177Lutetium-octreotate Treatment Prediction Using Multimodality Imaging in Refractory NETs (LUMEN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Jules Bordet Institute
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT01842165
First received: April 25, 2013
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to determine if 68Gallium-octreotate and 18Fluorodesoxyglucose uptake, apparent diffusion coefficient and post 177Lu-octreotate SPECT/CT dosimetry are reliable predictors for lesion-by-lesion treatment outcome.


Condition Intervention Phase
Gastroenteropancreatic Neuroendocrine Tumors
Drug: intravenous injection of 177Lu-octreotate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The LuMEn Trial: 177Lu-octreotate Treatment Outcome Prediction Using Multimodality Imaging in Refractory Neuroendocrine Tumours.

Resource links provided by NLM:


Further study details as provided by Jules Bordet Institute:

Primary Outcome Measures:
  • the difference in the diameter for each target lesion after each cycle of the treatment measured on MRI (or on CT scan if MRI is not applicable) [ Time Frame: 3 years [Anticipated] ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • RECIST 1.1 response [ Time Frame: 3 years [Anticipated] ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: 3 years [Anticipated] ] [ Designated as safety issue: No ]
  • Biochemical response (evolution of plasma chromogranin A levels). [ Time Frame: 3 years [Anticipated] ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: May 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
177Lu-octreotate therapy
an intravenous injection of 177Lu-octreotate with simultaneous infusion of an aminoacid solution will be performed in this one-arm monocentric study
Drug: intravenous injection of 177Lu-octreotate
an intravenous injection of 177Lu-octreotate with simultaneous infusion of an aminoacid solution will be performed
Other Names:
  • 177Lu-DOTATATE
  • Lutate

Detailed Description:

This is a feasibility study evaluating the use of 177Lutetium-octreotate in the treatment of advanced refractory Neuroendocrine Tumors.

Objectives of the study:

  1. primary (on a lesion basis): To assess the value of the following parameters (obtained through functional and molecular imaging) for predicting the lesion-by-lesion treatment outcome: 68Ga-octreotate and 18FDG uptake on PET/CT scans as well as apparent diffusion coefficient on diffusion-weighted magnetic resonance imaging (absolute values at baseline and after each cycle and their relative differences) and post 177Lu-octreotate SPECT/CT dosimetry after each cycle.
  2. secondary (on a patient basis): To generate a patient-based response model based on the aforementioned parameters.

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 amino acid 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 lesion-basis (change of longest transversal diameter).
  • on a patient-basis using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient-based

    • Age above 18 years.
    • Histology-proven advanced Gastroenteropancreatic-Neuroendocrine tumors.
    • Proven disease progression:(2 from the below criteria must be present)

      1. clinically: sustained (for more than 2 weeks) increase by 50% of NET-specific symptoms frequency (diarrhea or flushes), or of severity by 1 grade (according to CTCAE version 4.03),
      2. biochemically, by significant increase in tumoral markers (plasma Chromogranin A,
      3. radiologically, according to RECIST 1.1 criteria on a CT or MRI (over 1 year).
    • Disease refractory to somatostatine analogues and/or standard systemic therapy available in Belgium at the time of inclusion criteria.
    • Adequate renal function with GFR≥50 mL/min.
    • Adequate bone marrow function with Hemoglobin≥9 g/dL; WBC≥2000/μL; platelet count≥100000/μL.
    • Adequate liver function with bilirubin total ≤2 x upper limit of normal (ULN) and transaminases ≤5 x ULN., serum albumin>3,0gr/dL with normal prothrombin time (>70%).
    • Eastern Cooperative Oncology Group Performance Status ≤1.
    • Women of childbearing potential and men 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 serum pregnancy test will also be performed prior inclusion.
    • Patient's written informed consent obtained prior to any study procedure.
  2. Lesion-based: The patient must have at least one target lesion fulfilling all of the below criteria:

    • 68Ga-octreotate PET/CT (performed within a period of 3 weeks after signature of the informed consent form: tumoral uptake higher than the physiological liver uptake in a lesion with short-axis diameter superior to 15mm (measured on PET/CT),
    • at least one of these lesions morphologically measurable on the MRI with RECIST 1.1 (or CT if MRI is not applicable),
    • target lesion should not have been previously irradiated.

Exclusion Criteria:

  • Possible surgery with curative intent.
  • Surgery, radiotherapy, chemotherapy, within the last 6 weeks.
  • Diffuse bone marrow infiltration on 68Ga-octreotate PET/CT confirmed by MRI.
  • Patients with known uncontrolled brain metastases.
  • Short-acting somatostatin analogues not interrupted for 48 hours before or long-acting somatostatin not interrupted for at minimum of 4 weeks before therapy.
  • Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator's opinion, may interfere with completion of the study.
  • Pregnancy. Women of child-bearing potential refusing an adequate contraception.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01842165

Contacts
Contact: Patrick Flamen, M.D.,Ph.D. + 32-2-541 32 40 patrick.flamen@bordet.be
Contact: Ioannis Karfis, M.D. + 32-2-541 32 40 ioannis.karfis@bordet.be

Locations
Belgium
Jules Bordet Institute Recruiting
Brussels, Belgium, B-1000
Sponsors and Collaborators
Jules Bordet Institute
Investigators
Principal Investigator: Patrick Flamen, M.D., Ph.D. Jules Bordet Institute
Study Chair: Amélie Deleporte, MD Jules Bordet Institute
Study Chair: Alain Hendlisz, MD Jules Bordet Institute
Study Chair: Marc Lemort, MD, PHD Jules Bordet Institute
Study Chair: Patrick Emonts, MD Jules Bordet Institute
Study Chair: Godelieve Machiels, MD Jules Bordet Institute
Study Chair: Ioannis Karfis, MD Jules Bordet Institute
Study Chair: Bruno Vanderlinden, MSc Jules Bordet Institute
Study Chair: Zéna Wimana, MSc Jules Bordet Institute
Study Chair: Ghanem Ghanem, PharmD PhD Jules Bordet Institute
  More Information

No publications provided

Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT01842165     History of Changes
Other Study ID Numbers: IJBMNLUMEN, 2012-003666-41
Study First Received: April 25, 2013
Last Updated: March 10, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Jules Bordet Institute:
Peptide Receptor Radionuclide Therapy (PRRT)
Neuroendocrine Tumors

Additional relevant MeSH terms:
Neuroendocrine Tumors
Intestinal Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on September 16, 2014