Study to Assess the Efficacy and Safety of Lanreotide Autogel® in Chinese Participants With GEP-NETs (PALACE)

A Phase 3, Single-arm, Open-label, Multicentre Study to Assess the Efficacy and Safety of Deep Subcutaneous Injections of Lanreotide Autogel® 120 mg Administered Every 28 Days in Chinese Participants With Unresectable, Locally Advanced or Metastatic Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETs)

This study will be conducted to support the registration of the lanreotide Autogel 120 mg formulation in China for the treatment of GEP-NETs and treatment of clinical symptoms of NETs.

The study will include a screening period of up to 4 weeks followed by a 48-week intervention period. After completion of the main study period, five participants will continue in a self/partner injection cohort with lanreotide Autogel 120 mg every 28 days for 24 weeks.

Study Overview

• Status: Completed
• Conditions: Gastroenteropancreatic Neuroendocrine Tumor
• Intervention / Treatment: Drug: Lanreotide autogel

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Sciences
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin medical university cancer hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The first affiliated hospital of Zhengzhou university
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Affiliated to Fudan University
    • Shanghai, Shanghai, China, 200433
      • Fudan University Shanghai Cancer Centre
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310058
      • The First Affiliated Hospital of College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Capable of giving signed informed consent
• Male or female of 18 years of age or older when informed consent is obtained
• Has a histologically proven Grade 1 or 2 GEP-NET according to WHO (World Health Organisation) classification
• Has an unresectable metastatic or locally advanced NET.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 2.

Exclusion Criteria:

• Participants with poorly differentiated Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC), high-grade GEP-NEC and goblet cell carcinoid.
• Has been treated with octreotide acetate long-acting release or lanreotide acetate Autogel formulation within 8 weeks prior to screening tests or lanreotide PR 40 mg within 4 weeks prior to screening tests.
• Has been treated with subcutaneous or intravenous octreotide acetate within 1 week prior to screening tests.
• Has been treated with mammalian target of rapamycin (mTOR) inhibitors or multi-target tyrosine kinase (MTK) inhibitors within 4 weeks prior to screening tests.

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
Other: lanreotide Autogel 120 mg; Subjects will be treated with lanreotide Autogel® 120mg, every 28 days (+/- 3 days).	Drug: Lanreotide autogel; Administered as deep subcutaneous (SC) injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR) of Tumour Response Assessed by Blinded Independent Central Review (BICR) at Week 24	The CBR was defined as the percentage of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR), or continued stable disease (SD) until the time of assessment according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by BICR Within Weeks 24 and 48	The PFS was defined as the time from the first administration of study intervention to the date of the first documented PD measured using RECIST criteria v1.1 and confirmed by BICR, or death from any cause, whichever comes first. The PFS was estimated using the Kaplan-Meier method. The PD was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24 and 48
Overall Survival (OS) at the End of the Main Intervention Period	The OS was defined as the time from the first administration of study intervention to the date of death from any cause. The OS was estimated using the Kaplan-Meier method.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Week 48 (end of the main intervention period)
Time to Progression (TTP) During Main Intervention Period	The TTP was defined as the time from the first administration of study intervention to the date of the first documented PD, or clinical progression confirmed by the investigator. The TTP was assessed by BICR and estimated using the Kaplan-Meier method. The PD was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 12, 24, 36 and 48
Percentage of Participants Alive and Without Tumour Progressive at Weeks 24 and 48	Percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 24 and 48 weeks after first dose of study intervention were reported. The PFS was estimated using the Kaplan-Meier method. The PD was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24 and 48
Clinical Benefit Rate Assessed by BICR at Week 48	The CBR was defined as the percentage of participants with a best overall response of confirmed CR, confirmed PR, or continued SD until the time of assessment according to RECIST criteria v1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Week 48
Overall Response Rate (ORR) at Weeks 24 and 48	The ORR was defined as the percentage of participants with a best overall response of confirmed CR or confirmed PR. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24 and 48
Disease Control Rate (DCR) at Weeks 24 and 48	The DCR was defined as the percentage of participants with a best overall response of confirmed CR, confirmed PR or SD. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started.	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24 and 48
Number of Participants With Neuroendocrine Tumours (NET)-Related Clinical Symptoms at Weeks 24 and 48	The presence or absence of endocrine symptoms of NETs (example; flushing, diarrhoea, abdominal pain, weakness, heartburn, nausea, vomiting, sweating, tremor, palpitation, or erythema) were assessed by the investigator at screening. In participants with symptoms of NETs at screening, a baseline assessment of the symptoms experienced in the last 4 weeks was performed by questioning before study intervention administration at Day 1. These symptoms were recorded in the case report form and severity graded upon National Cancer Institute Common Terminology Criteria for Adverse Events. Where, Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death.	Weeks 24 and 48
Change From Baseline in Plasma Chromogranin A (CgA) at Weeks 12, 24, 36 and 48	The CgA determination was useful for staging, prognosis and follow up, since the serum concentration correlated to the tumour mass. Blood samples were collected to measure circulating CgA.	Baseline (within 28 days before start of study intervention) and Weeks 12, 24, 36 and 48
Change From Baseline in 5-Hydroxyindoleacetic Acid (5-HIAA) at Weeks 12, 24, 36 and 48	Urine samples were collected to measure 5-HIAA.	Baseline (within 28 days before start of study intervention) and Weeks 12, 24, 36 and 48
Change From Baseline in Quality of Life (QoL) Assessment at Weeks 12, 24, 36 and 48	The European Organization for Research and Treatment of Cancer QoL Questionnaire for Cancer participants contains 30 single items. For questions 1 to 28, score ranges from 1 to 4 where, 1= not at all, 2= a little, 3= quite a bit and 4= very much. Global health status/QoL contains questions 29 and 30 and score ranges from 1 to 7, where 1= very poor and 7= excellent. Total score ranges from 0 (poor) to 100 (excellent). Higher score indicates a high QoL.	Baseline (within 28 days before start of study intervention) and Weeks 12, 24, 36 and 48

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Actual): June 10, 2022
• Study Completion (Actual): January 13, 2023

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Intestinal Diseases; Pancreatic Diseases; Stomach Neoplasms; Pancreatic Neoplasms; Neuroendocrine Tumors; Intestinal Neoplasms; Antineoplastic Agents; Lanreotide
• Other Study ID Numbers: D-CN-52030-411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Where patient data can be anonymised, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available.
• IPD Sharing Time Frame: Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available.
• IPD Sharing Access Criteria: Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No