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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Excel Diagnostics and Nuclear Oncology Center
Sponsor:
Information provided by (Responsible Party):
Ebrahim S. Delpassand, Excel Diagnostics and Nuclear Oncology Center
ClinicalTrials.gov Identifier:
NCT01237457
First received: November 8, 2010
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

This is a phase II treatment protocol offering 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).


Condition Intervention Phase
Neuroendocrine Tumors
Drug: 177Lu-DOTATATE
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 177Lutetium-DOTA-Octreotate Therapy in Somatostatin Receptor-Expressing Neuroendocrine Neoplasms

Resource links provided by NLM:


Further study details as provided by Excel Diagnostics and Nuclear Oncology Center:

Primary Outcome Measures:
  • Progression Free survival [ Time Frame: one year after completion of last treatment cycle ] [ Designated as safety issue: Yes ]
    Overall response will be determinine 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 sensored at the date of last contact


Secondary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: one year after completion of the fourth cycle of treatment ] [ Designated as safety issue: Yes ]
    Patients will be monitored for dose toxicity according to NCI guidelines


Estimated Enrollment: 60
Study Start Date: October 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Drug: 177Lu-DOTATATE
Patients will receive 200mCi dose of 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 3 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 radiolabelled 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 radiolabeled 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01237457

Locations
United States, Texas
Excel Diagnostics and Nuclear Oncology Center Recruiting
Houston, Texas, United States, 77042
Contact: Susan Cork    713-341-3203    scork@exceldiagnostics.com   
Contact: Izabela Tworowska, PhD    713-590-0601    itworowska@radiomedix.com   
Sponsors and Collaborators
Excel Diagnostics and Nuclear Oncology Center
Investigators
Principal Investigator: Ebrahim S Delpassand, M.D Excel Diagnostics and Nuclear Oncology Center
  More Information

No publications provided

Responsible Party: Ebrahim S. Delpassand, Chairman and Medical Director, Excel Diagnostics and Nuclear Oncology Center
ClinicalTrials.gov Identifier: NCT01237457     History of Changes
Other Study ID Numbers: 78,256
Study First Received: November 8, 2010
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Somatostatin
Octreotide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 20, 2014