Clinical trial NCT01578239
Conditions: Carcinoid Tumor of the Small Bowel Neuroendocrine Tumour
Keywords: Neuroendocrine tumour 177Lu-Dota0-Tyr3-octreotate
Sponsor: Advanced Accelerator Applications
Start date: 2012-09-06; Completion date: 2021-01-18
Enrollment: 231 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III study comparing treatment with Lutathera plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in participants with metastasized or locally advanced, inoperable, somatostatin receptor positive, histologically proven midgut carcinoid tumours with progression despite LAR treatment.

Detailed description:
After the screening period, participants who signed the ICF and were eligible for the study in accordance with the entry criteria were randomly assigned to treatment either Lutathera or Octreotide LAR. Participant randomization was performed according to a centralized permuted block randomization scheme with a balanced ratio (1:1) between the 2 treatment groups, stratified by tumor uptake score and by the length of time that a participant was on a constant dose of Octreotide (=\< 6 versus \> 6 months).

Objective tumor assessment in both groups was performed every 12+/-1 weeks from the randomization date according to RECIST Criteria until progression was centrally confirmed:

1. Any participants with progressive disease (confirmed by central review of CT/MRI scans) ceased the treatment/assessment period and proceeded to the long-term follow-up period for evaluation of survival and long-term safety.
2. All non-progressive participants continued treatment/assessments until the PFS primary endpoint was met (i.e. 74 evaluable and centrally confirmed disease progressions or death events). Once the Primary End-Point was reached:

   1. Participants who received more than 76 weeks of treatment/assessment, stopped the study treatment (however somatostatin analogues could be received as subsequent treatment as per Investigator's discretion) but continued the long-term follow-up assessment for 5 years overall from the date of randomization of the last participant randomized.
   2. The remaining randomized participants continued in the fixed 76-week treatment/assessment period unless progression occurred, then continued the long-term follow-up assessments for 5 years overall from the date of randomization of the last participant.

Arms: arm 1: * 30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.
* Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).
* Concomitant amino acids were given with each administration for kidney protection.
* 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.
* In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed. arm 2: * 60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.
* In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Interventions: intervention 1: Octreotide LAR intervention 2: 177Lu-DOTA0-Tyr3-Octreotate
Intervention descriptions: intervention 1: In the experimental arm, 30 mg Octreotide LAR treatment was given to the participants until the end of study for symptom control purpose, unless the participant progressed or died.

In the active comparator arm, 60 mg Octreotide LAR treatment was given to the participants every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died. intervention 2: Four administrations of 7.4 GBq (200 mCi) 177Lu-DOTA0-Tyr3-Octreotate administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.

Protocol documents: