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Carcinoid Tumors After Failure of Somatostatin Analogs: a Randomized Phase III of Octreotide Lutate Peptid Receptor Radionuclide Therapy (PRRT) Versus Interferon α-2b

Phase 3
18 Years
Not Enrolling
Gastro-intestinal Neuroendocrine Tumors

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Trial Information

Carcinoid Tumors After Failure of Somatostatin Analogs: a Randomized Phase III of Octreotide Lutate Peptid Receptor Radionuclide Therapy (PRRT) Versus Interferon α-2b

This is a phase III study of Peptid Receptor Radionuclide Therapy (PRRT) with
177Lu-octreotate versus Interferon α-2b.

Objectives of the study:

1. To assess the benefit of 177Lu-octreotate versus interferon α-2b in patients with
progressive, unresectable,non-pancreatic gastrointestinal neuroendocrine tumors,
resistant to therapy with somatostatine analogues.

2. To assess efficacy and safety parameters of both treatment arms and the prognostic
value of tumor 68Ga-octreotate PET/CT and 18FDG PET/CT uptake at baseline, at mid and
end of PRRT treatment.

In the interferon arm: 5000000 Units of interferon will be administered subcutaneously
preferentially in the evening every second day.

In the 177Lu-octreotate arm: Treatment will consist of 177Lu-octreotate infusions in fixed
activities of 7,4 GigaBecqurel each, given 8-11 weeks apart, injected intravenously with
simultaneous infusion of an amino acid solution. (Before amino acid nephroprotection
solution, ondansetron, methylprednisolone and metoclopramid, are given intravenously in
order to prevent nausea or vomiting). Approximately 30 min after the beginning of the
aminoacid solution, 177Lu-octreotate is co-infused over 15-30 minutes. The amino acid
infusion is continued at the same rate for 3-5 more hours (total infusion lasts 4-6 hours).

In total, 4 cycles are planned. However, the total number of administered cycles will be
limited by critical organ (kidneys and bone marrow) cumulated absorbed doses.

Treatment efficacy will be assessed on a patient-basis by evaluation of the Progression-Free

Inclusion Criteria:

- Adult patients (> 18 yrs).

- Histology-proven non-pancreatic gastrointestinal neuroendocrine tumors.

- somatostatin analogue-resistant disease. Disease progression must be documented with
at least one of the following:

1. Radiological progression (according to RECIST 1.1) on an MRI or CT over the last
6 months.

2. Progression on a somatostatin receptor-imaging, PET/CT or SPECT/CT over the last
6 months [apparition of new lesion(s) or increase in the transaxial axis size of
more than 30% on the same imaging modality].

- On the baseline 68Ga-octreotate PET/CT: tumoral uptake higher than the physiological
liver uptake in all target lesions. A target lesion on the 68Ga-octreotate PET/CT
should fulfill the following criteria:

1. short-axis diameter superior to 15mm;

2. morphologically measurable on the CT or MRI with RECIST 1.1;

3. not previously irradiated.

- Adequate renal function with GFR≥50 mL/min/1.73m2 (evaluated by 51Cr-EDTA test)

- Adequate bone marrow function with:

1. Hemoglobin ≥9 g/dL;

2. Neutrophil ≥1,5•103/μL;

3. Platelet count ≥100•103/μL.

- Adequate liver function with:

1. Total Bilirubin ≤2x upper limit of normal (ULN);

2. Transaminases ≤5xULN;

3. Serum albumin >3,0 g/dL with normal prothrombin time (>70%) unless for patients
under coumadin anticoagulation therapy.

- Eastern Cooperative Oncology Group Performance Status ≤1.

- Women of childbearing potential and men must agree to use an effective form of
contraception for the duration of study participation and up to six months after the
end of the treatment. A serum pregnancy test will also be performed prior inclusion.

- Patient's written informed consent obtained prior to any study procedure.

Exclusion Criteria:

- Resectable disease with curative intent at enrollment time.

- Any major surgery within the last 6 weeks.

- Presence of non-benign 18FDG-positive lesions without 68Gallium-octreotate
significant uptake.

- Uncontrolled congestive heart failure (NYHA stade≥2 ).

- Impossibility to interrupt the short acting somatostatin analogues injections during
48 hours before and 24 hours after each PRRT injection.

- Diffuse bone marrow infiltration.

- Patients with known uncontrolled brain metastases .

- PRRT or MIBG at any time prior to enrollment in the study.

- Prior treatment with interferon.

- Prior external beam radiotherapy on kidneys or on more than 25% of bone marrow.

- History of other active malignant disease or clinical remission less than 5 years
(except in case of non melanoma skin cancer or in situ cervical carcinoma).

- Known autoimmune hepatitis.

- Patients after organ transplantation under immunosuppressive therapy.

- Subjects 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.

- Hypersensitivity or medical contraindication to interferon alpha or any component of
the product.

- Pregnancy, lactation. Women of child-bearing potential refusing an adequate

- Patients who have not provided a signed informed consent form to participate in the
study, obtained prior to the start of any protocol related activities.

- Urinary incontinence.

- Targeted surgery, radiotherapy (external beam), chemotherapy, embolization,
interferons, mammalian target of rapamycin (mTOR)-inhibitors or other investigational
therapy within 12 weeks prior to enrollment in the study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival

Outcome Time Frame:

3 years [Anticipated]

Safety Issue:


Principal Investigator

Patrick Flamen, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jules Bordet Institute


Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:




Start Date:

October 2013

Completion Date:

October 2016

Related Keywords:

  • Gastro-intestinal Neuroendocrine Tumors
  • Peptide Receptor Radionuclide Therapy (PRRT)
  • Neuroendocrine Tumors
  • Interferon alpha
  • Neuroendocrine Tumors