Clinical Trials /

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

NCT03972488

Description:

The aim of NETTER-2 is to determine if Lutathera in combination with long-acting octreotide prolongs PFS in GEP-NET patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients are eligible, as well as patients previously treated with SSAs in the absence of progression.

Related Conditions:
  • Digestive System Neuroendocrine Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET
  • Official Title: A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

Clinical Trial IDs

  • ORG STUDY ID: CAAA601A22301
  • NCT ID: NCT03972488

Conditions

  • Gastro-enteropancreatic Neuroendocrine Tumor

Interventions

DrugSynonymsArms
LutatheraLutathera plus long-acting octreotide
long-acting octreotideLutathera plus long-acting octreotide
high dose long-acting octreotidehigh dose long-acting octreotide

Purpose

The aim of NETTER-2 is to determine if Lutathera in combination with long-acting octreotide prolongs PFS in GEP-NET patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients are eligible, as well as patients previously treated with SSAs in the absence of progression.

Trial Arms

NameTypeDescriptionInterventions
Lutathera plus long-acting octreotideExperimental
  • Lutathera
  • long-acting octreotide
high dose long-acting octreotideActive Comparator
  • high dose long-acting octreotide

Eligibility Criteria

        Inclusion Criteria:

          -  Presence of metastasized or locally advanced, inoperable (curative intent)
             histologically proven, well differentiated Grade 2 or Grade 3 gastroenteropancreatic
             neuroendocrine (GEP-NET) tumor diagnosed within 6 months prior to screening.

          -  Ki67 index ≥10 and ≤ 55%

          -  Patients ≥ 15 years of age and a body weight of > 40 kg at screening

          -  Expression of somatostatin receptors on all target lesions documented by CT/MRI scans,
             assessed by the following somatostatin receptor imaging (SRI) modalities within 3
             months prior to randomization: [68Ga]-DOTA-TOC (e.g. Somakit-TOC) PET/CT imaging or
             [68Ga]-DOTA-TATE PET/CT imaging (e.g. NETSPOT) or Somatostatin Receptor scintigraphy
             (SRS) with 111In-pentetreotide (Octreoscan SPECT/CT).

          -  The tumor uptake observed in the target lesions must be > normal liver uptake observed
             on planar imaging.

          -  Karnofsky Performance Score (KPS) ≥ 60

          -  Presence of at least 1 measurable site of disease

          -  Patients who have provided a signed informed consent form to participate in the study,
             obtained prior to the start of any protocol related activities

        Exclusion Criteria:

          -  Creatinine clearance < 40 mL/min calculated by the Cockroft Gault method

          -  Hb concentration < 5.0 mmol/L (<8.0 g/dL); WBC < 2x10E9/L (2000/mm3); platelets <
             75x10E9/L (75x10E3/mm3)

          -  Total bilirubin > 3 x ULN

          -  Serum albumin < 3.0 g/dL unless prothrombin time is within the normal range

          -  Pregnancy or lactation

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, are not allowed to participate in this study UNLESS they are using
             highly effective methods of contraception throughout the study and for 6 months after
             study drug discontinuation

          -  Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the
             study.

          -  Documented RECIST progression to previous treatments for the current GEP-NET at any
             time prior to randomization

          -  Patients for whom in the opinion of the investigator other therapeutic options (eg
             chemo-, targeted therapy) are considered more appropriate than therapy offered in the
             study, based on patient and disease characteristics

          -  Any previous therapy with Interferons, Everolimus (mTOR-inhibitors), chemotherapy or
             other systemic therapies administered for more than 1 month and within 12 weeks prior
             to randomization in the study.

          -  Any previous radioembolization, chemoembolization and radiofrequency ablation

          -  Any surgery within 12 weeks prior to randomization in the study

          -  Known brain metastases, unless these metastases have been treated and stabilized for
             at least 24 weeks, prior to screening in the study. Patients with a history of brain
             metastases must have a head CT with contrast to document stable disease prior to
             randomization in the study.

          -  Uncontrolled congestive heart failure (NYHA II, III, IV). Patients with history of
             congestive heart failure who do not violate this exclusion criterion will undergo an
             evaluation of their cardiac ejection fraction prior to randomization, preferably via
             gated equilibrium radionuclide ventriculography. The results from an earlier
             assessment (not exceeding 30 days prior to randomization) may substitute the
             evaluation at the discretion of the Investigator, if no clinical worsening is noted.
             The patient's measured cardiac ejection fraction in these patients must be ≥40% before
             randomization.

          -  QTcF > 470 msec for females and QTcF > 450 msec for males or congenital long QT
             syndrome

          -  Uncontrolled diabetes mellitus as defined by a fasting blood glucose > 2 ULN

          -  Hyperkaleamia > 6.0 mmol/L (CTCAE Grade 3) which is not corrected prior to study
             enrolment

          -  Any patient receiving treatment with short-acting octreotide, which cannot be
             interrupted for 24 h before and 24 h after the administration of Lutathera, or any
             patient receiving treatment with SSAs (e.g. octreotide long-acting), which cannot be
             interrupted for at least 6 weeks before the administration of Lutathera, unless the
             tumor uptake on target lesions observed by study-permitted somatostatin receptor
             imaging (SRI) modalities during continued long-acting SSA treatment is greater than
             the liver uptake observed by planar imaging.

          -  Patients with any other significant medical, psychiatric, or surgical condition,
             currently uncontrolled by treatment, which may interfere with the completion of the
             study.

          -  Prior external beam radiation therapy to more than 25% of the bone marrow.

          -  Current spontaneous urinary incontinence

          -  Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in
             situ of the uterine cervix, unless definitively treated and proven no evidence of
             recurrence for 5 years

          -  Patient with known incompatibility to CT Scans with IV contrast due to allergic
             reaction or renal insufficiency. If such a patient can be imaged with MRI, then the
             patient would not be excluded.

          -  Patients with known intolerance or hypersensitivity to any somatostatin analogs

          -  Patients who have participated in any therapeutic clinical study/received any
             investigational agent within the last 30 days
      
Maximum Eligible Age:N/A
Minimum Eligible Age:15 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:through Week 72 until 99 PFS events are reached
Safety Issue:
Description:Time from randomization to the first line progression (centrally assessed according to RECIST 1.1)

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:week 16 ±1; week 24 ±1 and then every 12 ±1 weeks until Week 72
Safety Issue:
Description:Rate of complete and partial responses (CR, PR) (centrally assessed according to RECIST 1.1)
Measure:Time to Decline (TTD) global health status, diarrhea, fatigue, pain (EORTC QLQ-C30)
Time Frame:every 12 ± 1 week from first treatment date until the end of treatment
Safety Issue:
Description:TTD by 10 points from baseline in EORTC QLQ-C30 questionnaire: global health status (TTD)-diarrhea (TTD)-fatigue, (TTD)-pain (TTD)
Measure:Time to Decline (TTD) Total Health Status (EORTC QLQ-G.I.NET21)
Time Frame:every 12 ± 1 week from first treatment date until the end of treatment
Safety Issue:
Description:TTD by 10 points from baseline in total health status score as measured by EORTC QLQ-G.I.NET21 questionnaire
Measure:Disease Control Rate (DCR)
Time Frame:week 16 ±1; week 24 ±1 and then every 12 ±1 weeks until Week 72
Safety Issue:
Description:Rate of CR, PR and SD between the two treatment arms (centrally assessed according to RECIST 1.1)
Measure:Duration of Response (DOR)
Time Frame:week 16 ±1; week 24 ±1 and then every 12 ±1 weeks until Week 72
Safety Issue:
Description:time from initially meeting the criteria for response (CR or PR) until the time of progression according to RECIST 1.1
Measure:Rate of Adverse Events
Time Frame:Lutathera: within 2 weeks before infusion and 4 ± 1 weeks after infusion.
Safety Issue:
Description:Rate of adverse events between the two treatment arms (scored according to CTCAE grade)
Measure:Rate of laboratory toxicities
Time Frame:Lutathera: within 2 weeks before infusion and 4 ± 1 weeks after infusion.
Safety Issue:
Description:Rate of laboratory toxicities between the two treatment arms (scored according to CTCAE grade)
Measure:Time to death
Time Frame:up to 4 years from end of treatment of last patient
Safety Issue:
Description:time from randomization date until day of death due to any cause between the two treatment arms

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Advanced Accelerator Applications

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