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

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoid Tumor
• Intervention / Treatment: Drug: Panzem (2-methoxyestradiol) NCD, Avastin (Bevacizumab)

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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); Panzem NCD 1,000 mg, four times daily for 28 consecutive days bevacizumab 5 mg/kg intravenous bolus on Day 1 and Day 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: CASI Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Matthew H. Kulke, M.D., Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: May 18, 2006
• First Submitted That Met QC Criteria: May 19, 2006
• First Posted (Estimate): May 22, 2006

Study Record Updates

• Last Update Posted (Estimate): March 10, 2010
• Last Update Submitted That Met QC Criteria: March 9, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Carcinoid Tumor; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; 2-Methoxyestradiol
• Other Study ID Numbers: ME-CLN-002