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

Carcinoid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00328497
• Other study ID #: ME-CLN-002
• Status: Completed
• Phase: Phase 2
• First received: May 18, 2006
• Last updated: March 9, 2010
• Start date: May 2006
• Est. completion date: December 2009

Study information

• Verified date: March 2010
• Source: CASI Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoid Tumor
• Neuroendocrine Tumors

Intervention

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

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
CASI Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	To evaluate the objective tumor response rate by radiographic means using Response Evaluation Criteria in Solid Tumors		Approximately every 8 weeks	No
Primary	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	No
Secondary	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	No
Secondary	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	Yes