Clinical Trial · NCT01860742

Randomized Phase III of PRRT Versus Interferon

Overview

The purpose of this study is to assess the benefit of 177Lu-DOTATATE versus interferon α-2b in patients with progressive, unresectable, non-pancreatic gastrointestinal neuroendocrine tumors resistant to therapy with somatostatin analogues, in terms of disease control.

Sponsor

Jules Bordet Institute

Phase

Phase 3

Contacts

Patrick Flamen, M.D., Ph.D. (PRINCIPAL_INVESTIGATOR)

Christophe Deroose, M.D., Ph.D. (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT01860742

Drug / Compound

DOTATATE

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

DOTATATE

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

Eligibility

Inclusion

Adequate bone marrow function with:
All necessary baseline procedures should be performed within 2 weeks prior to randomization date.
Total Bilirubin ≤ 2xULN;
Disease progression on a somatostatin receptor-imaging (PET/CT or SPECT/CT) over the last 12 months (apparition of new lesion(s) or increase in the transaxial plane diameter of more than 30% on the same imaging modality).
Adult patients (≥ 18 yrs).
Disease progression under SSAs (SSAs-resistant disease). Disease progression must be documented with at least one of the following:
There should be at least one target lesion. A target lesion should fulfill all the following criteria:
Transaminases (AST and ALT) ≤ 5xULN;
Radiological disease progression (according to RECIST 1.1) on an MRI or CT over the last 12 months.
Uptake higher than the physiological liver uptake on the baseline 68Ga-DOTATATE PET/CT
Serum albumin \> 3.0 g/dL with normal prothrombin time (\>70%) unless for patients under coumarin anticoagulation therapy.
Adequate liver function with:
Not previously irradiated.
Histology-proven non-pancreatic gastrointestinal NETs.
Adequate renal function with GFR ≥ 50 mL/min/1.73m2 (evaluated by 51Cr-EDTA test).
Platelet count ≥ 100·109/L.
ECOG Performance Status ≤ 1.
Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective form of contraception for the duration of study participation and up to six months after the end of the treatment. A pregnancy test (serum) must be performed within 2 weeks prior to inclusion for every female patient of childbearing potential and it must be negative.
Hemoglobin ≥ 9 g/dL;
Long-acting SSAs must be discontinued at least 4 weeks before the study treatment start date and, if needed, switched to short-acting analogues which must be stopped 48h before the treatment date.
Neutrophil ≥ 1.5·109/L;
Longest transaxial plane diameter ≥ 20mm measured on the CT or MRI;

Exclusion

Resectable tumor with curative intent.
Pregnant or lactating patients.
Treatment with interferon 12 months prior to inclusion in the study.
Previous PRRT or MIBG treatment.
Known autoimmune hepatitis.
Hypersensitivity to interferon α-2b or to any component of the product.
Patients with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator's opinion, may interfere with completion of the study.
Prior external beam radiotherapy on kidneys or on more than 25% of bone marrow.
Presence of non-benign 18FDG-positive lesions (higher than 2 x normal liver (or thoracic aorta uptake -SUVmax- in case of liver involvement)) without significant 68Ga-DOTATATE uptake.
Radiotherapy, chemotherapy, embolization, mammalian target of rapamycin (mTOR)-inhibitors, receptor tyrosine-kinase inhibitors or other investigational therapy within 12 weeks prior to inclusion in the study.
Patients with known uncontrolled brain metastases.
Diffuse bone marrow infiltration on the baseline 68Ga-DOTATATE PET/CT confirmed by MRI.
Patients after organ transplantation under immunosuppressive therapy.
Any major surgery within the last 6 weeks prior to inclusion in the study.
Uncontrolled congestive heart failure (NYHA stade ≥ 2).