Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors

Официальное название

Phase II/III Study to Evaluate the Safety and Efficacy of Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Обзор

There is limited evidence regarding the benefit of adding somatostatin analogs to molecular targeted agents for well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with poor prognostic factors. This trial is conducted to evaluate sirolimus for injection (albumin bound) combined with octreotide long-acting injection in patients with unresectable or recurrent GEP-NETs.

Вмешательства

• Препарат Sirolimus for injection (albumin bound)
  Sirolimus for injection (albumin bound), ivgtt.
• Препарат Octreotide long-acting injection
  SC
• Препарат Everolimus
  Oral, once a day

Первичные конечные точки

• Phase II: Incidences of Adeverse Events (AEs) [Срок оценки: Up to 3 years]
• Phase II: Dose Limiting Toxicity (DLT) [Срок оценки: Up to 1 year]
• Phase II: Recommended Phase 3 Dose (RP3D) [Срок оценки: Up to 1 year]
• Phase II: Objective Response Rate (ORR） per investigator [Срок оценки: Up to 1 year]
• Phase III: Progression Free Survival (PFS) per Blinded Independent Review Committee (BIRC) [Срок оценки: Up to 3 years]

Вторичные конечные точки (12)

• Phase II: Duration of Response (DOR) per investigator [Срок оценки: Up to 3 years]
• Phase II: Disease Control Rate (DCR) per investigator [Срок оценки: Up to 3 years]
• Phase II: Progression Free Survival (PFS) per investigator [Срок оценки: Up to 3 years]
• Phase II: Overall Survival (OS) [Срок оценки: Up to 3 years]
• Peak Concentration：Cmax [Срок оценки: Up to 3 years]
• Area under the plasma concentration-time curve: AUC [Срок оценки: Up to 3 years]
• Half-Life: t1/2 [Срок оценки: Up to 3 years]
• Phase II: Blood concentrations and PK parameters of sirolimus for injection(albumin bound) and Octreotide long-acting injection. [Срок оценки: From first dose of treatment to C3D15]
• Phase II: Changes in serum chromogranin A, 24-hour urinary 5-hydroxyindoleacetic acid, and serum IGF-1 levels from baseline. [Срок оценки: From first dose of treatment to end of treatment]
• Phase III: Progression Free Survival (PFS) per investigator [Срок оценки: Up to 3 years]
• Phase III: Objective Response Rate (ORR） [Срок оценки: Up to 3 years]
• Phase III: Duration of Response (DOR) [Срок оценки: Up to 3 years]

Критерии участия

Критерии включения

• 1\. Unresectable locally advanced or metastatic G1/G2 GEP-NETs diagnosed by histology, according to the 2019 WHO histological grading criteria.
• 2\. Having poor prognostic factors.
• 3\. Non-functional GEP-NETs are required.
• 4\. At least one evaluable lesion meets the RECIST V1.1 standard (Applicable only to the phase II safety run-in stage)
• 6\. ECOG 0\~2.
• 7\. Organ function reserve is good.
• 8\. Be able to sign a written informed consent form.

Критерии исключения

• 1\. Patients who have previously received SSTR-targeted therapies (including somatostatin analogs \[SSAs\] and peptide receptor radionuclide therapy) and/or mTOR inhibitors (Patients who received SSAs in the adjuvant setting and experienced recurrence ≥6 months after treatment completion may be enrolled)\[ Applicable to Phase II dose expansion and Phase III stages\].
• 2\. Has uncontrolled/severe diarrhea or an axillary temperature > 38.0°C at enrollment.
• 3\. Received treatment with other unlisted clinical investigational drugs within 4 weeks prior to the first use of the investigational drug.
• 4\. Undergone major surgical procedures within 4 weeks prior to the first use of the investigational drug and have not fully recovered.
• 5\. Received systemic use of corticosteroids or other immunosuppressive therapy within 2 weeks prior to the first use of the study drug.
• 6\. With an infection that requires systemic anti-infective treatment within 2 weeks prior to the first use of the study drug.
• 7\. Those who have used strong inhibitors or inducers of CYP3A4 liver metabolic enzymes within 2 weeks prior to the first use of the investigational drug or still need to continue using such drugs.
• 8\. Has a serious history of cardiovascular and cerebrovascular diseases.
• 9\. Having active brain metastasis and/or malignant meningitis.
• 10\. With a history of severe lung diseases.
• 11\. During screening, there may be symptomatic gallstones or a history of symptomatic gallstones but no surgical treatment has been performed.
• 12\. Abnormal thyroid function during screening.
• 13\. Known to have hypersensitivity reactions or intolerance to any component of all investigational drugs or their excipients.
• 14\. Active hepatitis B, active hepatitis C virus infection, or active syphilis infection.
• 15\. History of autoimmune diseases (excluding tuberous sclerosis), history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.

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

Китай · 1 центр

• Chinese PLA General Hospital — Пекин

Идентификаторы

NCT: NCT07165886 · HB1901-010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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