177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours (LuPARP)
Primary Purpose
Clinical Trial, Phase I, Neuroendocrine Tumors, Thymoma
Status
Unknown status
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
177Lu-DOTA-TATE + olaparib
Sponsored by
About this trial
This is an interventional treatment trial for Clinical Trial, Phase I
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
Sites / Locations
- Dept of OncologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
177Lu-DOTA-TATE and olaparib
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
TTP
Time to progression
Response rate
Response rate (RECIST) at 3 and 12 months
OS
Overall survival
DOR
Duration of response
Full Information
NCT ID
NCT04375267
First Posted
April 27, 2020
Last Updated
May 3, 2020
Sponsor
Vastra Gotaland Region
Collaborators
Advanced Accelerator Applications
1. Study Identification
Unique Protocol Identification Number
NCT04375267
Brief Title
177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours
Acronym
LuPARP
Official Title
Phase I Trial With 177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 23, 2020 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vastra Gotaland Region
Collaborators
Advanced Accelerator Applications
4. Oversight
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
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinical Trial, Phase I, Neuroendocrine Tumors, Thymoma, Mesothelioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
177Lu-DOTA-TATE and olaparib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
177Lu-DOTA-TATE + olaparib
Intervention Description
177Lu-DOTA-TATE in four cycles in combination with escalated doses of olaparib
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
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
Time Frame
up to 6 months after last treatment cycle
Secondary Outcome Measure Information:
Title
TTP
Description
Time to progression
Time Frame
3 years
Title
Response rate
Description
Response rate (RECIST) at 3 and 12 months
Time Frame
12 months after last treatment cycle
Title
OS
Description
Overall survival
Time Frame
3 years
Title
DOR
Description
Duration of response
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andreas Hallqvist, MD, PhD
Phone
+46313421000
Email
andreas.hallqvist@vgregion.se
First Name & Middle Initial & Last Name or Official Title & Degree
Annika Baan
Phone
+46313421000
Email
annika.baan@vgregion.se
Facility Information:
Facility Name
Dept of Oncology
City
Gothenburg
ZIP/Postal Code
41345
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Hallqvist
Email
andreas.hallqvist@vgregion.se
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34829796
Citation
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.
Results Reference
derived
Learn more about this trial
177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours
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