Gastroenteropancreatic Neuroendocrine Tumors
Conditions
Brief summary
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
Sirolimus for injection (albumin bound), ivgtt.
DRUGOctreotide long-acting injection
SC
DRUGEverolimus
Oral, once a day
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase II: Incidences of Adeverse Events (AEs) | Up to 3 years |
| Phase II: Dose Limiting Toxicity (DLT) | Up to 1 year |
| Phase II: Recommended Phase 3 Dose (RP3D) | Up to 1 year |
| Phase II: Objective Response Rate (ORR） per investigator | Up to 1 year |
| Phase III: Progression Free Survival (PFS) per Blinded Independent Review Committee (BIRC) | Up to 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Phase II: Duration of Response (DOR) per investigator | Up to 3 years |
| Phase II: Disease Control Rate (DCR) per investigator | Up to 3 years |
| Phase II: Progression Free Survival (PFS) per investigator | Up to 3 years |
| Phase II: Overall Survival (OS) | Up to 3 years |
| Peak Concentration：Cmax | Up to 3 years |
| Area under the plasma concentration-time curve: AUC | Up to 3 years |
| Half-Life: t1/2 | Up to 3 years |
| Phase II: Blood concentrations and PK parameters of sirolimus for injection(albumin bound) and Octreotide long-acting injection. | 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. | From first dose of treatment to end of treatment |
| Phase III: Progression Free Survival (PFS) per investigator | Up to 3 years |
| Phase III: Objective Response Rate (ORR） | Up to 3 years |
| Phase III: Duration of Response (DOR) | Up to 3 years |
| Phase III: Disease Control Rate (DCR) | Up to 3 years |
| Phase III: Incidences of Adeverse Events (AEs) | Up to 3 years |
| Phase III: Overall Survival (OS) | Up to 3 years |
| Phase III: Changes in serum chromogranin A, 24-hour urinary 5-hydroxyindoleacetic acid, and serum IGF-1 levels from baseline. | From first dose of treatment to end of treatment |
Countries
China
Contacts
CONTACTClinical Trials Information Group officer
Outcome results
None listed