Clinical trial NCT05053854: PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours
Official title: Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neuroendocrine Tumors
Keywords: NET
Lead sponsor: Peter MacCallum Cancer Centre, Australia
Sponsor class: OTHER
First posted: 2021-09-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective single arm, single centre, Phase 1 study
Primary purpose: TREATMENT

Brief summary: This phase 1 dose-escalation study is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate peptide receptor radionuclide therapy (PRRT) in patients with metastatic pancreatic or midgut neuroendocrine tumour (NET).

Detailed description: This phase 1, single arm, single centre study is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate in patients with metastatic NET.

Patients will receive 1 cycle of 177Lu-DOTA-Octreotate alone followed by 3 cycles of 177Lu-DOTA-Octreotate combined with 5 days of talazoparib.

Eligibility criteria: Inclusion Criteria:

1. Patient must be \> or equal to18 years of age and must have provided written informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
3. Histologically confirmed Grade 2 NET, Ki-67 of 3-20%, from pancreatic or intestinal origin.
4. Patient clinically suitable for PRRT
5. Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
6. No discordant FDG-avid disease on FDG PET/CT
7. No evidence of significant uncorrected carcinoid heart disease
8. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments
9. Patients must have adequate bone marrow, hepatic and renal function defined as:

   * Haemoglobin ≥100 g/L
   * Absolute neutrophil count ≥1.5x109/L
   * Platelets ≥150 x109/L
   * Total bilirubin ≤1.5 x upper limit of normal (ULN)
   * Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT)

     ≤2.5 x ULN if there is no evidence of liver metastasis or ≤5 x ULN in the presence of liver metastases.
   * Albumin ≥ 30 g/L
   * Adequate renal function: eGFR ≥ 50 ml/min

Exclusion Criteria:

1. Surgery or radiotherapy within \<3 weeks of registration. Patients must have recovered from any effects of any major surgery.
2. Any prior exposure to peptide receptor radionuclide therapy (177Lu, 111In or 90Y labelled), PARPi, immunotherapy
3. Uncontrolled intercurrent illness that is likely to impede participation and /or compliance
4. Other malignancies unless curatively treated with no evidence of disease within previous 3-years other than adequately treated non-melanoma skin cancer or melanoma in situ.
5. Previous or current history of myelodysplastic syndrome/acute myeloid leukemia
6. Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication.
7. Use of strong P-gp inhibitors (eg, dronedarone, quinidine, ranolazine, verapamil, ketoconazole, itraconazole), P-gp inducers (eg, rifampin, tipranavir/ritonavir), or BCRP inhibitors (eg, elacridar \[GF120918\]) should be avoided.
8. Participation in another clinical study with an investigational product or another systemic therapy administered in the last 3 weeks (except short acting SSA).

Primary outcomes:
measure: Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
timeFrame: Through study completion, up to 18 months following first administration of PRRT.
measure: Dose limiting toxicity talazoparib
timeFrame: Each cohort of 3 patients be assessed for DLTs in the first 6 weeks (cycle 2) of treatment and a dose for the next cohort will be determined (each cycle is 8 weeks)
Secondary outcomes:
measure: Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
timeFrame: Through Study completion, up to 18 months after the last patient commences treatment.
measure: Radiographic progression free survival
timeFrame: Through study completion, up to 18 months following first administration of PRRT.
measure: Overall Survival
timeFrame: Through study completion, up to 18 months following first administration of PRRT.
measure: Treatment discontinuation due to toxicity
timeFrame: Through study completion, up to 18 months following first administration of PRRT.
measure: Rate of Treatment discontinuation due to toxicity
timeFrame: Through study completion, up to 18 months following first administration of PRRT.
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
References: