Brief Title
177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours
Official Title
Phase I Trial With 177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Secondary Outcome
TTP
Condition
Clinical Trial, Phase I
Intervention
177Lu-DOTA-TATE + olaparib
Study Arms / Comparison Groups
177Lu-DOTA-TATE and olaparib
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
18
Start Date
April 23, 2020
Completion Date
June 30, 2023
Primary Completion Date
June 30, 2022
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, +46313421000, [email protected]
Location Countries
Sweden
Location Countries
Sweden
Administrative Informations
NCT ID
NCT04375267
Organization ID
2019-001700-37
Responsible Party
Sponsor
Study Sponsor
Vastra Gotaland Region
Collaborators
Advanced Accelerator Applications
Study Sponsor
, ,
Verification Date
April 2020