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Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumors (SPINET)

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ClinicalTrials.gov Identifier: NCT02683941
Recruitment Status : Active, not recruiting
First Posted : February 17, 2016
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

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 lung NETs.

This study contains two phases: the Double-Blind (DB) Phase, and the Open Label (OL) Extension Phase. The DB Phase includes: Screening, Baseline and Treatment period. The OL Extension Phase will consist of two periods: Treatment Period and Follow-Up Period.

The primary objective will be to compare the antitumour efficacy of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) every 28 days versus placebo plus BSC, 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 with unresectable and/or metastatic well differentiated, typical or atypical lung neuroendocrine tumours.

Recent updates of NCCN & ENETS guidelines recommend SSA in first line for the treatment of locoregional unresectable or metastatic lung NETs as an option beyond 'observation'. Consequently, it was decided to prematurely stop the recruitment in the SPINET study and to transition subjects still treated in the double-blind phase to the OL treatment phase following the country approval 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, lung NETs.


Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors in Lung Drug: Lanreotide (Autogel formulation) Drug: Placebo Phase 3

Detailed Description:

As planned initially, a total of 216 eligible patients with well-differentiated typical or atypical, metastatic and/or unresectable lung NETs, and a positive somatostatin receptor imaging (SRI) (Octreoscan® ≥ grade 2 Krenning scale; Ga-PET scan: uptake greater than liver background), had 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*. Due to the premature stop of the recruitment (as per Protocol Amendment #5), 77 patients have been enrolled. All patients still treated in the DB Phase have been entered into the OL Treatment Period (either for follow up or for OL treatment). The transition to the OL treatment period was done by country and per patient, at the following planned scheduled visit (i.e. approximately 28 days from the last injection). Patients enrolled into the study stay on LAN therapy (i.e. OL Treatment Period) until evidence of disease progression (assessed locally and confirmed centrally), development of unacceptable toxicity, or premature withdrawal for any reason or up to 18 months after the last patient randomised. After disease progression patients are followed for survival, QoL and all subsequent anticancer treatments up to the end of the study.

* cytotoxic chemotherapy or molecular targeted therapy or interferon.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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 Tumor Control in Subjects With Well Differentiated, Metastatic and/or Unresectable, Typical or Atypical, Lung Neuroendocrine Tumors
Actual Study Start Date : February 2016
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
Experimental: Lanreotide (Autogel formulation)
120mg every 28 days until disease progression
Drug: Lanreotide (Autogel formulation)
120mg every 28 days until disease progression
Other Names:
  • Lanreotide Depot
  • Somatuline

Placebo Comparator: Placebo
120mg every 28 days until disease progression, then patient may enter open-label treatment with Lanreotide
Drug: Placebo
Saline solution 0.9% administered via deep subcutaneous injection every 28 days until disease progression.




Primary Outcome Measures :
  1. Progression-Free Survival (PFS), for subjects randomized in LAN group, assessed by central review using RECIST v1.1 criteria [ Time Frame: From randomisation up to disease progression or up to 18 months (approximately) after the last patient is randomised. ]
    PFS measured by central review using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, defined as the time from randomization to disease progression or death from any causes


Secondary Outcome Measures :
  1. Progression-free survival (PFS), assessed by central review using RECIST v1.1 criteria every 12 weeks, [ Time Frame: From randomization to disease progression or death from any causes during the double-blind phase ]
  2. Progression-free survival (PFS), assessed by local review using RECIST v1.1 criteria every 12 weeks [ Time Frame: From randomization to disease progression or death from any causes during the double-blind phase ]
  3. ORR: objective response rate of CR or PR measured by RECIST v1.1 criteria every 12 weeks [ Time Frame: From randomisation up to the Post Treatment/Early Withdrawal Visit during the double-blind phase ]
  4. Time to treatment failure during the double-blind phase [ Time Frame: From randomisation up to event according to central review or to event according to local review whatever the one which occurs first ]
    Defined as the time from randomization to disease progression using RECIST v1.1, death, consent withdrawn, an AE, protocol deviations, lost to follow-up, the appearance of carcinoid syndrome or other hormone related syndrome necessitating the initiation of SSAs (rescue octreotide and/or LAR SSA), or initiation of anticancer treatment

  5. Mean changes from Baseline in the biomarker chromogranin A (CgA) [ Time Frame: Every 12 weeks thereafter until the post Double-Blind and in the Open Label Extension Treatment Phase ]
  6. Proportion of subjects with a decrease of CgA ≥30% at week 8 in the population of subjects with an elevated CgA (≥2 x ULN) at Baseline [ Time Frame: Double-blind and the Open-label treatment phases ]
  7. Change in Quality of Life (QoL), as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 [ Time Frame: Baseline, week 12, every 12 weeks and at the Post treatment/Early Withdrawal Visit and in the OL Extension Treatment and Follow-up phases ]
  8. Time to QoL deterioration, defined by a decrease from baseline in EORTC Quality of Life Questionnaire C30 (QLQ-C30) score of at least 10 points [ Time Frame: Double-blind, Open-label Treatment and Follow-up phases ]
  9. Mean changes from Baseline in urinary 5-HIAA levels in subjects with elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) (≥2 x Upper limit of normal range) at Baseline [ Time Frame: Every 12 weeks thereafter, and at the Post Treatment/Early Withdrawal Visit and in the Open-label Extension Treatment phase ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have metastatic and/or unresectable pathologically confirmed well-differentiated, typical or atypical neuroendocrine tumor of the lung
  • Histologic evidence of Well differentiated Neuroendocrine tumors (NETs) of the lung (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 lung origin are excluded
  • Has been treated with an Somatostatin analogs (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 Lung NET

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02683941


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Sponsors and Collaborators
Ipsen
Investigators
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Study Director: Ipsen Medical Director Ipsen

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Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02683941     History of Changes
Other Study ID Numbers: A-US-52030-328
2015-004992-62 ( EudraCT Number )
First Posted: February 17, 2016    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Lanreotide
Angiopeptin
Somatostatin
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs