Clinical trial NCT03422029: Efficacy and Safety of 177Lu-Dotatate PRRT in Metastatic GEP-NEN Patients
Official title: Study to Evaluate the Efficacy and Safety of 177Lu-Dotatate PRRT in Metastatic GEP-NEN Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: ORR
Safety
PFS
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 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
measure: Incidence of Treatment-related Adverse Events（Safety and Tolerability）
timeFrame: 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 outcomes:
measure: Progression-free survival
timeFrame: baseline, every 8 weeks up to 1 year after last patient first treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: