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Trial record 15 of 50 for:    Peptide Receptor | Neuroendocrine Tumors

Randomized Phase III of PRRT Versus Interferon (CASTOR)

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ClinicalTrials.gov Identifier: NCT01860742
Recruitment Status : Withdrawn
First Posted : May 23, 2013
Last Update Posted : April 5, 2016
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastro-intestinal Neuroendocrine Tumors Drug: Interferon alpha-2b Drug: 177Lu-DOTATATE Phase 3

Detailed Description:

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

Objectives of the study:

  1. 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.
  2. To assess efficacy and safety parameters of both treatment arms and the predictive value of tumor 68Ga-DOTATATE PET/CT and 18FDG PET/CT uptake at baseline, at mid (+/- 16th week) and end (+/- 32th week) of treatment in both arms.

In the interferon arm: 5000000 Units of interferon will be administered subcutaneously preferentially in the evening three times a week (every other day) until disease progression.

In the 177Lu-octreotate arm: Treatment will consist of 177Lu-DOTATATE intravenous injections fractionated in fixed activities of 7,4 GigaBecquerel (200mCi) (+/- 5%), given every 8 (+/- 1) weeks with simultaneous nephroprotective infusion of an amino acid solution. (Before amino acid nephroprotection solution, ondansetron, methylprednisolone and metoclopramid, are given in infusions in order to prevent nausea or vomiting). Approximately 30 min after the beginning of the aminoacid solution, 177Lu-octreotate is injected via a second side-line over 15-30 minutes. The amino acid infusion is continued at the same rate until end (total infusion time: 4-6 hours).

In total, 4 injections of 177Lu-DOTATATE are planned. However, in respect of the absorded dose limits of critical organs(kidneys and bone marrow), the 4th 177Lu-DOTATATE injection will be tailored with a minimal administered activity of 4,6 GigaBecquerel.

Treatment efficacy will be assessed on a patient-basis using RECIST 1.1 and by Progression Free Survival. The value of tumor 68Ga-DOTATATE PET/CT and 18FDG PET/CT uptake as predicting imaging biomarkers will also be assessed in both arms.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Carcinoid Tumors After Failure of Somatostatin Analogs: a Randomized Phase III of Octreotide Lutate Peptid Receptor Radionuclide Therapy (PRRT) Versus Interferon α-2b
Study Start Date : December 2014
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : October 2016


Arm Intervention/treatment
Active Comparator: Interferon alpha-2b
Interferon α-2b in a dose of 5000000 Units administered subcutaneously every second day until progression or unacceptable adverse event from a clinical or a patient point of view.
Drug: Interferon alpha-2b
Interferon α-2b in a dose of 5000000 Units administered subcutaneously every second day
Other Name: Intron A

Active Comparator: 177Lu-DOTATATE
intravenous injection of 177Lu-octreotate with simultaneous infusion of an aminoacid solution
Drug: 177Lu-DOTATATE
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
Other Names:
  • 177Lu-octreotate
  • Lutate




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 3 years [Anticipated] ]

    PFS is defined by the time between treatment initiation and the first of the following events:

    • Disease progression according to RECIST 1.1;
    • Death of the patient from any cause;
    • Appearance of confirmed new lesion(s) on 68Ga-DOTATATE PET/CT or 18FDG PET/CT.


Secondary Outcome Measures :
  1. Treatment response according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) [ Time Frame: 3 years [Anticipated] ]
  2. Adverse events according to Common Terminology Criteria for Adverse Events version 4.03 (CTC 4.03-WHO criteria) [ Time Frame: 3 years [Anticipated] ]
  3. Tumor 18FDG PET/CT and 68Ga-octreotate PET/CT uptake at baseline, at mid and end of treatment [ Time Frame: 3 years [Anticipated] ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patients (≥ 18 yrs).
  2. Histology-proven non-pancreatic gastrointestinal NETs.
  3. Disease progression under SSAs (SSAs-resistant disease). Disease progression must be documented with at least one of the following:

    • Radiological disease progression (according to RECIST 1.1) on an MRI or CT over the last 12 months.
    • 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).
  4. There should be at least one target lesion. A target lesion should fulfill all the following criteria:

    • Uptake higher than the physiological liver uptake on the baseline 68Ga-DOTATATE PET/CT
    • Longest transaxial plane diameter ≥ 20mm measured on the CT or MRI;
    • Not previously irradiated.
  5. 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.
  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 ≥ 1.5·109/L;
    • Platelet count ≥ 100·109/L.
  8. Adequate liver function with:

    • Total Bilirubin ≤ 2xULN;
    • Transaminases (AST and ALT) ≤ 5xULN;
    • Serum albumin > 3.0 g/dL with normal prothrombin time (>70%) unless for patients under coumarin anticoagulation therapy.
  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 2 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 specific procedure.
  12. All necessary baseline procedures should be performed within 2 weeks prior to randomization date.

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 or other investigational therapy within 12 weeks prior to inclusion in the study.
  4. Previous PRRT or MIBG treatment.
  5. Treatment with interferon 12 months prior to inclusion in the study.
  6. 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.
  7. Uncontrolled congestive heart failure (NYHA stade ≥ 2).
  8. Diffuse bone marrow infiltration on the baseline 68Ga-DOTATATE PET/CT confirmed by MRI.
  9. Prior external beam radiotherapy on kidneys or on more than 25% of bone marrow.
  10. Patients with known uncontrolled brain metastases.
  11. 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).
  12. Known autoimmune hepatitis.
  13. Patients after organ transplantation under immunosuppressive therapy.
  14. 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.
  15. Hypersensitivity to interferon α-2b or to any component of the product.
  16. Pregnant or lactating patients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01860742


Locations
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Belgium
Jules Bordet Institute
Brussels, Belgium, B-1000
UZ Leuven
Leuven, Belgium, B-3000
Sponsors and Collaborators
Jules Bordet Institute
Investigators
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Principal Investigator: Patrick Flamen, M.D., Ph.D. Jules Bordet Institute
Principal Investigator: Christophe Deroose, M.D., Ph.D. UZ Leuven

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Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT01860742     History of Changes
Other Study ID Numbers: IJBMNCASTOR
2012-005545-20 ( EudraCT Number )
First Posted: May 23, 2013    Key Record Dates
Last Update Posted: April 5, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Jules Bordet Institute:
Peptide Receptor Radionuclide Therapy (PRRT)
Neuroendocrine Tumors
Interferon alpha
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Interferons
Interferon-alpha
Interferon alpha-2
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs