Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

Официальное название

Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors. An Open-label, Multicenter, Randomized Phase III Trial Comparing Safety and Efficacy of Personalized Versus Non-personalized Radionuclide Therapy With 177Lu (Lutetium)-DOTATOC.

Обзор

There are several ways of personalizing PRRT (peptide receptor radionuclide treatment) in NEN (neuroendocrine neoplasia). Nevertheless, the current treatment regimen is not personalized. This trial aims to compare personalized PRRT to non-personalized PRRT in terms of safety, efficacy and resource demands in order to optimize treatment outcomes in an evidence-based manner in future.

Вмешательства

• Препарат 177Lu-DOTATOC
  The investigational medicinal product (IMP) is 177Lu-DOTATOC which is registered as an orphan drug by the EMA ( European Medicines Agency) for the treatment of GEP-NEN (gastro-entero-pancreatic neuroendocrine tumor). The IMP will be administered to participants both in the control arm and the experimental arms, but with different intervals, but the same activity; 7.5 Gbq per dosing.
• Препарат Capecitabine
  Will be given orally with a dose of 825/m2 twice daily, starting on day 1 of each of the 4 first treatment cycles, cycle length 3 weeks.

Первичные конечные точки

• Median progression free survival (PFS) defined as time from randomization to radiological progression. [Срок оценки: Before start of treatment (within 4 weeks), then every 10 +/- 2 weeks weeks, at follow up (every 3-6 month (investigators choice) until progression.]
• Median progression free survival (PFS) defined as time from randomization to radiological progression. [Срок оценки: Before start of treatment (within 4 weeks), then every 10 +/- week at follow up (every 3-6 month (investigators choice) until death.]
• Median progression free survival (PFS) defined as time from randomization to radiological progression, [Срок оценки: Before start of treatment (within 4 weeks), then every 10 +/- 2 weeks, at follow up (every 3-6 month (investigators choice) or patients withdrawal of concent.. No end can be given.]

Вторичные конечные точки (9)

• Rate of treatment-related adverse reactions [Срок оценки: At every treatment cycle, cycle length is 10 +/-2 weeks, at treatment follow up every 3-6 month (investigators choice) until progression. No time point can be given.]
• Median overall survival (OS). [Срок оценки: From date of randomization until the date of death. Timepoint unknown, as date of death can´t be predicted.]
• Progression free survival. [Срок оценки: From time of randomization until the date of first documented progression. Is evaluated within 4 weeks before randomization, after each treatment, every 10 +/2 weeks. Timepoint unknown, as date of progression can´t be predicted.]
• Percent change in sum of longest diameters (SLD) of tumor lesions. [Срок оценки: At each radiological investigation with CT or MRI of thorax and abdomen. Is done every 10 +/- 2 weeks. In the follow up period, evaluations are done every 3-6 months until death.]
• Quality of Life as judged by the patient. [Срок оценки: Patients complete the QoL forms before start of treatment, at cycle 2 (cycle length 10+/-2 weeks), at each treatment cycle (4-approximately 7), until progression.]
• Cumulative median absorbed dose (AD) [Срок оценки: After each dosimetry measurements after each treatment cycle (cycle length 10 +/2 weeks), up to 18 +/-2 months.]
• Correlation between cumulative median absorbed dose and time to progression. [Срок оценки: Every 10 +/- 2 weeks up to 18 +/- 2 months.]
• Cumulative median absorbed dose (AD) and biological effective dose to kidneys. [Срок оценки: Is evaluated with dosimetry after each treatment, 10 +/- 2 weeks, up to 18 +/- 2 months.]
• Differences in resource utilization and treatment cost. [Срок оценки: Through study completion, an average of 18 months, assessed every 10 +/- 2 weeks by questionnaires.]

Критерии участия

Критерии включения

• Age ≥18 years
• Written informed consent
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Presence of histologically confirmed, advanced, well-differentiated, inoperable neuroendocrine tumors (NET) of any primary tumor origin and any grade, except for pheochromocytoma and paraganglioma.
• Somatostatine receptor (SSTR)-expression in tumor lesions > basal liver uptake on 68Ga-DOTA-PET
• Radiologically progressive disease within the last 1-24 months according to common clinical criteria and confirmed by the institutional multidisciplinary conference for the treatment of NETs. The CT/MRI that shows tumor progression compared to screening/baseline must have been performed 1-24 months earlier.
• All previous anti-tumor treatment except SSA must be terminated at least 4 weeks before start of treatment within the trial.
• Measurable disease according to RECIST v 1.1
• Given the available, approved anti-tumor treatments and the specific characteristics of the patient and the tumor, the investigator judges peptide receptor radionuclide therapy (PRRT) to be the treatment of choice
• GFR > 50 ml/min/1.73 m2 as determined by iohexol- or 51Cr-EDTA clearance, calculated according to a combination of LMR18 and CAPA formulas, or equally accurate method
• Hemoglobin > 90 g/L, platelets >100 x109/L, leukocytes > 3.0x109/L, neutrophils > 1.5 x109/L, aspartate transaminase (ASAT)/alanine aminotransferase (ALAT) < 3 x ULN, bilirubin < 2 x upper limit of normal (ULN), albumin > 25 g/L
• For women of child-bearing potential, highly effective contraception should be used from the time of inclusion up to at least six months after the end of treatment (EOT) visit.

Критерии исключения

• Pregnancy or lactation
• Previous treatment with PRRT
• Concomitant systemic anti-tumor therapy other than somatostatin analogue (SSA)
• Contraindications for treatment with capecitabine according to the approved label.
• Discordance between CT/MRI/18F-FDG-PET and 68Ga-DOTA-PET, with evidence of tumor lesions without uptake on 68Ga-DOTATOC.
• Any other serious, uncontrolled medical or psychiatric condition that, in the opinion of the investigator, precludes the patient from participation in the trial
• Unwillingness, or inability, to participate in any part of the trial procedures or treatments.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швеция · 4 центра

• Sahlgrenska University Hospital, Dept. of Oncology — Gothenburg
• Skåne University Hospital, Dept. of Oncology — Lund
• Karolinska University Hospital, Dept. of Oncology — Stockholm
• Accademical Hospital, Uppsala, Dept. of Oncology — Uppsala

Идентификаторы

NCT: NCT05387603 · START-01 · 2021-002218-15

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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