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

Official title

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)

Overview

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

• Phase II: Duration of Response (DOR) per investigator [Time frame: Up to 3 years]
• Phase II: Disease Control Rate (DCR) per investigator [Time frame: Up to 3 years]
• Phase II: Progression Free Survival (PFS) per investigator [Time frame: Up to 3 years]
• Phase II: Overall Survival (OS) [Time frame: Up to 3 years]
• Peak Concentration：Cmax [Time frame: Up to 3 years]
• Area under the plasma concentration-time curve: AUC [Time frame: Up to 3 years]
• Half-Life: t1/2 [Time frame: Up to 3 years]
• Phase II: Blood concentrations and PK parameters of sirolimus for injection(albumin bound) and Octreotide long-acting injection. [Time frame: 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. [Time frame: From first dose of treatment to end of treatment]
• Phase III: Progression Free Survival (PFS) per investigator [Time frame: Up to 3 years]
• Phase III: Objective Response Rate (ORR） [Time frame: Up to 3 years]
• Phase III: Duration of Response (DOR) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Chinese PLA General Hospital — Beijing

Identifiers

NCT: NCT07165886 · HB1901-010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗