Efficacy of 177-Lu-DOTA 0, Tyr 3 Octreotate

Efficacy of Peptide Receptor Radionuclide Therapy for Metastatic Inoperable Neuroendocrine Tumors Using 177-Lu-DOTA 0, Tyr 3 Octreotate

Well-differentiated neuroendocrine tumors (WDNETs) are uncommon neoplasms with an increasing number of new cases reported in the annual statistics of the Instituto Nacional de Cancerología (INC). The majority are advanced-stage presentations with limited chances of a complete surgical resection of the primary tumor, a clinical scenario where medical treatment options are also limited. In view of the characteristically defined expression of peptide receptors in WDNETs, radioactive molecular probes to target specific cellular receptors have been designed using radioisotopes with short range of penetration in tissues. We have designed a one-arm phase II prospective sequential clinical trial to assess the therapeutic efficacy of 177-Lu-[DOTA 0, Tyr 3] octreotate (177-Lu- DOTATATE) applied intravenously in three separate doses to patients with inoperable progressive WDNET. Selected patients matching inclusion criteria will be enrolled at the INC's Section of Endocrinology. Tumor response, treatment safety (side effects) and survival will be appraised. Data from clinical, biochemical and imaging follow-up will be periodically registered during treatment and until two years after the last infusion of 177Lu- DOTATATE. This phase II trial is justified because despite the fact that many preclinical and clinical studies have showed the potential usefulness of this novel palliative approach to treat patients with advanced-stage WDNETs there is a paucity of vigorous results to establish its efficacy as first-line treatment.

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Radiation: [177Lu] DOTA-TATE

Detailed Description

The Investigators have designed a one-arm phase II prospective sequential clinical trial to assess the therapeutic efficacy of 177-Lu-[DOTA 0, Tyr 3] octreotate (177-Lu- DOTATATE) applied intravenously in three separate doses to patients with inoperable progressive WDNET.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 00000
      • Instituto Nacional de Cancerologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with inoperable gastroenteropancreatic neuroendocrine tumors.
• Histopathologic diagnosis confirmed at the Instituto Nacional de Cancerología.
• Somatostatin receptor-positive tumors with at least one site of abnormal focal uptake > liver physiologic uptake (3+) observed in a 99mTc-HYNIC-TOC scintigraphy practiced less than 6 months before treatment with 177Lu- DOTATATE.
• Karnofsky functional score > 60.
• Life expectancy > 3 months.
• Multiple inoperable metastatic sites.
• Patient voluntarily willing to participate in the trial.
• Hemoglobin (Hb) > 8.8 g/dl
• Leucocytes (Leu) > 2 x 103/µl
• Platelets (Plaq) > 80 x 103/µl
• Total Bilirrubin (BT) ≤ 3 times the upper limit of normal range. Serum albumin > 3 g/dl and normal prothrombin time.
• At least one measurable CT tumor lesion.
• Non-lactating woman with negative pregnancy blood test.
• Creatinine clearance > 40 ml/min and serum creatinine < 1.5 mg/dl and/or isotopic glomerular filtration rate > 50 ml/min.
• Test results should predate treatment by at least: blood test results ≤ 4 weeks, liver blood tests < 1 month, renal function tests < 1 week, CT ≤ 4 months and 99mTc-HYNIC-TOC scintigraphy < 6 months.

Exclusion Criteria:

• Patients previously treated with radionuclide therapy.
• Patients treated with chemo- o radiotherapy within the past 6 months.
• Patients unable to comply with clinical follow-up in both Nuclear Medicine and Endocrinology units.
• Patients unwilling to participate in the trial or not providing written informed consent.

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] DOTA-TATE; We have designed a one-arm phase II prospective sequential clinical trial to assess the therapeutic efficacy of 177-Lu-[DOTA 0, Tyr 3] octreotate (177-Lu- DOTATATE) applied intravenously in three separate doses to patients with inoperable progressive WDNET.	Radiation: [177Lu] DOTA-TATE; We have designed a one-arm phase II prospective sequential clinical trial to assess the therapeutic efficacy of 177-Lu-[DOTA 0, Tyr 3] octreotate (177-Lu- DOTATATE) applied intravenously in three separate doses to patients with inoperable progressive WDNET.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment	Response to palliative treatment with 177Lu- DOTATATE in patients with metastatic progressive low-grade neuroendocrine tumors defined by control size tumor, response time to reduction minimal parcial and complete tumor.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy defined by reduction in size tumoral	Measure the efficacy of 177Lu- DOTATATE to treat patients with metastatic progressive low-grade neuroendocrine tumors using clinical and imaging criteria such as tumor size.	3 years
Side effects defined by clinical follow up	Describe the side effects of the treatment with 177Lu- DOTATATE by clinical follow-up during and after therapy	5 years
survival rate	describe the 2-year survival rate of patients treated with 177Lu- DOTATATE	2 years
Quality of life	Assess the quality of life of patients with metastatic progressive low-grade neuroendocrine tumors treated with 177Lu- DOTATATE during treatment defined by pain reduction and tolerability.	3 years

Collaborators and Investigators

• Sponsor: Instituto Nacional de Cancerologia, Columbia
• Investigators: Principal Investigator: Carmen A De los Reyes, Md, Instituto Nacional de Cancerologia

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: April 25, 2014
• First Posted (Estimate): April 29, 2014

Study Record Updates

• Last Update Posted (Actual): November 14, 2019
• Last Update Submitted That Met QC Criteria: November 12, 2019
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Treatment Outcome; Neuroendocrine Tumors; Lutetium
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors
• Other Study ID Numbers: C41030610-041