Phase IV Study of the Safety and Efficacy of Everolimus in Adult Patients With Progressive pNET in China

Phase IV, Open-label, Multi-center, Single-arm Study of the Safety and Efficacy of Everolimus (Afinitor) in Adult Patients With Locally Advanced, Unresectable or Metastatic, Well Differentiated Progressive Pancreatic Neuroendocrine Tumors (pNET) in China.

To evaluate safety and efficacy of everolimus (Afinitor®) in Chinese adult patients with local advanced or metastatic, well differentiated progressive pancreatic neuroendocrine tumors.

Study Overview

• Status: Completed
• Conditions: Pancreatic Neuroendocrine Tumors
• Intervention / Treatment: Drug: everolimus

Detailed Description

This was an open-label, multicenter, single-arm clinical study to evaluate the safety and efficacy of everolimus in Chinese adult patients with locally advanced, unresectable or metastatic, well differentiated progressive pancreatic neuroendocrine tumors. The inclusion and exclusion criteria, as well as the dosing and dose modification criteria are designed according to the approved Chinese Package Insert. The planned sample size of the study was approximately 60 subjects.

Subjects who were eligible received the treatment with everolimus provided by sponsor to treat pNET and followed the visit schedule in the protocol to collect safety and efficacy data until progression of disease, unacceptable toxicity, death, protocol deviation or other reason that may lead to discontinuation before the end of study. All subjects were followed-up for survival status every 6 months by the investigator until death, lost to follow-up, withdrawal of consent for survival or end of study.

The "End of study" is defined as either at least 75% of subjects have completed survival follow up or all subjects discontinued study treatment or the last subject finished 5-year survival follow up, whichever comes first. Final analysis was conducted at the end of the study.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100039
    • Novartis Investigative Site
  • Guangzhou, China, 510060
    • Novartis Investigative Site
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histological confirmed G1 or G2 pancreatic neuroendocrine tumors(pNETs) (WHO 2010)
• Patients must have radiological documentation of progression of disease per RECIST 1.1 within 12 months prior to enrollment.
• Measurable disease per RECIST 1.1 criteria using triphasic computed tomography (CT) scan or multiphase MRI for radiologic assessment.
• everolimus treatment which is recommended by the treating physician

Exclusion Criteria:

• Hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients.
• Patient who is unwilling to receive Afinitor treatment due to any reason.
• Pregnant or nursing (lactating) women,
• Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus).
• Use of an investigational drug within the 30 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: everolimus (single arm); Participants were instructed to take everolimus at a starting dose of 10 mg orally once daily. However, dose adjustments were permitted in order to allow the participant to continue the study treatment.	Drug: everolimus; Participants were instructed to take everolimus at a starting dose of 10 mg orally once daily. However, dose adjustments were permitted in order to allow the participant to continue the study treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with treatment emergent adverse events (any AE regardless of seriousness), SAEs, AEs and SAEs on grade 3 or 4, and suspected to be related to the study drug.	Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 30 days, up to a maximum duration of approximately 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival is defined as the time from the start of study treatment to death due to any cause. OS was analyzed using the Kaplan-Meier method.	Up to approximately 7 years and 6 months.
Progression Free Survival (PFS) by Investigator Assessment Per RECIST 1.1	Progression free survival is defined as the time from the initiation of study treatment to disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier estimates.	Up to approximately 2 years and 9 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2016
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: June 16, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimated): July 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Neoplasms; Neuroendocrine Tumors; Adenoma, Islet Cell; MTOR Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Everolimus
• Other Study ID Numbers: CRAD001PCN31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No