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

Phase I Trial With 177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours

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.

Study Overview

• Status: Completed
• Conditions: Thymoma; Neuroendocrine Tumors; Mesothelioma; Clinical Trial, Phase I
• Intervention / Treatment: Drug: 177Lu-DOTA-TATE + olaparib

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, 41345
    • Dept of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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:

  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Exclusion Criteria:

• 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
• Female subjects who are pregnant or breastfeeding or subjects of reproductive potential who are not willing to employ effective birth control methods (Pearl index <1) from screening to 6 months after the last dose of olaparib

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 177Lu-DOTA-TATE and olaparib	Drug: 177Lu-DOTA-TATE + olaparib; 177Lu-DOTA-TATE in four cycles in combination with escalated doses of olaparib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	3 years
TTP	Time to progression	3 years
Response rate	Response rate (RECIST) at 3 and 12 months	12 months after last treatment cycle
DOR	Duration of response	3 years

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Advanced Accelerator Applications

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: May 3, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Lymphatic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Thymus Neoplasms; Hemic and Lymphatic Diseases; Mesothelioma; Neuroendocrine Tumors; Thymoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Radiopharmaceuticals; Poly(ADP-ribose) Polymerase Inhibitors; olaparib
• Other Study ID Numbers: 2019-001700-37

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