Excel Diagnostics

Novel Radio-peptide Targeted Therapy Clinical Trial approved by FDA for Neuroendocrine Cancers

Excel Diagnostics & Nuclear Oncology Center is pleased to announce that after careful review the Federal Drug Administration (FDA) has approved Investigational New Drug Clinical Trial by LU-177 Octreotate for patients with Neuroendocrine cancers. Excel Diagnostics & Nuclear Oncology Center is the first research facility in North America to receive authorization to initiate this much needed cancer therapy.

This therapy can be applied to the category of neuroendocrine tumors which include Carcinoid, Islet Cell Carcinoma of the Pancreas, Oat Cell Carcinoma of the Lung, Pheochromocytoma, and Iodine refractory or Medullary Thyroid Carcinoma”.

The principle investigator of this program is Dr. Ebrahim S. Delpassand and the project is in collaboration with St. Luke’s Episcopal Hospital and Radio-Isotope Therapy of America (RITA) Foundation in Houston.

For further information regarding this treatment please contact Ms. Susan Cork at scork@exceldiagnostics.com or call 713-341-3203.

We at Excel Diagnostics & Nuclear Oncology Center are proud to be part of yet another exciting therapy in the fight against Neuroendocrine cancers.

Introduction and Background Information

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that arise from Kulchinsky cells that populate the thymus, bronchus and gut. Regardless of their primary site, NETs share similar histological, metabolic and ultrastructural features 1. Many NETs are found during surgery for other diagnoses, such as appendicitis, pancreatitis or small bowel obstruction. The average time from symptom onset to diagnosis is sometimes more than 9 years 2. The indolent nature of NETs lead most patients seek treatment for their tumor when it has already metastasized limiting their overall survival 3. Therapeutic options for patients with advanced disease are often limited. Single agent or combination chemotherapy regimens for management of “typical” slow growing NETs have not been efficacious. Furthermore, external-beam radiation therapy has not demonstrated significant efficacy in establishing local control in NETs. Interferon (IFN) therapy has also been used in protocol-based management of Carcinoid tumors with reported biochemical and tumor response rates of 40% and 12% respectively 4, 5. However, IFN therapy is associated with numerous toxicities including fever, anorexia, weight loss, fatigue and myelosuppression. Due to the high incidence of toxicity and the low tumor response rate, the routine use of IFN for NETs is rarely recommended in the USA.

Peptide Receptor Radionuclide Therapy (PRRT)

PRRT is a therapeutic approach that uses the affinity of special peptide (small protein) called Octreotide for targeting the NET tumor cells. When this peptide is attached to radioactive materials such as Indium-111, Lu-177 or Y-90, it can deliver significant amount of radiation specifically to tumor cells (Targeted Therapy). While medication is administered systemically, the radioactive peptide only resides at the site of the tumor cells, wherever they exist in the body, and washes out rapidly from the normal organs. Therefore, the therapeutic effect of radioactive material will occur in the region of the tumors with minimal and reversible effects on the normal tissue. This is the reason for typically mild side effects secondary to this treatment approach when is compared with systemic chemotherapy.

High Activity Indium-111 Octreotide Therapy

Indium-111 Octreotide is a radioactive labeled peptide (small protein) that has affinity for Somatostatin receptors which exist almost exclusively on the cell surface of Neuroendocrine cancer cells. This agent in low dose (about 5.0 mCi) is used as a diagnostic imaging test to identify the locations of the Neuroendocrine tumors. Significantly higher doses such as 500 mCi of this agent has been shown to have therapeutic effects on these tumors.

Excel Diagnostics and Nuclear Oncology Center in collaboration with RITA Foundation, Baylor College of Medicine, and St. Luke’s Hospital started treating patients with this agent in August of 2005. The treatment was under FDA oversight and approved Investigational New Drug Application. The result of our treatments on first 32 patients with at least 2 cycles of treatment with 500 mCi In-111 Octreotide was very promising and was published in Cancer Biotherapy and Radiopharmaceuticals in 2008. As of today so many patients have received up to 4 cycles of this treatment with majority of the patients with previous progressive disease achieving stable disease and significant improvement in their clinical symptoms. For further information about this treatment and Insurance coverage for this therapy please contact Ms. Susan Cork at: scork@exceldiagnostics.com.

You can find more about the result of this therapy on the two articles that are published in 2008 and 2012 in the following links:

1-Safety and efficacy of radionuclide therapy with high-activity In-111 pentetreotide in patients with progressive neuroendocrine tumors.

2-Long-Term Survival, Toxicity Profile, and role of F-18 FDG PET/CT scan in Patients with Progressive Neuroendocrine Tumors Following Peptide Re-ceptor Radionuclide Therapy with High Activity In-111 Pentetreotide

Patients will be accepted for therapy according to the following inclusion and Exclusion criteria :

Inclusion Criteria

 1-Patients with biopsy proven malignancies which express the somatostatin receptor as demonstrated by significant uptake of Indium-111 pentetreotide during a diagnostic scan.  If possible, tumor tissue should be submitted for somatostatin receptor assay.

2- Patients must have received first line standard surgery, and/or chemotherapy and/or radiation therapy and/or Sandostatin therapy for neuroendocrine malignancy in the past and failed the therapy.

3-Patients must have evidence of residual multifocal active tumor. 

4-All patients must sign an informed consent indicating the awareness of the investigational nature of the studies involved.

5-All patients must have a Karnofski performance status of at least 60%.

6-Patients must be greater than 18 years of age.

7-Patients must have measurable and/or followable disease based on either clinical or radiologic exam.

8-Sensitivity to Indium-111 pentetreotide or any of its components is an absolute contraindication to participation in this trial.

9-An absolute contraindication is pregnancy as evidenced by the clinical condition, a positive pregnancy test (B-HCG or pelvic ultrasound).

10- If patients have received prior radionuclide therapy of the same product, there must be documented response to that therapy and/or residual active stable disease.

 

Exclusion Criteria

 1-Karnofsky performance status of 50% or less.

2-Patients who are unable to give informed consent.

3-Patients under 18 years of age.  There will be no upper age discrimination.

4-Patients who are pregnant or those potentially pregnant subjects not willing to practice effective contraceptive techniques during the study period.

5-Patients with renal insufficiency as defined by a calculated creatinine clearance (based on age, weight and  serum creatinine) of 39.9 ml/min or less.

Lutetium-177 Octreotate Therapy

Lutetium -177 Octreotate is another somatostatin receptor seeking agent that can detect neuroendocrine tumor cells throughout the body, attach to them and delivers therapeutic dose of radioactivity to the tumor. This targeted radionuclide therapy has shown significant therapeutic effect on previously progressive tumors. Following is the results of the treatment on several hundred patients performed at Erasmus Medical Center in Netherlands:

“From January 2000 until August 2006 1772 treatments with lutetium-octreotate were given to a sum of 504 patients. Most patients had neuroendocrine tumours. A preliminary analysis in 310 patients with so-called gastroenteropancreatic tumours was performed after obtaining all results after finishing the treatment. This showed a decrease in the size of the tumours in 46% of patients, stable disease in 35% and progression of the tumour despite treatment in 20%. A significant improvement of quality of life in those patients with tumour regression was also noted. The average duration of the effect of therapy was 40 months, calculated from the start of therapy. In addition, there are strong indications that patients treated with Lutetium-octreotate, on average, survive several years longer (3-6 years) than patients who did not get this treatment. ”

Other centers in Europe including Germany, Switzerland, Italy, Sweden and others have also reported very promising results on the effectiveness and safety of this treatment option.

We at Excel Diagnostics and Nuclear Oncology Center are pleased to announce that we will have this treatment available for our patients in the United States in mid October of 2010. Please refer to our press release on August 18, 2010 regarding this exciting news.

Following is some information for our patients regarding this treatment at our center:

“Our protocol calls for 4 treatments every 6-9 weeks. For the first therapy, patients should expect staying 2 weeks in Houston. For the subsequent therapies, only one week. During their stay in Houston, patients will undergo all the protocol required imaging studies. We have to repeat the Octreoscan even patient has done it recently, since we have to do dosimetry with the study. A list of these studies will be sent to the referring physicians prior to the patient arrival in Houston. Lab request will be sent to the patients by our office, so they can do them before coming to Houston.

There are low cost but safe and clean facilities within one mile from our center that are currently housing our Indium therapy patients. Average cost per night is around $ 75.00 per night.

We will need the following information to start the evaluation and registration:

  1. Patient demographics including patient contact and Insurance information.
  2. Pathology report of biopsy or surgical specimen.
  3. Recent Radiology imaging study reports.
  4. Recent Octreoscan report and preferably CD (Within one year is fine)
  5. Recent H&P including patient’s current medications.
  6. Recent labs including any marker studies.

We will have a brochure with all the necessary information ready for the patients and referring physicians in September of 2010. Please contact Excel clinical coordinators, Ms. Susan Cork at scork@exceldiagnostics.com for further information and registration for this therapy. ”

Information for referring physicians on Lu-177 Octreotate Therapy

Patients will be accepted for therapy according to the following inclusion and Exclusion criteria :

Inclusion Criteria

  1. Patients with biopsy proven Gastroenteropancreatic (GEP tumors including bronchial Carcinoid
  2. Presence of somatostatin-receptors on the know tumor lesions demonstrated by OctreoScan within 6 months of the first dose of radiolabeled Octreotate therapy. The uptake on the OctreoScan should be at least as high as normal liver uptake on planar imaging.
  3. Life Expectancy greater than 12 weeks.
  4. 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.
  5. Hemoglobin (Hgb) concentration ≥ 5.5 mmol/L (≥ 8.9 g/dL); WBC ≥ 2*109/L (2000/mm3); platelets ≥ 100*109/L (100*103/mm3).
  6. Total Bilirubin ≤ 3X UNL.
  7. Serum Albumin > 30g/L or serum albumin ≤ 30g/L but normal prothrombin time.
  8. All patients must have a Karnofski performance status of at least 60%
  9. 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

    1. Possible surgery with curative intent.
    2. Surgery, radiotherapy, chemotherapy or other investigational therapy within 3 months of the start of therapy.
    3. Patients with known brain metastases unless these metastases have been treated and stabilized for at least 6months 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.
    4. Uncontrolled congestive heart failure.
    5. Any subject who is taking concomitant medications which decrease renal function (such as amino-glycoside antibiotics).
    6. 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.
    7. 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 radiolabeled somatostatin analogues, or any subject receiving 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.
    8. 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 seeked for adequate further work-up.
    9. Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
    10. Prior radiation therapy to more than 25% of the bone marrow.
    11. 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.

Inclusion and exclusion criteria cycles 2-4

Exclusion criteria cycles 2-4: all exclusion criteria for cycle 1 apply

Inclusion criteria cycles 2-4:

  1. Serum creatinine ≤150 μmol/liter or 1.7 mg/dL, or a measured creatinine clearance (or measured GFR) of ≥ 50 mL/min. Should a 40% increase over the Cycle 1/ Baseline serum creatinine value occur during the course of treatment , with a concomitant decrease of over 40% in creatinine clearance as calculated from serum creatinine concentrations according to Cockroft’s method, patients must also have a measured creatinine clearance (or GFR) performed.
  2. Hemoglobin (Hgb) concentration ≥ 5.0 mmol/L (≥8.0 g/dL); WBC ≥ 2*109/L (2000/mm3); platelets ≥ 75*109/L (75*103/mm3).
  3. Total bilirubin ≤3 x ULN.
  4. Serum albumin > 30 g/L, or serum albumin ≤ 30 g/L but normal prothrombin time.
  5. Karnofski Performance Status ≥ 60.
Xofigo Therapy

 Xofigo® (radium Ra 223 dichloride) injection is indicated for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease.

For Important Safety Information about Xofigo Therapy please click the following link:

Xofigo Therapy Safety Information

More information for Physician: Please click the following Link:

Physician Information about Xofigo

Zevalin Therapy

 The ZEVALIN therapeutic regimen is used to treat patients with:

  • Recurring, low-grade or follicular B-cell NHL, after other anticancer drugs are no longer working.
  • Newly diagnosed follicular NHL following a response to initial anticancer therapy.

For Important Safety Information about Zevalin Therapy please click the following link:

 Zevalin Therapy Saftety Information

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Physician Information about Zevalin

Samarium Therapy

This drug is used to help relieve bone pain in some types of cancer that have spread to the bones.

For Important Safety Information about Samarium Therapy please click the following link:

Samarium Therapy Safety Information

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Physician Information about Samarium

Radioiodine Therapy for thyroid cancer

For Important Safety Information about Radioiodine Therapy please click the following link:

Radioiodine Therapy Safety Information

Radioactive Iodine for Hyperthyroidism

For Important Safety Information about this Therapy please click the following link:

Radioactive Iodine information