177Lu-DOTATOC For The Treatment Of Patients With Somatostatin Receptor Positive NETs

Study Overview

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

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).

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.

Neuroendocrine Tumors
Carcinoid Tumor
Pulmonary Carcinoid Tumor
Gastroenteropancreatic Neuroendocrine Tumor
Vipoma
Insulinoma
Gastrinoma

DRUG: 177Lu-DOTATOC

H20-03401

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-04-28	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-02-17
First Submitted that Met QC Criteria 2021-05-31	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-02-21
First Posted (ACTUAL) 2021-06-07	Results First Posted N/A	Last Verified 2023-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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.	DRUG: 177Lu-DOTATOC Subjects will receive 177Lu-DOTATOC PRRT treatment over 4 cycles, each cycle occurs every 8 weeks.
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.	DRUG: 177Lu-DOTATOC Subjects will receive 177Lu-DOTATOC PRRT treatment over 4 cycles, each cycle occurs every 8 weeks.

Participant Group/Arm

Intervention/Treatment

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.

DRUG: 177Lu-DOTATOC

Subjects will receive 177Lu-DOTATOC PRRT treatment over 4 cycles, each cycle occurs every 8 weeks.

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.

DRUG: 177Lu-DOTATOC

Subjects will receive 177Lu-DOTATOC PRRT treatment over 4 cycles, each cycle occurs every 8 weeks.

Primary Outcome Measures	Measure Description	Time Frame
Determine whether personalized 177Lu-DOTATOC PRRT reduces adverse events (AE).	Frequency of AEs, will be compared between the two treatment arms.	8 months
Compare the 12-month progression-free survival (PFS) of subjects receiving personalized or standard injected activity PRRT with RECIST criteria.	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.	12 months
Compare the 12-month progression-free survival (PFS) of subjects receiving personalized or standard injected activity PRRT with ITMO criteria.	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.	12 months
Compare the 12-month progression-free survival (PFS) of subjects receiving personalized or standard injected activity PRRT with Choi criteria.	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.	12 months

Secondary Outcome Measures	Measure Description	Time Frame
Determine response rate of both treatment arms with RECIST1.1 criteria	Response rate as determined by structural criteria RECIST1.1	4 months
Determine response rate of both treatment arms with Choi criteria	Response rate as determined by structural criteria Choi.	4 months
Determine response rate of both treatment arms with ITMO criteria	Response rate as determined by structural criteria biochemical markers (ITMO criteria) (chromogranin A, 24h urinary HIAA).	4 months
Quality of life (QoL) questionnaire scores (EORTC QLQ30) will be compared between the two treatment arms	For QoL questionnaire scores (EORTC QLQ30) before, during, and after treatment	8 months
Quality of life (QoL) questionnaire scores (EORTC GINET21) will be compared between the two treatment arms	For QoL questionnaire scores (EORTC GINET21) before, during, and after treatment	8 months
Quality of life (QoL) questionnaire scores (EQ-5D) will be compared between the two treatment arms	For QoL questionnaire scores (EQ-5D) before, during, and after treatment	8 months
Correlation of QoL scores (EORTC QLQ30) to ctDNA	To assess correlation of QoL scores (EORTC QLQ30) to ctDNA allele frequency change from pre-treatment to on-treatment, using spearman correlation	8 months
Correlation of QoL scores (EORTC GINET21) to ctDNA	To assess correlation of QoL scores (EORTC GINET21) to ctDNA allele frequency change from pre-treatment to on-treatment, using spearman correlation	8 months
Correlation of QoL scores (EQ-5D) to ctDNA	To assess correlation of QoL scores (EQ-5D) to ctDNA allele frequency change from pre-treatment to on-treatment, using spearman correlation	8 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
19 Years

Accepts Healthy Volunteers:

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.

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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Francois Benard, MD, BC Cancer

Publications

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