Neuroendocrine TumorsPhase 1PRRT-PARPiNCT05870423
Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors
A Phase 1 study testing olaparib in people with Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
This is a phase 1 dose-escalation study to determine the maximum tolerated dose of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced gastroenteropancreatic NET (GEP NET), progressive after PRRT. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Peptide Receptor Radionuclide Therapy
- What is being tested?
- olaparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jun 2022to 1 Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven locally advanced or metastatic, well-differentiated (grade 1, 2 or 3) NET.
- Disease progression based on RECIST v1.1 following initial or salvage treatment with PRRT with 177Lu-DOTATATE with a progression free interval of at least 12 months since first cycle of previous administration of PRRT or with no suitable systemic alternative treatment options.
- The patient is eligible for two cycles of salvage PRRT.
- Measurable disease according to RECIST v1.1 on CT/MRI.
- Confirmed presence of somatostatin receptors on all target lesions on CT/MRI, based on positive uptake on a 68Ga-DOTATATE/-TOC/-NOC PET-CT/MRI scan.
- Age ≥ 18 years.
- Karnofsky Performance Score (KPS) > 60.
Who cannot join
- Hb concentration <6.2 mmol/L; white blood cell count <3x109/L; platelets <100x109/L; neutrophil count <1.5x109/L.
- Renal insufficiency defined as a creatinine clearance <50 mL/min, measured in 24-hour urine collection.
- Liver function or enzyme abnormalities defined as a total bilirubin >3 x ULN, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN or serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
- Pregnancy, lactation and inability to comply with effective means of contraception in females of child-bearing age.
- Neuroendocrine carcinoma of any origin.
- Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to inclusion in the study. Interferons, everolimus, sunitinib or other systemic therapies within 4 weeks prior to inclusion in the study.
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- Uncontrolled congestive heart failure (NYHA II, III, IV).
- Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
- Prior external beam radiation therapy to more than 25% of the bone marrow.
- Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
- Patients who use a strong CYP3A4 inhibitor within 1 week before start of the treatment or a CYP3A4 inducer within 4 weeks before start of the treatment.
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- Known allergy or intolerance for the (non-)investigational drugs.
- Inability to provide informed consent.
- End of life care.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus MC
Rotterdam, South Holland, 3000CA
M.N. Becx, 43449, m.becx@erasmusmc.nl
About this study
This is a phase 1 dose-escalation study to determine the maximum tolerated dose of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced gastroenteropancreatic NET (GEP NET), progressive after PRRT. As secondary objectives, efficacy, pharmacokinetics and biomarker response will be investigated.
Read the detailed description
Rationale:
Peptide receptor radionuclide therapy (PRRT) with the beta-emitting radiopharmaceutical 177Lutetium-DOTA-Tyr3,octreotate (177Lu-DOTATATE) is an effective and safe treatment option for patients with metastatic neuroendocrine tumors (NETs). In advanced NET patients, 177Lu-DOTATATE has been proven to secure long-term survival in several large retrospective series and was superior to high-dose somatostatin analogs in a randomized phase 3 clinical trial, with a 79% decrease in the risk of progression or death. However, objective response rates are limited and fewer than 1% of the patients can achieve complete response following PRRT. Administering a higher cumulative dose than currently applied will induce more toxicity in healthy tissues and probably will be detrimental to patients. Therefore, adaptations to the currently applied PRRT regimen are needed.
The repair of PRRT-induced DNA damage constitutes a viable target to enhance its antitumor effects. In a number of preclinical models, inhibitors of the enzyme poly ADP ribose polymerase (PARP), essential for repair of single-strand DNA breaks, have been shown to improve the cytotoxic effects of PRRT without signs of added toxicity. Various PARP inhibitors are registered for the treatment of human cancers, such as ovarian cancer, and BRCA- or homologous repair deficiency (HRD)-dependent prostate and pancreatic cancer and are under investigation in several clinical trials as radiosensitizer. Based on preclinical in vitro and in vivo data, we hypothesize that PARP inhibitors can potentiate radiation-induced tumor cell death in patients treated with PRRT. This therapeutic combination has not been studied in human subjects before.
Objective:
To determine the maximum tolerated dose (MTD) of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced NET, progressive after PRRT.
Study design:
Phase I dose escalation, single arm, prospective single center study.
Study population:
Patients with locally advanced or metastatic NETs that have progressive disease according to RECIST v1.1 following initial or salvage PRRT and are considered for two additional PRRT cycles of standard 7.4 GBq each.
Intervention:
Patients eligible for retreatment with PRRT will receive the PARP inhibitor olaparib starting 3 days before each dose of 7.4 GBq 177Lu-DOTATATE until 2 weeks thereafter. The dose of olaparib will be increased from 100 mg q.d. to 300 mg b.i.d. in subsequent patients in 4 preplanned dose escalation steps. In case of unexpected toxicity at the start dose, a de-escalation step to 50 mg q.d. is allowed. The study is performed according to the classic phase I 3+3 dose escalation design with initially 3 patients per dose level. If no dose-limiting toxicity (DLT) is observed in 3 consecutive patients, the dose will be increased to the next planned dose-level. In case of 1 DLT, inclusion of up to 3 additional patients at the same dose is pursued, after which dose escalation can follow if no additional DLT is observed. In case of ≥2/6 DLTs at a given dose level, further dose escalation will be stopped and an additional 3 patients will be treated at the next lower dose level in order to establish a recommended phase II dose (R2PD) for further testing.
Main study parameters/endpoints:
Primary endpoints:
- Incidence and severity of adverse events according to CTCAE v5.0
- Determination of the MTD of olaparib in combination with standard dose PRRT
Secondary endpoints:
- Progression-free and overall survival
- Response rate
- Olaparib pharmacokinetic parameters
- Pharmacokinetic/-dynamic influence of olaparib on 177Lu-DOTATATE
- Measurement of antitumor effects in freshly acquired tumor biopsies
- Being tested
- olaparib
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olaparibDrug
Also called Lynparza
18 days olaparib during each cycle of PRRT
| Study group | Role | What they receive |
|---|---|---|
| PRRT + olaparib 100mg q.d. | Experimental | administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 100mg q.d. Receives: Drug: olaparib |
| PRRT + olaparib 100mg b.i.d. | Experimental | administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 100mg b.i.d. Receives: Drug: olaparib |
| PRRT + olaparib 200mg b.i.d. | Experimental | administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 200mg b.i.d. Receives: Drug: olaparib |
| PRRT + olaparib 300mg b.i.d. | Experimental | administration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 300mg b.i.d. Receives: Drug: olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Incidence and severity of adverse events according to CTCAE v5.0
Measured: 3 years
Maximum tolerated dase
Determination of the MTD of olaparib in combination with standard dose PRRT
Measured: 3 years
Secondary outcomes (3)
Survival rates
Progression-free and overall survival
Measured: 3 years
Best response
Response rate
Measured: 3 years
Antitumor effects
Measurement of antitumor effects in freshly acquired tumor biopsies. DNA damage, transcriptomics and PARylation will be measured in blood and tumor biopsies
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start1 Jun 2022
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 3+3 dose-escalation.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Morticia N. Becx, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05870423
- Sponsor's protocol ID
- NL79259.078.21
- Acronym
- PRRT-PARPi
- Status last verified
- May 2025
- First submitted
- 6 Apr 2023
- Last updated
- 5 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors
- ClinicalTrials.gov ID
- NCT05870423
- Acronym / sponsor ID
- PRRT-PARPi / NL79259.078.21
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 23 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1 dose-escalation study to determine the maximum tolerated dose of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced gastroenteropancreatic NET (GEP NET), progressive after PRRT. As secondary objectives, efficacy, pharmacokinetics and biomarker response will be investigated.
Detailed description
Rationale:
Peptide receptor radionuclide therapy (PRRT) with the beta-emitting radiopharmaceutical 177Lutetium-DOTA-Tyr3,octreotate (177Lu-DOTATATE) is an effective and safe treatment option for patients with metastatic neuroendocrine tumors (NETs). In advanced NET patients, 177Lu-DOTATATE has been proven to secure long-term survival in several large retrospective series and was superior to high-dose somatostatin analogs in a randomized phase 3 clinical trial, with a 79% decrease in the risk of progression or death. However, objective response rates are limited and fewer than 1% of the patients can achieve complete response following PRRT. Administering a higher cumulative dose than currently applied will induce more toxicity in healthy tissues and probably will be detrimental to patients. Therefore, adaptations to the currently applied PRRT regimen are needed.
The repair of PRRT-induced DNA damage constitutes a viable target to enhance its antitumor effects. In a number of preclinical models, inhibitors of the enzyme poly ADP ribose polymerase (PARP), essential for repair of single-strand DNA breaks, have been shown to improve the cytotoxic effects of PRRT without signs of added toxicity. Various PARP inhibitors are registered for the treatment of human cancers, such as ovarian cancer, and BRCA- or homologous repair deficiency (HRD)-dependent prostate and pancreatic cancer and are under investigation in several clinical trials as radiosensitizer. Based on preclinical in vitro and in vivo data, we hypothesize that PARP inhibitors can potentiate radiation-induced tumor cell death in patients treated with PRRT. This therapeutic combination has not been studied in human subjects before.
Objective:
To determine the maximum tolerated dose (MTD) of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced NET, progressive after PRRT.
Study design:
Phase I dose escalation, single arm, prospective single center study.
Study population:
Patients with locally advanced or metastatic NETs that have progressive disease according to RECIST v1.1 following initial or salvage PRRT and are considered for two additional PRRT cycles of standard 7.4 GBq each.
Intervention:
Patients eligible for retreatment with PRRT will receive the PARP inhibitor olaparib starting 3 days before each dose of 7.4 GBq 177Lu-DOTATATE until 2 weeks thereafter. The dose of olaparib will be increased from 100 mg q.d. to 300 mg b.i.d. in subsequent patients in 4 preplanned dose escalation steps. In case of unexpected toxicity at the start dose, a de-escalation step to 50 mg q.d. is allowed. The study is performed according to the classic phase I 3+3 dose escalation design with initially 3 patients per dose level. If no dose-limiting toxicity (DLT) is observed in 3 consecutive patients, the dose will be increased to the next planned dose-level. In case of 1 DLT, inclusion of up to 3 additional patients at the same dose is pursued, after which dose escalation can follow if no additional DLT is observed. In case of ≥2/6 DLTs at a given dose level, further dose escalation will be stopped and an additional 3 patients will be treated at the next lower dose level in order to establish a recommended phase II dose (R2PD) for further testing.
Main study parameters/endpoints:
Primary endpoints:
- Incidence and severity of adverse events according to CTCAE v5.0
- Determination of the MTD of olaparib in combination with standard dose PRRT
Secondary endpoints:
- Progression-free and overall survival
- Response rate
- Olaparib pharmacokinetic parameters
- Pharmacokinetic/-dynamic influence of olaparib on 177Lu-DOTATATE
- Measurement of antitumor effects in freshly acquired tumor biopsies
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 3+3 dose-escalation.
| Arm | Type | Receives |
|---|---|---|
| PRRT + olaparib 100mg q.d. | Experimental | Drug: olaparibadministration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 100mg q.d. |
| PRRT + olaparib 100mg b.i.d. | Experimental | Drug: olaparibadministration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 100mg b.i.d. |
| PRRT + olaparib 200mg b.i.d. | Experimental | Drug: olaparibadministration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 200mg b.i.d. |
| PRRT + olaparib 300mg b.i.d. | Experimental | Drug: olaparibadministration of the standard therapy of 7.4GBq 177lu-dotatate with the additional study medication olaparib 300mg b.i.d. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically proven locally advanced or metastatic, well-differentiated (grade 1, 2 or 3) NET.
- Disease progression based on RECIST v1.1 following initial or salvage treatment with PRRT with 177Lu-DOTATATE with a progression free interval of at least 12 months since first cycle of previous administration of PRRT or with no suitable systemic alternative treatment options.
- The patient is eligible for two cycles of salvage PRRT.
- Measurable disease according to RECIST v1.1 on CT/MRI.
- Confirmed presence of somatostatin receptors on all target lesions on CT/MRI, based on positive uptake on a 68Ga-DOTATATE/-TOC/-NOC PET-CT/MRI scan.
Key exclusion criteria (15 listed)
- Hb concentration <6.2 mmol/L; white blood cell count <3x109/L; platelets <100x109/L; neutrophil count <1.5x109/L.
- Renal insufficiency defined as a creatinine clearance <50 mL/min, measured in 24-hour urine collection.
- Liver function or enzyme abnormalities defined as a total bilirubin >3 x ULN, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN or serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
- Pregnancy, lactation and inability to comply with effective means of contraception in females of child-bearing age.
- Neuroendocrine carcinoma of any origin.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| olaparibAlso: Lynparza18 days olaparib during each cycle of PRRT | Drug | PRRT + olaparib 100mg b.i.d., PRRT + olaparib 100mg q.d., PRRT + olaparib 200mg b.i.d., PRRT + olaparib 300mg b.i.d. |
Primary outcome
Adverse events
Time frame: 3 years
Incidence and severity of adverse events according to CTCAE v5.0
Maximum tolerated dase
Time frame: 3 years
Determination of the MTD of olaparib in combination with standard dose PRRT
3 secondary outcomes
Survival rates
Time frame: 3 years
Best response
Time frame: 3 years
Antitumor effects
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing olaparib in people with Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact M.N. Becx (43449, m.becx@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025.