LuPARP: 177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [up to 6 months after last treatment cycle]
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
Secondary Outcome Measures
- TTP [3 years]
Time to progression
- Response rate [12 months after last treatment cycle]
Response rate (RECIST) at 3 and 12 months
- OS [3 years]
Overall survival
- DOR [3 years]
Duration of response
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histological or cytological diagnosis of neoplasia (not mandatory for meningioma)
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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
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Evidence of regional or distant metastases or localised disease not accessible for complete resection
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Measurable disease according to RECIST 1.1
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Evidence of somatostatin receptor positive disease detected by 68Ga-DOTA-TATE/TOC PET
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Progressive disease during the last 14 months based on CT or new lesions detected by 68Ga-DOTA-TATE PET.
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Performance status ECOG 0 - 1
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Life expectancy > 6 months
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Age >18 years, no upper age limit.
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Neutrophil count >1,5 x 109/L
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Platelet count >100 x 109/L
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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.
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GFR > 50 ml/min
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Written informed consent from patients
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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:
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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).
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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:
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Performance Status ECOG > 1
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Well differentiated GEPNETs grad 1 and 2 (except aggressive grade 2 tumours with a poor prognosis and a Ki67 > 15%)
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Loco-regional treatment during the last 3 months involving all of the measurable lesions
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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
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Previous treatment with 177Lu-DOTA-TATE or cis-/carboplatin
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Other concomitant nephrotoxic treatment
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Serious heart disease (NYHA III-IV)
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Previous radiotherapy including >25% of active bone marrow volume
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Pregnancy and lactation
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Extensive liver metastases combined with impaired liver function (i.e. abnormal laboratory parameters (> grad 1 CTCAE) or ascites)
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Symptomatic CNS metastases (e.g. requiring corticosteroid treatment) Symptomatic treatment for meningiomas or corticosteroids due to treatment related swelling is however allowed
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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
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Patients who have a another metastatic tumor diagnosis
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Known or expected hypersensitivity to 177Lu-DOTA-TATE, 68Ga- DOTA-TATE/TOC or any of their excipients
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History of psychiatric disease/condition that may interfere with the objectives and assessments of the study
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dept of Oncology | Gothenburg | Sweden | 41345 |
Sponsors and Collaborators
- Vastra Gotaland Region
- Advanced Accelerator Applications
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019-001700-37