A Phase 3, Prospective, Randomized, Double-blind, Multi-center Study of the Efficacy and Safety of Lanreotide Autogel®/Depot 120 mg Plus BSC vs. Placebo Plus BSC for Tumour Control in Subjects With Well Differentiated, Metastatic and/or Unresectable, Typical or Atypical, Lung Neuroendocrine Tumours
Overview
- Phase
- Phase 3
- Intervention
- Best Supportive Care
- Conditions
- Neuroendocrine Tumors in Lung
- Sponsor
- Ipsen
- Enrollment
- 77
- Locations
- 57
- Primary Endpoint
- Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of LAN plus BSC versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical bronchopulmonary NETs.
This study contains two phases: the Double-Blind (DB) Phase, and the Open Label (OL) Phase. The DB Phase includes: Screening, Baseline and Treatment period. The OL Phase will consist of two periods: Treatment Period and Follow-Up Period.
The primary objective will be to describe the antitumour efficacy of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) every 28 days, in terms of progression-free survival (PFS), measured by central review using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, in subjects randomized to LAN with unresectable and/or metastatic well differentiated, typical or atypical bronchopulmonary neuroendocrine tumours.
Recent updates of National Cancer Institute Cancer Network (NCCN) & European Neuroendocrine Tumor Society (ENETS) guidelines recommend SSA in first line for the treatment of locoregional unresectable or metastatic bronchopulmonary NETs as an option beyond 'observation' leading to slow and difficult recruitment in SPINET study. Consequently, it was decided to prematurely stop the recruitment in the SPINET study and to transition all subjects still treated in the double-blind phase to the open label (OL) treatment and follow-up phases following respective country approvals of Amendment #5.
The new aim of this Phase 3, multicenter, prospective, randomized placebo-controlled clinical study is to describe the antitumor efficacy and safety of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) in subjects with well-differentiated, metastatic and/or unresectable, typical or atypical, bronchopulmonary NETs.
Detailed Description
As planned initially, a total of 216 eligible patients with well-differentiated typical or atypical, metastatic and/or unresectable bronchopulmonary NETs, and a positive somatostatin receptor imaging (SRI) (Octreoscan® ≥ grade 2 Krenning scale; Ga-PET scan: uptake greater than liver background), were to be randomized 2:1 to either LAN plus BSC (120mg/28 days) or placebo plus BSC following the stratification of 1) typical versus atypical and 2) prior chemotherapy versus no prior chemotherapy\*. \* cytotoxic chemotherapy or molecular targeted therapy or interferon. At the time of the premature stop of the recruitment (as per Protocol Amendment #5), 77 patients were enrolled. All patients still treated in the DB Phase were entered into the OL Phase (either for Follow up or for OL treatment periods). The transition to the OL periods was done on a country-basis and per patient, at the following planned scheduled visit (i.e. approximately 28 days from the last injection). Patients enrolled into the study not progressing at the time of study stop, and who agree to stay on LAN therapy (i.e. OL Treatment Period) receive the study active treatment until evidence of disease progression (based on local radiological assessment then confirmed centrally), development of unacceptable toxicity, or premature withdrawal for any reason or up a maximum of 18 months after the last patient randomized. After disease progression patients are followed for survival, QoL and all subsequent anticancer treatments in the OL Follow-up period up to the end of the study (i.e up to 18 months after the last patient randomized).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have metastatic and/or unresectable pathologically confirmed well-differentiated, typical or atypical neuroendocrine tumor of the bronchopulmonary
- •Histologic evidence of Well differentiated Neuroendocrine tumors (NETs) of the bronchopulmonary (typical and atypical according to the World Health Organisation (WHO criteria), evaluated locally)
- •Has a mitotic index \<2 mitoses/2 mm2 for typical carcinoid (TC) and \<10 mitoses/2 mm2 and/or foci of necrosis for atypical carcinoid (AC)
- •At least one measurable lesion of the disease on imaging (CT or MRI; RECIST 1.1)
- •Positive Somatostatin receptors (SSTR) imaging
Exclusion Criteria
- •Poorly differentiated or high grade carcinoma, or patients with neuroendocrine tumors not of bronchopulmonary origin
- •Has been treated with a Somatostatin analog (SSA) at any time prior to randomization, except if that treatment was for less than 15 days (e.g. peri-operatively) of short acting SSA or one dose of long acting SSA and the treatment was received more than 6 weeks prior to randomization
- •Has been treated with Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization
- •Has been treated with more than two lines of cytotoxic chemotherapy or molecular targeted therapy or interferon for bronchopulmonary NET
Arms & Interventions
Placebo
120mg every 28 days until disease progression, death, or unacceptable toxicity during the double-blind phase. The patient may enter open-label phase for treatment with Lanreotide.
Intervention: Best Supportive Care
Lanreotide (Autogel formulation)
120mg every 28 days until disease progression, death, or unacceptable toxicity
Intervention: Lanreotide (Autogel formulation)
Lanreotide (Autogel formulation)
120mg every 28 days until disease progression, death, or unacceptable toxicity
Intervention: Best Supportive Care
Placebo
120mg every 28 days until disease progression, death, or unacceptable toxicity during the double-blind phase. The patient may enter open-label phase for treatment with Lanreotide.
Intervention: Placebo
Outcomes
Primary Outcomes
Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review
Time Frame: Up to a maximum of 33 months
PFS for subjects randomised in the lanreotide group, assessed by central review using Response Evaluation Criteria In Solid Tumours Version 1.1 (RECIST v1.1) criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during either the double-blind phase, or the open-label treatment phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.
Secondary Outcomes
- Time to Treatment Failure (TTF) in the Double-Blind Phase(Up to a maximum of 15 months)
- Objective Response Rate (ORR) in the Double-Blind Phase(Up to a maximum of 15 months)
- Median PFS Time in the Double-Blind Phase, Assessed by Central Review(Up to a maximum of 15 months)
- Median PFS Time in the Double-Blind Phase, Assessed by Local Review(Up to a maximum of 15 months)
- Percentage of Subjects With a Decrease of CgA ≥30% From Baseline at Week 8 in the Double-Blind Phase and Open-Label Treatment Phase(Baseline and Week 8 in the double-blind phase; Baseline and Week 8 in the open-label treatment phase)
- Mean Changes From Baseline in Urinary 5-hydroxyindoleacetic Acid (5-HIAA) Levels in the Double-Blind Phase and Open-Label Treatment Phase(Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months))
- Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase(Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months))
- Mean Changes From Baseline in Quality of Life (QoL), as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Global Health Status/QoL Score(Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months))
- Percentage of Subjects Who Experienced QoL Deterioration(Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months))