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

Brief Title

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

Official Title

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Determine whether personalized 177Lu-DOTATOC PRRT reduces adverse events (AE).

Secondary Outcome

 Determine response rate of both treatment arms with RECIST1.1 criteria

Condition

Neuroendocrine Tumors

Intervention

177Lu-DOTATOC

Study Arms / Comparison Groups

 Standard PRRT
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

200

Start Date

October 1, 2021

Completion Date

December 31, 2027

Primary Completion Date

December 31, 2023

Eligibility Criteria

        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).
      

Gender

All

Ages

19 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Francois Benard, MD, 604-877-6000, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT04915144

Organization ID

H20-03401


Responsible Party

Sponsor

Study Sponsor

British Columbia Cancer Agency


Study Sponsor

Francois Benard, MD, Principal Investigator, BC Cancer


Verification Date

August 2021