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

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ClinicalTrials.gov Identifier: NCT01842165
Recruitment Status : Recruiting
First Posted : April 29, 2013
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute

Tracking Information
First Submitted Date  ICMJE April 25, 2013
First Posted Date  ICMJE April 29, 2013
Last Update Posted Date November 27, 2018
Study Start Date  ICMJE May 2013
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2016)
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] ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 25, 2013)
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] ]
Change History Complete list of historical versions of study NCT01842165 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2016)
  • Best morphological response according to RECIST 1.1 [ Time Frame: 4 years [Anticipated] ]
  • Progression Free Survival [ Time Frame: 4 years [Anticipated] ]
    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] ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2013)
  • RECIST 1.1 response [ Time Frame: 3 years [Anticipated] ]
  • Progression Free Survival [ Time Frame: 3 years [Anticipated] ]
  • Biochemical response (evolution of plasma chromogranin A levels). [ Time Frame: 3 years [Anticipated] ]
Current Other Pre-specified Outcome Measures
 (submitted: April 4, 2016)
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] ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 177Lutetium-octreotate Treatment Prediction Using Multimodality Imaging in Refractory NETs
Official Title  ICMJE The LuMEn Study: 177Lu-octreotate Treatment Outcome Prediction Using Multimodality Imaging in Refractory Neuroendocrine Tumours.
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastroenteropancreatic Neuroendocrine Tumors
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Intravenous injection of 177Lu-octreotate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 4, 2016)
39
Original Estimated Enrollment  ICMJE
 (submitted: April 25, 2013)
40
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01842165
Other Study ID Numbers  ICMJE IJBMNLUMEN
2012-003666-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jules Bordet Institute
Study Sponsor  ICMJE Jules Bordet Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Jules Bordet Institute
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP