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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04375267
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Vastra Gotaland Region
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries Sweden
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Clinical Trial, Phase I, Neuroendocrine Tumors, Thymoma, Mesothelioma
Arms & Interventions

Arms

Experimental: 177Lu-DOTA-TATE and olaparib

Interventions

Drug: - 177Lu-DOTA-TATE + olaparib

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Dept of Oncology, Gothenburg, Sweden

Status

Recruiting

Address

Dept of Oncology

Gothenburg, , 41345

Site Contact

Andreas Hallqvist

andreas.hallqvist@vgregion.se

+46313421000

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