Anvirzel

Phase I Study of Oleandrin (Nerium Oleander Extract) in Combination With Carboplatin and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Oleandrin (Nerium Oleander) in Combination With Carboplatin and Docetaxel in Treating Patients With Advanced Non-Small Cell Lung Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs
Phase I Biomarker/Laboratory analysis, Supportive care Approved-not yet active 18 and over NCI MDA-2011-0147
2011-0147, NCT01562301
Objectives

Primary Objective

I.To determine the maximum-tolerated dose (MTD) of sublingual (SL) dosing of oleandrin (nerium oleander; Anvirzel) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy.
II.To evaluate the pharmacokinetics of carboplatin and docetaxel when administered concurrently with SL Anvirzel.
Secondary Objective

I.To evaluate the anti-inflammatory and immunomodulatory effects of SL Anvirzel during carboplatin and docetaxel chemotherapy in patients with advanced NSCLC.
II.To evaluate symptoms and quality-of-life outcomes, the incidence of grade 3-4 toxicities, dose reductions, dose delays, and completion of scheduled carboplatin and docetaxel chemotherapy with SL Anvirzel in patients with advanced NSCLC.
Entry Criteria

Disease Characteristics:

•Patients must have histologically or cytologically confirmed diagnosed non-small cell lung cancer (NSCLC) and be scheduled to receive four courses of carboplatin and docetaxel chemotherapyScheduled to begin carboplatin and docetaxel chemotherapy in the next 30 days

•Newly diagnosed or previously treated patient with NSCLC; previously treated patients are allowed to have any previous chemotherapy for the treatment of NSCLC

Prior/Concurrent Therapy:

•See Disease Characteristics
•No patients receiving any other investigational agents
•Patients receiving any medications or substances that are inhibitors or inducers of CYP 3A4 are ineligible
•No patients using or scheduled to use bevacizumab during study period
•No current use of cardiac glycoside

Patient Characteristics:

•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
•Life expectancy of greater than 6 months
•Leukocytes ≥ 3,000/mcL
•Absolute neutrophil count ≥ 1,500/mcL
•Platelets ≥ 100,000/mcL
•Total bilirubin within normal institutional limits
•Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 times institutional upper limit of normal
•Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
•Negative serum or urine pregnancy test in women of child-bearing potential
•Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
•Ability to understand and the willingness to sign a written informed consent document
•No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cardiac glycosides
•No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
•Not pregnant or breastfeeding
•HIV-positive patients on combination antiretroviral therapy are ineligible
•No uncontrolled or significant cardiovascular disease, including:A myocardial infarction within 6 months
Uncontrolled angina within 6 months
Congestive heart failure within 6 months, defined as New York Heart Classification II (NYHC-II)
Diagnosed or suspected congenital long QT syndrome
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes); prolonged QTc interval on pre-entry electrocardiogram (EKG) (> 450 msec); if the automated reading is prolonged (i.e., > 450 msec), the EKG should be manually over-read
Any history of second or third degree heart block (may be eligible if currently have a pacemaker)
Heart rate < 50 beats/minute OR sustained heart rate > 110 beats/minute on pre-entry EKG
Uncontrolled hypertension

Expected Enrollment

30Outcomes

Primary Outcome(s)
MTD of SL dosing of Anvirzel in combination with chemotherapy
Pharmacokinetics of carboplatin and docetaxel when administered concurrently with SL Anvirzel

Secondary Outcome(s)
Anti-inflammatory effects of SL Anvirzel during carboplatin and docetaxel chemotherapy
Immunomodulatory effects of SL Anvirzel during carboplatin and docetaxel chemotherapy
Symptoms and quality-of-life outcomes based on MDASI-LC and SF-12 scores
Grade 3-4 toxicities at each course according to NCI CTCAE version 4.0
Dose reduction and delays at each course

Outline

This is a dose-escalation study of oleandrin (nerium oleander extract).

Patients receive oleandrin sublingually (SL) 3 times daily (TID) on days -7 to 0 of course 1 and then throughout each course of carboplatin IV and docetaxel IV. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients complete the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) and the quality-of-life (SF-12) questionnaires at baseline and periodically during treatment.

Plasma and peripheral blood mononuclear cell samples are collected at baseline and periodically during treatment for biomarker, pharmacokinetic, and pharmacodynamic studies.

After completion of study treatment, patients are followed up for 4 weeks.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Richard Lee, MD, FACP, Principal investigator Ph: 713-745-2889; 800-392-1611

Registry Information

Official Title A Phase I Study of the Combination of Carboplatin, Docetaxel, and Increasing Doses of Sublingual Anvirzel (Nerium Oleander) in Advance Non-Small Cell Lung Cancer

Trial Start Date 2012-05-01 (estimated)

Trial Completion Date 2013-05-01 (estimated)

Registered in ClinicalTrials.gov NCT01562301

Date Submitted to PDQ 2012-03-08

Information Last Verified