A Combination Study to Determine the Safety and Efficacy of Panzem NCD With Avastin in Metastatic Carcinoid Tumors

Study Overview
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Brief Summary
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This single center, open-label study will evaluate the safety and efficacy of Panzem (2-methoxyestradiol, 2ME2) Nanocrystal Dispersion (NCD) administered orally with recombinant human monoclonal antibody against vascular endothelial growth factor (bevacizumab) administered intravenously, in patients with locally advanced or metastatic carcinoid tumors.

Official Title
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A Phase 1-2 Safety and Efficacy Study of Panzem Nanocrystal Colloidal Dispersion Administered Orally in Combination With rhuMAb VEGF (Bevacizumab) in Patients With Locally Advanced or Metastatic Carcinoid Tumors

Conditions
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Carcinoid Tumor

Intervention / Treatment
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* Drug: Panzem (2-methoxyestradiol) NCD, Avastin (Bevacizumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented locally unresectable or metastatic carcinoid neuroendocrine tumor Measurable disease, according to RECIST, with at least one lesion that is unidimensionally measurable by conventional techniques to be greater than or equal to 2 cm in diameter, or by spiral CT to be greater than or equal to 1 cm in diameter 18 years or older Laboratory data to include (next 7 bullet points): Aspartate aminotransferase(AST)and alanine aminotransferase (ALT)less than 2.5 times the upper limit of normal (less than 5 times upper limit of normal if liver metastasis present) Total bilirubin less than or equal to 2 mg/dL Serum creatinine less than or equal to 1.5 mg/dL Total white blood cell count greater than 3,500/mm3 Absolute neutrophil count greater than or equal to 1,500/mm3 International normalized ratio less then or equal to 1.5 Platelets greater than or equal to 100,000/mm3 Agree to use effective contraceptive methods Have an ECOG performance status of less than 2 Life expectancy of greater than 12 weeks Ability to understand the requirements of the study, have provided written consent, and agree to abibe by the study restrictions Exclusion Criteria: Pregnant or nursing, or refusal to use appropriate birth control An active infection Have a history of myocardial infarction or angina pectoris/angina equivalent in the last 12 months (the patient may be on antianginal medications if the symptoms can be fully controlled), or have uncontrolled congestive heart failure Have apparent central nervous system metastasis or carcinomatous meningitis Have had any active cancer in addition to the carcinoid tumor within the last 5 years, with the exception of superficial skin cancer Be receiving concurrent treatment with therapeutic doses of any anticoagulant including all forms of heparin and Coumadin Have current or a history of severe bleeding Uncontrolled / severe hypertension Previous history of nephrotic syndrome Urine protein: creatinine ratio greater than or equal to 1.0 at screening Have received radiotherapy or chemotherapy within the previous 4 weeks Participated in any clinical trial involving conventional or investigational drugs or devices within the previous 4 weeks Have had major surgery within 4 weeks or plan to undergo elective surgery during treatment Additional uncontrolled serious medical condition or psychiatric illness Have any condition that is likely to interfere with regular follow-up

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Panzem NCD will be dosed orally at a level of 1,000 mg, four times daily for 28 consecutive days and bevacizumab will be administered at a dose of 5 mg/kg as an intravenous bolus on Day 1 and Day 15 of the Treatment Period | Drug: Panzem (2-methoxyestradiol) NCD, Avastin (Bevacizumab)<br>* Panzem NCD 1,000 mg, four times daily for 28 consecutive days bevacizumab 5 mg/kg intravenous bolus on Day 1 and Day 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of Panzem NCD administered orally in combination with intravenous infusion of bevacizumab by evaluation of the frequency and severity of treatment emergent adverse events |  | Approximately monthly | 
| To evaluate the objective tumor response rate by radiographic means using Response Evaluation Criteria in Solid Tumors |  | Approximately every 8 weeks | 
| To determine the overall survival of patients with locally advanced or metastatic carcinoid tumors administered oral Panzem NCD in combination with intravenous infusion of bevacizumab |  | Approximately every 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the progression-free survival of patients with locally advanced or metastatic carcinoid tumors administered oral Panzem NCD in combination with intravenous infusion of bevacizumab |  | Approximately every 3 months | 
| To monitor the steady-state trough plasma levels of 2ME2 following 28-day dosing cycles of Panzem NCD when administered orally in combination with intravenous infusion of bevacizumab |  | Approximately monthly |