Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET (NETTER-2)
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|ClinicalTrials.gov Identifier: NCT03972488|
Recruitment Status : Active, not recruiting
First Posted : June 3, 2019
Last Update Posted : October 5, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Gastro-enteropancreatic Neuroendocrine Tumor||Drug: Lutathera Drug: long-acting octreotide Drug: high dose long-acting octreotide Other: Optional post-progression re-treatment with Lutathera Other: Optional post-progression cross-over to Lutathera||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||222 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 22, 2020|
|Estimated Primary Completion Date :||November 30, 2023|
|Estimated Study Completion Date :||July 30, 2027|
|Experimental: Lutathera plus long-acting octreotide||
7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 weeks
Drug: long-acting octreotide
30 mg every 8 weeks during Lutathera treatment and every 4 weeks after last Lutathera treatment
Other: Optional post-progression re-treatment with Lutathera
additional 2-4 cycles of Lutathera (7.4 GBq/200 mCi x 4 cycles)
|Active Comparator: high dose long-acting octreotide||
Drug: high dose long-acting octreotide
60 mg every 4 weeks
Other: Optional post-progression cross-over to Lutathera
maximum 4 cycles of Lutathera (7.4 GBq/200 mCi x 4 cycles) plus octreotide long-acting (30 mg every 8 weeks)
- Progression Free Survival (PFS) [ Time Frame: through Week 72 until 99 PFS events are reached ]Time from randomization to the first line progression (centrally assessed according to RECIST 1.1 or death due to any cause)
- Objective Response Rate [ Time Frame: week 16 ±1; week 24 ±1 and then every 12 ±1 weeks until Week 72 ]Rate of complete and partial responses (CR, PR) (centrally assessed according to RECIST 1.1)
- 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 ]TTD by 10 points from baseline in EORTC QLQ-C30 questionnaire: global health status (TTD)-diarrhea (TTD)-fatigue, (TTD)-pain (TTD)
- 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 ]TTD by 10 points from baseline in total health status score as measured by EORTC QLQ-G.I.NET21 questionnaire
- Disease Control Rate (DCR) [ Time Frame: week 16 ±1; week 24 ±1 and then every 12 ±1 weeks until Week 72 ]Rate of CR, PR and SD between the two treatment arms (centrally assessed according to RECIST 1.1)
- Duration of Response (DOR) [ Time Frame: week 16 ±1; week 24 ±1 and then every 12 ±1 weeks until Week 72 ]Time from initially meeting the criteria for response (CR or PR) until the time of progression according to RECIST 1.1 or death due to underlying disease
- Rate of Adverse Events [ Time Frame: Lutathera: within 2 weeks before infusion and 4 ± 1 weeks after infusion. ]Rate of adverse events between the two treatment arms (scored according to CTCAE grade)
- Rate of laboratory toxicities [ Time Frame: Lutathera: within 2 weeks before infusion and 4 ± 1 weeks after infusion. ]Rate of laboratory toxicities between the two treatment arms (scored according to CTCAE grade)
- Time to death [ Time Frame: up to 4 years from randomization of last patient ]time from randomization date until day of death due to any cause between the two treatment arms
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||15 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 any of the following somatostatin receptor imaging (SRI) modalities within 3 months prior to randomization: [68Ga]-DOTA-TOC (e.g. Somakit-TOC®) PET/CT (or MRI when applicable based on target lesions) imaging, [68Ga]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging (e.g. NETSPOT®), Somatostatin Receptor scintigraphy (SRS) with [111In]-pentetreotide (Octreoscan® SPECT/CT), SRS with [99mTc]-Tektrotyd, [64Cu]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging.
- The tumor uptake observed in the target lesions must be > normal liver uptake.
- 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
- 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 treatment period (including cross-over and re-treatment, if applicable) 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 for GEP-NET administered for more than 1 month or within 12 weeks prior to randomization in the study.
- Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET
- 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 or MRI 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 via echocardiography. 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 hemoglobin A1c value > 7.5%
- 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.
- 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.
- Hypersensitivity to any somatostatin analogues, the IMPs active substance or to any of the excipients.
- Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days
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): NCT03972488
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|
|Responsible Party:||Advanced Accelerator Applications|
|Other Study ID Numbers:||
2019-001562-15 ( EudraCT Number )
|First Posted:||June 3, 2019 Key Record Dates|
|Last Update Posted:||October 5, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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