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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Jules Bordet Institute
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT01842165
First received: April 25, 2013
Last updated: April 4, 2016
Last verified: March 2016
  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 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The LuMEn Study: 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 time to progression (TTP) for each target lesion assessed on MRI (or on CT scan if MRI is not possible). [ Time Frame: 4 years [Anticipated] ] [ Designated as safety issue: No ]
    TTP is defined as the time between treatment initiation and objective tumor progression with censoring of patients who die as a result of any cause.


Secondary Outcome Measures:
  • Best morphological response according to RECIST 1.1 [ Time Frame: 4 years [Anticipated] ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: 4 years [Anticipated] ] [ Designated as safety issue: No ]
    PFS is defined as the time between treatment initiation and the first of the following events: disease progression (clinical or radiological) or death resulting from any cause.

  • Biochemical response (evolution of NET-specific tumoral uptake). [ Time Frame: 4 years [Anticipated] ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • The time to progression (TTP) for each target lesion assessed on MRI (or on CT scan if MRI is not applicable). [ Time Frame: 4 years [Anticipated] ] [ Designated as safety issue: No ]

Estimated Enrollment: 39
Study Start Date: May 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
177Lu-octreotate therapy
Treatment will consist of 177Lu-octreotate injections in fixed activities of 7,4 GBq (200 mCi) (±5%) each, given 12 weeks (±1 week) apart, injected intravenously simultaneously with nephroprotective perfusion of an amino acid solution.
Drug: Intravenous injection of 177Lu-octreotate
Treatment will consist of 177Lu-octreotate injections in fixed activities of 7,4 GBq (200 mCi) (±5%) each, given 12 weeks (±1 week) apart, injected intravenously simultaneously with nephroprotective perfusion of an amino acid solution.
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 PRRT treatment outcome:

    • 18FDG uptake on 18FDG PET/CT
    • 68Ga-octreotate uptake on 68Ga-octreotate PET/CT
    • Apparent diffusion coefficient on diffusion weighted MRI (for these 3 parameters, absolute values at baseline)
    • Tumor dosimetry on post 177Lu-octreotate SPECT/CT after each cycle.
  2. Secondary (on a patient basis): To generate a patient-based response model based on the previously defined parameters.
  3. Exploratory (on a lesion basis): To assess the value of the parameters mentioned in the primary objective for predicting the lesion-by-lesion PRRT treatment outcome:

    • absolute values of the three imaging parameters and their relative changes after each cycle;
    • serial tumor dosimetry on post-177Lu-octreotate SPECT/CT after each cycle.

Treatment will consist of 177Lu-octreotate injections in fixed activities of 7,4 GigaBecqurel each, given 11-13 weeks apart, injected intravenously with simultaneous infusion of an amino acid solution. (Before amino acid nephroprotection, 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 (= injections of 177Lu-octreotate) are planned. However, the total number of administered cycles will be limited by critical organ (kidneys and bone marrow) threshold toxicities.

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   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patient-based:

  1. Age above or equal to 18 years.
  2. Histology-proven advanced GEP-NETs.
  3. Disease progression defined as follows (at least one of the following):

    - Radiological disease progression (according to RECIST 1.1) on an MRI or CT over the last 12 months Or

    - 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] Or

    - Both of the following criteria (a+b):

    1. clinical progression:

      • sustained (for more than 2 weeks) increase of NET-specific hormonal hypersecretion related symptom frequency by 50% or,
      • sustained (for more than 2 weeks) increase of severity by 1 grade (according to NCI-CTCAE version 4.03).
    2. biochemical progression: by increase of NET-specific tumor markers (plasma Chromogranin A, plasma NSE, urine 5-HIAA or other) in two successive measurements.
  4. Disease refractory to SSA's and/or standard systemic therapy available in Belgium at the time of inclusion criteria.
  5. Long-acting SSAs should be discontinued at least 4 weeks before study treatment start date and, if needed, switched to short-acting analogues which should be stopped 48h before the treatment date.
  6. Adequate renal function with GFR ≥ 50 mL/min/1.73m2 (evaluated by 51Cr-EDTA test).
  7. Adequate bone marrow function with hemoglobin ≥ 9 g/dL; neutrophil ≥ 1.5·103/μL; platelet count ≥ 100·103/μL.
  8. Adequate liver function with total bilirubin ≤ 2 x ULN and transaminases ≤ 5 x ULN, serum albumin > 3 g/dL with normal prothrombin time (> 70%).
  9. ECOG Performance Status ≤ 1.
  10. 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 4 weeks prior to inclusion for every female patient of childbearing potential and it must be negative.
  11. Patient's written informed consent obtained prior to any study procedure.
  12. All necessary baseline procedures should be performed within 4 weeks prior to first 177Lu-octreotate injection (D0).

    Lesion-based:

  13. The patient must have at least one target lesion fulfilling all of the below criteria:

    • On the 68Ga-octreotate PET/CT: tumor uptake higher than the physiological liver uptake (grade III or IV of the Rotterdam visual score) in a lesion with longest transaxial plane diameter ≥20mm (measured on the CT, part of the PET/CT);
    • At least one of these lesions morphologically measurable according to RECIST 1.1 and progressive on the MRI (or CT if MRI is not applicable);
    • Target lesion should not have been previously irradiated.

Exclusion Criteria:

  1. Resectable tumor with curative intent.
  2. Any major surgery within the last 6 weeks prior to inclusion in the study
  3. Radiotherapy, chemotherapy, embolization, mammalian target of rapamycin (mTOR)-inhibitors, receptor tyrosine-kinase inhibitors, interferon, or other investigational therapy within the last 12 weeks prior to inclusion in the study.
  4. Diffuse bone marrow infiltration on the baseline 68Ga-octreotate PET/CT confirmed by MRI.
  5. Prior external beam radiotherapy on kidneys or on more than 25% of bone marrow.
  6. Patients with known uncontrolled brain metastases.
  7. 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.
  8. Pregnant or lactating patients.
  9. Women of childbearing potential and men with partners 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
Study Chair: Patrick Flamen, M.D., Ph.D. Jules Bordet Institute
Principal Investigator: Amélie Deleporte, MD Jules Bordet Institute
Principal Investigator: Alain Hendlisz, MD Jules Bordet Institute
Study Chair: Ioannis Karfis, MD Jules Bordet Institute
  More Information

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: April 4, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Federal Agency of Nuclear Control
Individual Participant Data  
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Intestinal Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
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
Octreotide
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 22, 2016