A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours (NETTER-1)
The purpose of this study is to
- compare Progression Free Survival (PFS) after treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, progressive (as determined by Response Evaluation Criteria in Solid Tumors [RECIST] Criteria), somatostatin receptor positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours).
- compare the Objective Response Rate (ORR) between the two study arms
- compare the Overall Survival (OS) between the two study arms
- compare the Time to Tumour Progression (TTP) between the two study arms
- evaluate the safety and tolerability of 177Lu-DOTA0-Tyr3-Octreotate
- evaluate the health related quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-G.I.NET21 questionnaire
- explore the correlation of toxicity outcomes and administered radiation doses corrected for body weight and body surface area
- explore the correlation of clinical efficacy outcomes with the levels of the biomarkers Chromogranin-A (CgA) in the serum and 5-Hydroxyindoleacetic acid (5-HIAA) in the urine
- evaluate dosimetry, pharmacokinetics (PK) and ECG in a subset of 20 patients
- explore the correlation of clinical efficacy outcomes with OctreoScan® tumour uptake score
- explore the correlation of clinical outcomes with serum levels of Alkaline Phosphatase (AP)
Carcinoid Tumor of the Small Bowel
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicentre, Stratified, Open, Randomized, Comparator-controlled, Parallel-group Phase III Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours|
- Progression Free survival (PFS) [ Time Frame: 12+/- 1 weeks ] [ Designated as safety issue: No ]
Primary efficacy endpoint is PFS as measured by objective tumour response, centrally assessed according to RECIST Criteria.
CT/MRI tumour assessment in both arms will be performed every 12±1 weeks from the first treatment date.
- Safety assessments (Adverse Events, laboratory parameters, cancer related symptoms, Physical Examination, Vital signs, Karnofsky Performance Status, ECG) [ Time Frame: 72 weeks (unless early termination) : All adverse events (AEs) and serious adverse events (SAEs) will be recorded starting from the signing of the informed consent until the last study-related visit in both study arms. ] [ Designated as safety issue: Yes ]
The following parameters will be monitored:
- Changes from Baseline in Hematology (WBC, platelets, haemoglobin, MCV), Blood chemistry (BUN, serum creatinine and creatinine clearance, uric acid, albumin, total bilirubin, AP, aspartate aminotransferase [AST/ASAT], alanine aminotransferase [ALT/ALAT], gamma-glutamyl transferase [γ-GT], [Na], [K], lactic dehydrogenase [LDH], glycosylated hemoglobin/hemoglobin A1c [glycoHb], free thyroxine [fT4]) and Urinalysis (RBC/hpf, WBC/hpf, casts/lpf, protein, 5-HIAA),
- Cancer related symptoms,
- Physical Examination, including heart rate, blood pressure and weight,
- Karnofsky Performance Status,
- ECG intervals.
All AEs and SAEs reported (spontaneously or not) by the patient will be collected during the study.
- Long-term safety and efficacy assessment [ Time Frame: Every 6 months for a period of up to 3 years after the end of the study ] [ Designated as safety issue: Yes ]Patient will be contacted every 6 months up to 3 years after the end of the study (phone contacts or visits at Site). Laboratory assessments (haematology, biochemistry, urinalysis), SAEs suspected in relationship to the study drug, progression free survival (local evaluation) and overall survival data will be reported.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Other Name: SANDOSTATIN LARDrug: 177Lu-DOTA0-Tyr3-Octreotate
Four administrations of 7.4 GBq (200 mCi) 177Lu-DOTA0-Tyr3-Octreotate will be administered at 8±1-week intervals, which can be extended up to 16 weeks to accommodate resolving acute toxicity;
Active Comparator: Octreotide LAR
60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the patient progresses or dies (see Dose Modifying Toxicity (DMT);
Other Name: SANDOSTATIN LAR
A multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III study. In this study, treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) will be compared to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, somatostatin receptor positive, histologically proven midgut carcinoid tumours; these patients should be progressive under Octreotide LAR. In case patients in either arm experience clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections are allowed.
Objective tumour response in both arms will be assessed every 12±1 weeks from the first treatment date according to RECIST Criteria. The baseline CT scan/MRI must not be older than 4 weeks before the projected randomization date.
Patients will be evaluated for safety and tolerability in accordance with the Visit Schedules for the 177Lu-DOTA0-Tyr3-Octreotate arm and the Octreotide LAR arm as indicated in Table 1 and Table 2, respectively.
|Contact: Maurizio F Mariani, M.D||+39 0125 561 ext email@example.com|
|Contact: Paola Santoro, Biologist||+39 0125 561 ext firstname.lastname@example.org|
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|Study Director:||Paola Santoro, Biologist||Advanced Accelerator Applications|