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

NCT00328497 | Completed Phase 2

• 1 other identifier: ME-CLN-002
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Carcinoid Tumor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• 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

Study Arms (1)

1

EXPERIMENTAL

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)

Interventions

Panzem (2-methoxyestradiol) NCD, Avastin (Bevacizumab) DRUG

Panzem NCD 1,000 mg, four times daily for 28 consecutive days bevacizumab 5 mg/kg intravenous bolus on Day 1 and Day 15

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CASI Pharmaceuticals, Inc.: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Carcinoid Tumor

Interventions

2-Methoxyestradiol; Bevacizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Matthew H. Kulke, M.D.

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 18, 2006
• First Posted: May 22, 2006
• Study Start: May 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2009
• Last Updated: March 10, 2010

Record last verified: 2010-03

Locations

US (1)