177Lutetium-DOTA-Octreotate Therapy in Somatostatin Receptor-Expressing Neuroendocrine Neoplasms

This is a phase II treatment protocol evaluating 177Lu-DOTATATE therapy for somatostatin receptor-expressing cancers including, but not limited to, those arising from the neural crest and involving such organs as the lungs, breast, gastrointestinal tract, skin, and endocrine (examples: pheochromocytoma, medullary carcinoma of the thyroid, non-radioiodine avid differentiated thyroid cancer, melanoma, renal cell, Merkel cell, paraganglioma, small cell lung, Carcinoid, and pancreatic islet cell malignancies).

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: 177Lu-DOTATATE

Detailed Description

(177)Lutetium-DOTA-Octreotate Therapy in Somatostatin Receptor-Expressing Neuroendocrine Neoplasms

First Annual Report on protocol IND# 78,256 at RITA Foundation in collaboration with Excel diagnostics and Nuclear Oncology center and Baylor College of Medicine

Protocol number 78,256 calls for recruitment of sixty patients on this protocol. As of August 15th, 2011, we have enrolled 23 patients on this study ages between 27 and 83 years old with average of 61.6. Among patients there were 22 Caucasians (95.7%) and 1 African American (4.3 %). Eleven of the patients were female (48%) age between 46 and 83 years old with average of 63.9 years old. Twelve male patients (52%) were treated with ages between 27 and 86 years old with average of 59.58 years old. 15 patients (65.2%) had Gastro-entero-pancreatic neuroendocrine tumor (GEPNET), 7 had carcinoid tumors (30.4%) and 1 had bronchial carcinoid (4.3%). All patients had progressive disease with multiple distant metastases that poorly responded to prior surgery, chemotherapy, radiotherapy, chemo-embolization or cold Octreotide treatments.

Full phase I dosimetry evaluation, including dosimetric evaluation of multiple urine and blood sample collections, was performed on 6 patients and submitted to FDA. Ten patients received one therapy with an average dose of 199mCi/patient (188.52-208.15 mCi). Eight patients received two cycles of therapies with an average dose 390.29mCi/patient (363.49-413.26 mCi). Two patients received three therapies with an average dose 592.11mCi/patient (587.52-596.7mCi) and three patients have received four therapies with an average dose of 787.62mCi/patient (784.21-794.28 mCi).

Toxicity

Patients were evaluated for any evidence of renal, hepatic or hematologic toxicity using NCI common toxicities criteria following each cycle of therapy. No significant acute toxicity was observed immediately following treatment, and no patients required supportive treatment during therapy. Of 23 evaluable patients, 6 patients (26%) had grade 2 or 3 hematological toxicity which no supportive therapy was required. Average duration of hematological toxicities grade 2 was 8.3 weeks (range 4-16 weeks) and 4.5 weeks (range 1-8 weeks) for toxicity grade 3. Grade 2 or 3 liver toxicity was observed in 2 patients (8.6%). In addition, 2 patients (8.6%) had renal toxicity grade 2. 11 patients (47.8%) had moderate or severe nausea/vomiting after their treatment recovered between 1 to 3 days after completion of therapy. In one patient (4.3%), skin flushing, sweating and diarrhea developed after the therapy which recovered within 48 hours following the therapy.

Response

Among 13 patients who have received 2 or more cycles of therapy, 4 (30%) had a partial response to treatment and 9 patients (70%) exhibited stable disease. No disease progression was noted.

4 patient deaths have been reported so far. None of these patients were able to complete all four cycles of the therapy. All patients died as a result of massive tumor burden. The average time interval between the death and the last treatment is 1.41 months (0.76-2.23 months).

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77042
      • Excel Diagnostics and Nuclear Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with biopsy proven Gastroenteropancreatic (GEP tumors including bronchial carcinoids)
• Presence of somatostatin-receptors on the known tumor lesions demonstrated by OctreoScan within 6 months of the first dose of radiolabelled octreotate therapy. The uptake on the OctreoScan should be at least as high as normal liver uptake on planar imaging.
• Life Expectancy greater than 12 weeks.
• Serum creatinine ≤ 150 µmol/liter or 1.7 mg/dL and a measured creatinine clearance (or measured GFR using plasma clearance methods, not gamma camera based) of ≥ 50ML/min.
• Hemoglobin (Hgb) concentration ≥ 5.5 mmol/L (≥ 8.9 g/dL); WBC ≥ 2*109/L (2000/mm3); platelets ≥ 100*109/L (100*103/mm3).
• Total Bilirubin ≤ 3X UNL.
• Serum Albumin > 30g/L or serum albumin ≤ 30g/L but normal prothrombin time.
• All patients must have a Karnofsky performance status of at least 60%
• Patients must be greater than 18 years of age. Patients younger than 18 years will be presented to FDA for compassionate use on a case by case basis

Exclusion Criteria:

• Possible surgery with curative intent.
• Surgery, radiotherapy, chemotherapy or other investigational therapy within 3 months of the start of therapy.
• Patients with known brain metastases unless these metastases have been treated and stabilized for at least 6 months prior to study start. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to study start.
• Uncontrolled congestive heart failure.
• Any subject who is taking concomitant medications which decrease renal function (such as aminoglycoside antibiotics).
• Any subject receiving therapy with somatostatin analogues, unless the dose has been stable for at least 3 months prior to the first cycle in this study and the disease status during these 4 months has been documented by modified RECISTS criteria as described in this study
• Any subject receiving therapy with short acting somatostatin analogues in whom these analogues cannot be interrupted for 12 hours before and 12 hours after the administration of the radio labelled somatostatin analogues, or any subject who receives therapy with long-acting somatostatin analogues in whom these analogues cannot be interrupted for at least 6 weeks before the administration of the radio labeled somatostatin analogues, unless the uptake on the Octreoscan during continued somatostatin analogue medication is at least as high as normal liver uptake on planar imaging.
• In patients with unusual hematological parameters, including an increased MCV (>105fL), and especially in those who had previous chemotherapy, the advice of a hematologist should be sought for adequate further work-up.
• Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
• Prior radiation therapy to more than 25% of the bone marrow.
• Female patients who are pregnant, lactating or women of childbearing potential not willing to practice effective contraceptive techniques during the study period and for 60 days (10 half lives of 177Lu after the last treatment, or male patients who have female partners of childbearing potential not willing to practice abstinence or effective contraception, during the study period and for 60 days after the last treatment

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: Treatment; Patients with somatostatin receptor-expressing neuroendocrine neoplasms will receive up to 200 mCi of 177Lu-DOTATATE every 6-11 weeks, preferably 6-9 weeks to a cumulative dose of 800 mCi.	Drug: 177Lu-DOTATATE; Patients will receive 200mCi dose of 177Lu Dotatate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free survival	Overall response will be determined by Progression Free Survival (PFS). PFS will be calculated as a function of time from start of therapy to time of overall disease progression. Patients will be censored at the date of last contact	one year after completion of last treatment cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity	Patients will be monitored for dose toxicity according to NCI guidelines	one year after completion of the fourth cycle of treatment

Collaborators and Investigators

• Sponsor: Ebrahim S Delpassand
• Collaborators: Excel Diagnostics and Nuclear Oncology Center
• Investigators: Principal Investigator: Ebrahim S Delpassand, M.D, Excel Diagnostics and Nuclear Oncology Center

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2010
• Primary Completion (Actual): November 17, 2016
• Study Completion (Actual): July 25, 2017

Study Registration Dates

• First Submitted: November 8, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (Estimate): November 9, 2010

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Lutetium Lu 177 dotatate
• Other Study ID Numbers: 78,256

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