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

Vastra Gotaland Region

Status and phase

Active, not recruiting

Phase 1

Conditions

Clinical Trial, Phase I

Thymoma

Neuroendocrine Tumors

Mesothelioma

Treatments

Drug: 177Lu-DOTA-TATE + olaparib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04375267

2019-001700-37

Details and patient eligibility

About

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.

Enrollment

18 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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