A Multicenter Study Evaluating Efficacy and Safety of 177Lu-DOTA-TATE Based on Kidney-Dosimetry in Patients With Disseminated Neuroendocrine Tumors

NCT ID: NCT01456078

Last Updated: 2019-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2018-11-30

Brief Summary

By improved kidney dosimetry including biological effective dose and taking into account potential risk factors (especially for kidney toxicity), it might be possible to give an optimal and personalized treatment with 177Lu-DOTA-TATE to the patient with metastatic neuroendocrine tumor.

Conditions

Neuroendocrine Tumors; Liver Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

177Lu-DOTA-TATE

Group Type: EXPERIMENTAL

177Lu-DOTA-TATE

Intervention Type: DRUG

177Lu-DOTA-TATE given as intravenous infusion given during 3-5 treatments. Evaluation is performed after every single cycle. Further more, evaluation is made after last cycle, and delivered cumulative dose to kidneys should be 27 Gy.

Patients with stable disease or partial response, and without pronounced toxicity will continue treatment to a step 2, where additional 3-5 treatment cycles are given, with a cumulative dose to kidneys to 40 Gy.

Interventions

177Lu-DOTA-TATE

177Lu-DOTA-TATE given as intravenous infusion given during 3-5 treatments. Evaluation is performed after every single cycle. Further more, evaluation is made after last cycle, and delivered cumulative dose to kidneys should be 27 Gy.

Patients with stable disease or partial response, and without pronounced toxicity will continue treatment to a step 2, where additional 3-5 treatment cycles are given, with a cumulative dose to kidneys to 40 Gy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Step 1:

• ECOG 0-2
• Histologically verified neuroendocrine tumors with a Ki67 of at least 20 % or at least 20 mitoses/high power fields. If the tissue on which this determination is based is several years old, the investigator should consider the option of acquiring a new determination, especially if the behaviour of the tumor has changed since diagnosis
• Metastatic disease where complete resection is not considered possible or feasible
• Measurable disease
• Radiological disease progression during the last 14 months
• The largest metastases should have an uptake of 111In-octreotide that is greater than the uptake in the liver by planar scintigraphy. Metastases that are small, or located centrally, can be evaluated by SPECT to enable a correct estimation of the relative uptake. The majority of the tumor burden must demonstrate an increased uptake for lutetium-treatment to be considered
• Stable dose of somatostatin analogue for the past 3 months
• Estimated survival more than 6 months
• ANC more than 1.5 x 10 9/L
• Bilirubin less than 1.5 x upper limit of normal
• GFR more than 50 ml/min.
• Signed written informed concent

Step 2:

• A maintained GFR (less than 40 % decrease compared to baseline AND GFR more than 50 ml/min)
• The treatment in step 1 have been administered with a maximal interval of 12 weeks
• Age under 70 years

Exclusion Criteria

Step 1:

• Performance Status ECOG 3-4
• Proliferation index (Ki67) more than 20 % or more than 20 mitoses/hpf
• Loco-regional treatment during the last 3 months involving all of the measurable lesions
• Chemotherapy during the last 3 months, or longer if persisting toxicity exists. Earlier treatment with mTORi or TKI is permitted
• Other concommitant nephrotoxic treatment
• Modifications of the somatostatine dose in the last 3 months
• Serious heart disease
• Previous radiotherapy including more than 25 % of active bone marrow volume
• Pregnancy and lactation
• Extensive liver metastases (more than 50 % of liver volume)
• Symptomatic CNS metastases requiring corticosteroid treatment
• Ongoing treatment with interferon. This treatment should be suspended a minimum of 4 weeks before treatment with 177Lu-DOTA-TATE, or longer if there is persisting signs of toxicity
• Patients who have another metastatic tumor diagnosis

Step 2:

• Progressive disease since start of study treatment
• Organ toxicity grade 3-4 during step 1
• Serious hematological toxicity during previous treatment cycles (ANC less than 0.5 x 10 9 or platelets less than 50.0 x 10 9)
• Longstanding diabetes (more than 8 years). Patients with a well-controlled diabetes with a history of less than 8 years and a blood pressure less than 130/80 and no albuminuria (albumin/creatinine index)can be included
• Hypertension, i.e. more than 160/90 (for diabetics more than 130/80). Antihypertensive pharmacological treatment is permitted as long as there is no manifest albuminuria
• Previous liver embolisation
• Previous chemotherapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lund University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Tennvall, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology, Lund University Hospital

Locations

Sahlgrenska University Hospital, Department of Oncology

Gothenburg, , Sweden

Department of Oncology, Lund University Hospital

Lund, , Sweden

Countries

Sweden

References

Sundlov A, Gleisner KS, Tennvall J, Ljungberg M, Warfvinge CF, Holgersson K, Hallqvist A, Bernhardt P, Svensson J. Phase II trial demonstrates the efficacy and safety of individualized, dosimetry-based 177Lu-DOTATATE treatment of NET patients. Eur J Nucl Med Mol Imaging. 2022 Sep;49(11):3830-3840. doi: 10.1007/s00259-022-05786-w. Epub 2022 Apr 22.

Reference Type: DERIVED

PMID: 35451612 (View on PubMed)

Other Identifiers

EudraCT number: 2011-000240-16

Identifier Type: -

Identifier Source: org_study_id