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177Lu-DOTATOC for the Treatment of Patients With Somatostatin Receptor Positive NETs

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ClinicalTrials.gov Identifier: NCT04915144
Recruitment Status : Not yet recruiting
First Posted : June 7, 2021
Last Update Posted : November 16, 2021
Sponsor:
Information provided by (Responsible Party):
British Columbia Cancer Agency

Tracking Information
First Submitted Date  ICMJE April 28, 2021
First Posted Date  ICMJE June 7, 2021
Last Update Posted Date November 16, 2021
Estimated Study Start Date  ICMJE January 1, 2022
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2021)
  • Determine whether personalized 177Lu-DOTATOC PRRT reduces adverse events (AE). [ Time Frame: 8 months ]
    Frequency of AEs, will be compared between the two treatment arms.
  • Compare the 12-month progression-free survival (PFS) of subjects receiving personalized or standard injected activity PRRT with RECIST criteria. [ Time Frame: 12 months ]
    PFS will be determined by RECIST1.1 criteria on serial CT, and analysed independently. The 12-month PFS will be evaluated by univariate analysis but different criteria for determination of PFS will be compared.
  • Compare the 12-month progression-free survival (PFS) of subjects receiving personalized or standard injected activity PRRT with ITMO criteria. [ Time Frame: 12 months ]
    PFS will be determined by biochemical criteria (ITMO) on serial CT, and analysed independently. The 12-month PFS will be evaluated by univariate analysis but different criteria for determination of PFS will be compared.
  • Compare the 12-month progression-free survival (PFS) of subjects receiving personalized or standard injected activity PRRT with Choi criteria. [ Time Frame: 12 months ]
    PFS will be determined by Choi criteria on serial CT, and analysed independently. The 12-month PFS will be evaluated by univariate analysis but different criteria for determination of PFS will be compared.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2021)
  • Determine response rate of both treatment arms with RECIST1.1 criteria [ Time Frame: 4 months ]
    Response rate as determined by structural criteria RECIST1.1
  • Determine response rate of both treatment arms with Choi criteria [ Time Frame: 4 months ]
    Response rate as determined by structural criteria Choi.
  • Determine response rate of both treatment arms with ITMO criteria [ Time Frame: 4 months ]
    Response rate as determined by structural criteria biochemical markers (ITMO criteria) (chromogranin A, 24h urinary HIAA).
  • Quality of life (QoL) questionnaire scores (EORTC QLQ30) will be compared between the two treatment arms [ Time Frame: 8 months ]
    For QoL questionnaire scores (EORTC QLQ30) before, during, and after treatment
  • Quality of life (QoL) questionnaire scores (EORTC GINET21) will be compared between the two treatment arms [ Time Frame: 8 months ]
    For QoL questionnaire scores (EORTC GINET21) before, during, and after treatment
  • Quality of life (QoL) questionnaire scores (EQ-5D) will be compared between the two treatment arms [ Time Frame: 8 months ]
    For QoL questionnaire scores (EQ-5D) before, during, and after treatment
  • Correlation of QoL scores (EORTC QLQ30) to ctDNA [ Time Frame: 8 months ]
    To assess correlation of QoL scores (EORTC QLQ30) to ctDNA allele frequency change from pre-treatment to on-treatment, using spearman correlation
  • Correlation of QoL scores (EORTC GINET21) to ctDNA [ Time Frame: 8 months ]
    To assess correlation of QoL scores (EORTC GINET21) to ctDNA allele frequency change from pre-treatment to on-treatment, using spearman correlation
  • Correlation of QoL scores (EQ-5D) to ctDNA [ Time Frame: 8 months ]
    To assess correlation of QoL scores (EQ-5D) to ctDNA allele frequency change from pre-treatment to on-treatment, using spearman correlation
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 31, 2021)
PFS and QoL scores to ctDNA levels [ Time Frame: 8 months ]
To assess correlation of PFS and QoL scores (EORTC QLQ30) to ctDNA levels (ctDNA allele frequency change from pre-treatment to on-treatment), the following tests will be used, Spearman correlation for quality of life and Kaplan- Meier curves stratified at a median for PFS.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE 177Lu-DOTATOC for the Treatment of Patients With Somatostatin Receptor Positive NETs
Official Title  ICMJE A Prospective Randomized Study of the Efficacy and Safety of 177Lu-DOTATOC With Either Standard or Personalized Dosing for the Treatment of Patients With Somatostatin Receptor Positive NETs
Brief Summary This study is to assess if personalized peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATOC results in fewer adverse events than standard PRRT. Subjects will be randomized to either receive personalized or standard PRRT. Personalized PRRT will be determined based on dosimetry calculations after the first cycle. In addition comparisons, will be made with progression-free survival, serial CT imaging, ctDNA, and quality of life questionnaires. Subjects will be followed for 5 years or until they have progression and are switched to another systemic treatment (not including treatment with somatostatin analogues).
Detailed Description

Overall, 200 subjects will be randomized (1:1 randomization ratio) to receive standard injected activities of 177Lu-DOTATOC PRRT or personalized injection of 177Lu-DOTATOC PRRT. Randomization will be stratified for grade and primary location.

Screening Phase: Subjects will be screened against the inclusion and exclusion criteria. Screening by SSR imaging will be completed to determine expression of SSR and feasibility of treatment by PRRT. Once eligibility has been confirmed they will be randomized. Subjects will undergo a physical exam, complete a medical history questionnaire, quality of life questionnaires, blood work, and a diagnostic CT.

Treatment Phase: During the treatment phase, subjects will undergo 4 cycles of treatment. Each treatment cycle will be followed by 2 dosimetry SPECT/CT scans on day 1 (18 - 32 hours after treatment administration) and day 2 (64 - 80h after treatment administration) After cycle 3 quality of life questionnaires will be completed again.

Follow up Phase: At the end of treatment or after discontinuation of any cause, subjects will be followed for 5 years to continue data collection for the other objectives. Objective tumour response will be assessed every 6 months by diagnostic CT according to the RECIST 1.1 criteria.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a prospective randomized phase II study two-arm study of efficacy and safety of 177Lu-DOTATOC for treatment of patients with NETs who are referred to BC Cancer - Vancouver for treatment of progressive tumours.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Carcinoid Tumor
  • Pulmonary Carcinoid Tumor
  • Gastroenteropancreatic Neuroendocrine Tumor
  • Vipoma
  • Insulinoma
  • Gastrinoma
Intervention  ICMJE Drug: 177Lu-DOTATOC
Subjects will receive 177Lu-DOTATOC PRRT treatment over 4 cycles, each cycle occurs every 8 weeks.
Study Arms  ICMJE
  • Active Comparator: Standard PRRT
    For standard PRRT 177Lu-DOTATOC therapy, the administered activity will be 7.4 GBq ± 10% as an intravenous infusion over a time of 10 to 30 minutes.
    Intervention: Drug: 177Lu-DOTATOC
  • Experimental: Personalized PRRT
    For 177Lu-DOTATOC therapy, for the first cycle the administered activity will be 7.4 GBq ± 10% as an intravenous infusion over a time of 10 to 30 minutes.Subsequent cycles will be adjusted based on dosimetry calculations.
    Intervention: Drug: 177Lu-DOTATOC
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 31, 2021)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2027
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Able to provide written informed consent
  • Age greater than or equal to 19 years
  • Biopsy-proven, well-differentiated grade 1 - 3 NET
  • Gastroenteropancreatic tumors (e.g. carcinoids, gastrinoma, insulinoma, glucagonoma, VIPoma, etc.), functioning and non-functioning
  • Sympathoadrenal system tumors (phaeochromocytoma, paraganglioma)
  • Pulmonary NET, functioning and non-functioning
  • Easter Cooperative Oncology Group (ECOG) ≤ 2
  • Ki67 ≤ 55%
  • Progressive disease demonstrated by RECIST 1.1 criteria within the 6 months preceding the study.
  • Patients with other evidence of progressive disease that is not demonstrated on CT (like rising biomarkers) may be included, at the discretion of the Tumour Review Board.
  • If response to other treatments is considered adequate according to other criteria, the Tumour Review Board may consider excluding the patient from participation in the study.
  • Tumour Review Board confirmation of suitability to proceed to PRRT treatment and enrollment in this trial.
  • Positive PET SSR imaging (Krenning score 2 or higher) in previous 6 months (68Ga-DOTATOC, 68Ga-DOTATATE, 18F-AmBF3-TATE). If PET SSR imaging is not available 111In-penetreotide scintigraphy (Octreotide scan) is acceptable.
  • Adequate laboratory parameters within two weeks of enrollment
  • Kidneys

    • Serum creatinine ≤ 150 µmol/L
    • GFR ≥ 40 ml/min (using plasma clearance values)
  • Marrow

    • Hemoglobin ≥ 80 g/L
    • WBC ≥ 2 x 109/L
    • Platelets ≥ 75 x 109/L
    • Liver
  • Total bilirubin ≤ 3 x upper limit of normal (ULN)
  • ALT ≤ 3 x ULN or ≤ 5 x ULN if liver metastasis
  • Alkaline phosphatase ≤ 3 x ULN or ≤ 5 x ULN if liver metastasis
  • Subject's ability to comply with scheduled visits, treatment plans, laboratory tests, imaging tests, and other procedures required as detailed in the protocol.

Exclusion Criteria:

  • Women and men of childbearing potential Procreation

    • Women: pregnancy test done before enrollment before each treatment cycle. And subject must use adequate contraception for the duration of therapy, be surgically sterile, or post-menopausal.
    • Men: must be surgically sterile or use adequate contraception for the duration of the therapy.
  • Patient with another non-cutaneous (excluding melanoma) active cancer requiring therapeutic intervention.
  • Curative medical or surgical treatment, local liver embolization, or debulking are appropriate options.
  • Life expectancy is less than 12 weeks.
  • Radiotherapy to target lesions ≤ 12 weeks ago or to more than 25% of bone marrow.
  • PRRT at any time prior to randomization in this study.
  • Systemic therapy (chemotherapy) within 4 weeks of PRRT and other locoregional therapies (radioisotope, embolization) within 12 weeks prior to enrollment. Ongoing use of somatostatin analogs for control of symptoms is allowed.
  • Known brain metastases (unless treated and stable for more than 3 months).
  • Co-morbidities that could, in the opinion of the PI, interfere with safe delivery of PRRT (like urinary incontinence, psychiatric illness), uncontrolled congestive heart failure (NYHA II, III, IV)
  • Breastfeeding (if patients elect to discontinue breast feeding, they can participate in the trial).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Administrative Research Manager 604-877-6000 ext 2818 hayley.allan@bccancer.bc.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04915144
Other Study ID Numbers  ICMJE H20-03401
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party British Columbia Cancer Agency
Study Sponsor  ICMJE British Columbia Cancer Agency
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Francois Benard, MD BC Cancer
PRS Account British Columbia Cancer Agency
Verification Date November 2021

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