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

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)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04852679

Acronym

PALACE

Enrollment

Registered

2021-04-21

Start date

2021-05-24

Completion date

2023-01-13

Last updated

2024-10-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastroenteropancreatic Neuroendocrine Tumor

Brief summary

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.

Interventions

DRUGLanreotide autogel

Administered as deep subcutaneous (SC) injections

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Clinical Benefit Rate (CBR) of Tumour Response Assessed by Blinded Independent Central Review (BICR) at Week 24	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 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.

Secondary

Measure	Time frame	Description
Overall Survival (OS) at the End of the Main Intervention Period	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Week 48 (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.
Time to Progression (TTP) During Main Intervention Period	RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 12, 24, 36 and 48	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.
Percentage of Participants Alive and Without Tumour Progressive at Weeks 24 and 48	RECIST assessments performed at baseline (within 28 days before start of study intervention) and 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.
Clinical Benefit Rate Assessed by BICR at Week 48	RECIST assessments performed at baseline (within 28 days before start of study intervention) and 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.
Overall Response Rate (ORR) at Weeks 24 and 48	RECIST assessments performed at baseline (within 28 days before start of study intervention) and 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.
Progression Free Survival (PFS) by BICR Within Weeks 24 and 48	RECIST assessments performed at baseline (within 28 days before start of study intervention) and 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.
Number of Participants With Neuroendocrine Tumours (NET)-Related Clinical Symptoms at Weeks 24 and 48	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.
Change From Baseline in Plasma Chromogranin A (CgA) at Weeks 12, 24, 36 and 48	Baseline (within 28 days before start of study intervention) and 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.
Change From Baseline in 5-Hydroxyindoleacetic Acid (5-HIAA) at Weeks 12, 24, 36 and 48	Baseline (within 28 days before start of study intervention) and Weeks 12, 24, 36 and 48	Urine samples were collected to measure 5-HIAA.
Change From Baseline in Quality of Life (QoL) Assessment at Weeks 12, 24, 36 and 48	Baseline (within 28 days before start of study intervention) and 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.
Disease Control Rate (DCR) at Weeks 24 and 48	RECIST assessments performed at baseline (within 28 days before start of study intervention) and 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.

Countries

China

Participant flow

Recruitment details

This Phase 3 single-arm, open-label study was conducted in chinese adult participants with unresectable, locally advanced or metastatic Grade 1 or 2 gastroenteropancreatic neuroendocrine tumours (GEP-NETs) at 14 investigational sites in China between 24 May 2021 and 13 January 2023.

Pre-assignment details

This study consisted of a screening period (up to 4 weeks), followed by a 48-week main intervention period and then a 24-week independent injection period. A total of 43 participants were treated in this study.

Participants by arm

Arm	Count
Lanreotide Autogel 120 mg All participants received a fixed dose of lanreotide autogel 120 mg SC injection every 28 days up to 48 weeks during the main intervention period. After completion of the main intervention period, eligible participants entered an independent injection period to receive lanreotide autogel 120 mg SC injection every 28 days for 24 weeks.	43
Total	43

Withdrawals & dropouts

Period	Reason	FG000
Independent Injection Period	Missed study visit	1
Main Intervention Period	Adverse Event	1
Main Intervention Period	Progressive Disease	16
Main Intervention Period	Refused study visit	1
Main Intervention Period	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Lanreotide Autogel 120 mg
Age, Continuous	51.8 years STANDARD_DEVIATION 9.2
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	43 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Sex: Female, Male Female	18 Participants
Sex: Female, Male Male	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 43	0 / 5
other Total, other adverse events	43 / 43	2 / 5
serious Total, serious adverse events	4 / 43	0 / 5

Outcome results

Primary

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.

Time frame: RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24