Randomized Interval Assessment Trial of Lu177-Dotatate in Slowly Progressive G1-2 Advanced Midgut Neuroendocrine Tumors

ConditionGrade1-2 Advanced Midgut Neuroendocrine Tumors (NETs)

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age18+

SponsorGrupo Espanol de Tumores Neuroendocrinos

About this trial

This is a randomized Phase II/late phase I de-escalation clinical trial with approved investigational medicinal products in new use condition, low intervention.

Disease under study Patients with unresectable or metastatic, slowly progressive, well-differentiated (Grade1 and Grade2), somatostatin receptor-positive midgut neuroendocrine tumors (GEP-NETs).

It is planned to randomize 166 patients with a histologically confirmed diagnosis of slowly progressive grade 1 or grade 2 advanced midgut neuroendocrine tumors (NETs) candidates to receive 177Lu-Dotatate targeted radioligand therapy (RLT). Patients are required to have SSTR+ disease, as evidenced on somatostatin receptor imaging. Patients will be randomized into two arms:

1. control arm: regimen 177Lu-Dotatate every 8 weeks (q8w) 2. experimental arm: regimen 177Lu-Dotatate every 16 weeks (q16w)

Research hypothesis: Less intensive somatostatin-receptor (SST) targeted radioligand therapy (RLT) (7.4 GBq/cycle 177Lu-Dotatate every 16 weeks x 4 cycles) is associated with less severe hematological toxicities and may mitigate the risk to develop therapy-related myeloid neoplasms (t-MN) with similar antitumor efficacy in slowly growing gastrointestinal grade 1-2 NETs.

Eligibility criteria

Qualifiers

Patients who have histologically confirmed diagnosis of unresectable, advanced or metastatic midgut NETs (originated in the jejunum-ileum or right colon) who are candidates to receive 177Lu-Dotatate targeted radioligand therapy (RLT) and SSA. Patients with a large SRI+ mesenteric mass with abdominal-dominant disease judged by the investigator to be a midgut NET will also be eligible.

Ki-67 index ≤ 20%.

Disease progression per RECIST v1.1 within 36 months prior to study entry,

Patients may be treatment naïve (first-line) or have received prior systemic therapy except for any type of prior RLT (not restricted to 177Lu-Dotatate).

Disqualifiers

Patients who have known hypersensitivity to lutetium-177 (177Lu), oxodotreotide, DOTA, somatostatin analogues, lysine, arginine, or any excipient/derivative of these agents

Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow

Prior whole liver internal radiation therapy (SIRT)

Prior radioligand therapy (RLT) (not restricted to 177Lu-Dotatate).

Trial design

Treatments tested in this trial

177Lu-Dotatate (7.4 Gigabecquerel/cycle) during 30 min intravenous infusion every 16 weeks (q8w) x 4 cycles; 2) and 3) as in the experimental arm.
177Lu-Dotatate (7.4 Gigabecquerel/cycle) during 30 min intravenous infusion every 8 weeks (q8w) x 4 cycles; 2) and 3) as in the experimental arm.
Amino acid solution
Lanreotide (Autogel formulation) or Octreotide LAR