Efficacy and Safety of 177Lu-Dotatate PRRT in Metastatic GEP-NEN Patients

Study to Evaluate the Efficacy and Safety of 177Lu-Dotatate PRRT in Metastatic GEP-NEN Patients

The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Dotatate in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of GEP-NEN

Study Overview

• Status: Unknown
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: 177Lu-Dotatate PRRT

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. sign written informed consent form
2. age ≥ 18 years
3. pathologically confirmed well-differentiated neuroendocrine tumors;
4. unresectable metastatic tumors confirmed by radiological imaging;
5. Somatostatin receptor positive (SSTR+) disease;
6. Radiological disease progression within 12 months, defined as progressive disease per RECIST 1.1. criteria
7. No more than 2 prior antitumor drugs, including somatostatin analogs, targeted drugs and chemotherapy, with the last dose over 4 weeks;
8. At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan >=20mm, spiral CT scan >=10mm, no prior radiation to measurable lesions);
9. Screening laboratory values must meet the following criteria (within past 7 days): hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ μL; platelets ≥ 100 x 10^3/ μL; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1╳ULN;
10. KPS ≥ 70;
11. Predicted survival >=3 months;
12. Negative serum or urine pregnant test within 7 days prior to randomization for child-bearing age women;
13. Sexually active males or females willing to practice contraception during the study until 30 days after end of study.

Exclusion Criteria:

1. Hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative;
2. Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
3. Received surgery within past 4 weeks, or have not recovered from surgery;
4. Concurrent severe infection；
5. Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including severe liver disease (active hepatitis, cirrhosis), uncontrolled diabetes or hypertension, or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm);
6. Prior long term steroid therapy (excluding short term steroid treatment which is completed prior to > 2 weeks of study enrollment)；
7. Meningeal carcinomatosis;
8. Patients with central nervous system(CNS) disorder or peripheral nervous system disorder or psychiatric disease；
9. Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, or congestive heart failure, or cardiac infarction within 6 months prior to study enrollment, or cardiac insufficiency；
10. Pregnant or nursing, or sexually active males or females refuse to practice contraception during the study until 30 days after end of study;
11. History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible；
12. Person with no capacity (legally) or inappropriate to continue study treatment for ethics/medical reasons；
13. Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 177Lu-Dotatate PRRT; 177Lu-Dotatate A maximum of 8 cycles of 1000mCi 177Lu-Dotatate, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 8 cycles, every 8 weeks	Drug: 177Lu-Dotatate PRRT; PRRT using 177Lu-Dotatate 100-150mCi will be performed 8-weekly. A maximum of 8 cycles will be administered. Other: Amino-Acid Solution The Amino-Acid Solution (AAS) to be used in this study, infused over 4-6 h, starting 30 min before PRRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	CT/MRI will be performed every 8 weeks for efficacy evaluation by RECIST 1.1 and CHOI	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Incidence of Treatment-related Adverse Events（Safety and Tolerability）	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause	baseline, every 8 weeks up to 1 year after last patient first treatment

Collaborators and Investigators

• Sponsor: Peking University

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Safety; ORR; PFS
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Lutetium Lu 177 dotatate
• Other Study ID Numbers: PRRT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No