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

(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).

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