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

NCT04915144 | Withdrawn Phase 2

• 1 other identifier: H20-03401
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (9)

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

  4 months

• Determine response rate of both treatment arms with Choi criteria

  4 months

• Determine response rate of both treatment arms with ITMO criteria

  4 months

• Quality of life (QoL) questionnaire scores (EORTC QLQ30) will be compared between the two treatment arms

  8 months

• Quality of life (QoL) questionnaire scores (EORTC GINET21) will be compared between the two treatment arms

  8 months

Other Outcomes (1)

• PFS and QoL scores to ctDNA levels

  8 months

Study Arms (2)

Standard PRRT

ACTIVE COMPARATOR

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

Personalized PRRT

EXPERIMENTAL

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

Interventions

177Lu-DOTATOC DRUG

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

Personalized PRRT; Standard PRRT

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (1)

BC Cancer

Vancouver, British Columbia, V5Z 4E6, Canada

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoid Tumor; Gastro-enteropancreatic neuroendocrine tumor; Vipoma; Insulinoma; Gastrinoma

Interventions

177Lu-octreotide, DOTA(0)-Tyr(3)-

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Neuroendocrine; Carcinoma, Islet Cell; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma

Study Officials

• Francois Benard, MD

  BC Cancer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: June 7, 2021
• Study Start: January 15, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2031
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)