combination with the PARP-inhibitor olaparib for treatment of patients with somatostatin receptor positive tumours detected by 68Ga-DOTA-TATE/TOC PET. The combination of a PARP inhibitor that will specifically target the repair mechanism, with ionising radiation causing SSB's might overcome the repair dependent survival of the tumour cells, making them more sensitive to β-emission and increase the probability of tumour cell death.

Conditions

Clinical Trial, Phase I; Neuroendocrine Tumors; Thymoma; Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  To assess the number of participants with toxicity of 177Lu-DOTA-TATE in combination with olaparib measured by NCI Common Toxicity Criteria v 5.0

  up to 6 months after last treatment cycle

Secondary Outcomes (4)

• TTP

  3 years

• Response rate

  12 months after last treatment cycle

• OS

  3 years

• DOR

  3 years

Study Arms (1)

177Lu-DOTA-TATE and olaparib

EXPERIMENTAL

Drug: 177Lu-DOTA-TATE + olaparib

Interventions

177Lu-DOTA-TATE + olaparib DRUG

177Lu-DOTA-TATE in four cycles in combination with escalated doses of olaparib

177Lu-DOTA-TATE and olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological diagnosis of neoplasia (not mandatory for meningioma)
• GEPNETs grade 3 or aggressive grade 2 tumours with a poor prognosis and a Ki67 \> 15% OR neuroendocrine tumours NOS after standard therapy OR thymomas/tumours of other origin after standard therapy OR meningiomas after standard therapy not suitable for surgery or radiotherapy
• Evidence of regional or distant metastases or localised disease not accessible for complete resection
• Measurable disease according to RECIST 1.1
• Evidence of somatostatin receptor positive disease detected by 68Ga-DOTA-TATE/TOC PET
• Progressive disease during the last 14 months based on CT or new lesions detected by 68Ga-DOTA-TATE PET.
• Performance status ECOG 0 - 1
• Life expectancy \> 6 months
• Age \>18 years, no upper age limit.
• Neutrophil count \>1,5 x 109/L
• Platelet count \>100 x 109/L
• Normal liver function regarding transaminases, PK and albumin. A raised bilirubin which can be considered an isolated effect of liver metastases is not a contraindication as long as the levels remain \<1.5 x ULN.
• GFR \> 50 ml/min
• Written informed consent from patients
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

You may not qualify if:

• Performance Status ECOG \> 1
• Well differentiated GEPNETs grad 1 and 2 (except aggressive grade 2 tumours with a poor prognosis and a Ki67 \> 15%)
• Loco-regional treatment during the last 3 months involving all of the measurable lesions
• Chemotherapy during the last 8 weeks or longer until no persisting toxicity exists. Earlier treatment with mTORi or TKI the last 4 weeks or until no persisting toxicity exists
• Previous treatment with 177Lu-DOTA-TATE or cis-/carboplatin
• Other concomitant nephrotoxic treatment
• Serious heart disease (NYHA III-IV)
• Previous radiotherapy including \>25% of active bone marrow volume
• Pregnancy and lactation
• Extensive liver metastases combined with impaired liver function (i.e. abnormal laboratory parameters (\> grad 1 CTCAE) or ascites)
• Symptomatic CNS metastases (e.g. requiring corticosteroid treatment) Symptomatic treatment for meningiomas or corticosteroids due to treatment related swelling is however allowed
• Ongoing treatment with interferon. This treatment should be suspended a minimum of 4 wees before treatment with 177Lu-DOTA-TATE, or longer if there is persisting signs of toxicity
• Patients who have a another metastatic tumor diagnosis
• Known or expected hypersensitivity to 177Lu-DOTA-TATE, 68Ga- DOTA-TATE/TOC or any of their excipients
• History of psychiatric disease/condition that may interfere with the objectives and assessments of the study

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Advanced Accelerator Applications: collaborator

Study Sites (1)

Dept of Oncology

Gothenburg, 41345, Sweden

Location

Related Publications (1)

• Hallqvist A, Svensson J, Hagmarker L, Marin I, Ryden T, Beauregard JM, Bernhardt P. Optimizing the Schedule of PARP Inhibitors in Combination with 177Lu-DOTATATE: A Dosimetry Rationale. Biomedicines. 2021 Oct 29;9(11):1570. doi: 10.3390/biomedicines9111570.

  PMID: 34829796 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Thymoma; Mesothelioma

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: May 5, 2020
• Study Start: April 23, 2020
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

SE (1)