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Chemotherapeutic Agent ToxicityPhase 1NCT01562301

Sublingual Anvirzel in Advance Non-Small Cell Lung Cancer (NSCLC)

A Phase 1 study testing Carboplatin, Docetaxel and Anvirzel in people with Chemotherapeutic Agent Toxicity and Lung Cancer, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The goal of this clinical research study is to find the highest tolerable dose of Anvirzel (Nerium Oleander) that can be given to lung cancer patients receiving standard therapy with carboplatin and docetaxel. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chemotherapeutic Agent Toxicity, Lung Cancer
What is being tested?
Carboplatin, Docetaxel and Anvirzel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2014to Jun 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed diagnosed advanced non-small cell lung cancer (Stage IIIB and IV) and be scheduled to receive four cycles of carboplatin and docetaxel chemotherapy.
  • Newly diagnosed or previously treated patient with NSCLC. Previously treated patients are allowed to have any previous chemotherapy for the treatment of NSCLC.
  • Age >18 years
  • ECOG performance status < or =2 (Karnofsky > or = 60%)
  • Life expectancy of greater than 6 months
  • Patients must have normal organ and marrow function as defined below: - leukocytes > or = 3,000/mcL - absolute neutrophil count > or = 1,500/mcL - platelets > or = 100,000/mcL - total bilirubin within normal institutional limits - AST(SGOT)/ALT(SGPT) < or = 2.5 X institutional upper limit of normal - creatinine within normal institutional limits OR - creatinine clearance > or = 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
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  • Negative serum or urine pregnancy test in women of child-bearing potential
  • Scheduled to begin carboplatin and docetaxel chemotherapy in the next 30 days
  • The effects of Anvirzel on the developing human fetus are unknown. For this reason, 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cardiac glycosides
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP 3A4 are ineligible
  • 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
  • Pregnant or breastfeeding women
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Anvirzel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
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  • Uncontrolled or significant cardiovascular disease, including: • Myocardial infarction within 6 months • Uncontrolled angina within 6 months • Newly diagnosed congestive heart failure within 6 months, defined as NYHC-II or currently uncontrolled congestive heart failure • 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 (> 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 • Heart rate < 50 beats/minute or sustained heart rate > 110 on pre-entry electrocardiogram • Newly diagnosed atrial fibrillation within 6 months or currently uncontrolled atrial fibrillation • Uncontrolled hypertension defined as sustained blood pressure of >/= 140/90mm Hg
  • Current use of a pacemaker
  • Patients using or scheduled to use bevacizumab during study period
  • Current use of cardiac glycoside

About this study

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

The goal of this clinical research study is to find the highest tolerable dose of Anvirzel (Nerium Oleander) that can be given to lung cancer patients receiving standard therapy with carboplatin and docetaxel. Researchers also want to learn what effect Nerium Oleander may have in combination with carboplatin and docetaxel.

Read the detailed description

Study Drug Administration:

If you are eligible and agree to take part in the study, you will be assigned to a dose level of nerium oleander based on when you join this study. Up to 5 dose levels of nerium oleander will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of nerium oleander is found.

You will take nerium oleander by mouth by placing it under your tongue. You should hold the nerium oleander under your tongue for 3 minutes before swallowing. It is very important for you to hold the nerium oleander under your tongue for 3 full minutes. Holding it under your tongue for 3 minutes before swallowing helps your body to take in the highest amount of the drug that you can receive. If you hold the nerium oleander under your tongue for less than 3 minutes, your body will not receive as much of the study drug and may not possibly benefit as much. You will take nerium oleander 3 times a day while participating in this study. Nerium oleander should be taken on an empty stomach or at least 15 minutes before any large meal, to help your body take in as much of the drug as possible.

Study Visits:

Each of your chemotherapy cycles are 21 days.

Each week while on study, you will complete the questionnaire about any symptoms you may be having. It should take about 5 minutes to complete it each time.

Cycle 1:

On Day -7 (7 days before you start chemotherapy):

  • You will complete the questionnaire about your physical and mental health. It should take about 5 minutes to complete it.
  • Blood (about 2 teaspoons each time) will be drawn 6 times over 8 hours for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points.
  • Blood (about 6 teaspoons) will be drawn to learn if the study drug is reducing inflammation.
  • Blood (about 2 teaspoons) will be drawn to test the effect of the study drug on your immune system.

On Day -6, blood (about 2 teaspoons each time) will be drawn 1 time for PK testing.

On Day 1 (the day you start chemotherapy):

  • You will be asked about any symptoms you may be having or drugs you may be taking.
  • You will have a physical exam, including measurement of weight and vital signs.
  • Your performance status will be recorded.
  • You will complete the questionnaire about your physical and mental health.
  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • Blood (about 2 teaspoons each time) will be drawn 6 times over 8 hours for PK testing.
  • Blood (about 6 teaspoons) will be drawn to learn if the study drug is reducing inflammation.
  • Blood (about 2 teaspoons) will be drawn to test the effect of the study drug on your immune system.
  • You will have an EKG.

On Day 2:

  • Blood (about 2 teaspoons) will be drawn for PK testing.
  • Blood (about 6 teaspoons) will be drawn to learn if the study drug is reducing inflammation.
  • Blood (about 2 teaspoons) will be drawn to test the effect of the study drug on your immune system.

On Day 8 (+/- 2 days):

  • Blood (about 6 teaspoons) will be drawn to learn if the study drug is reducing inflammation.
  • Blood (about 2 teaspoons) will be drawn to test the effect of the study drug on your immune system.

On Day 1 of Cycles 2-3:

  • You will be asked about any symptoms you may be having or drugs you may be taking.
  • You will have a physical exam, including measurement of weight and vital signs.
  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • Your performance status will be recorded.
  • You will have an EKG.
  • You will complete the questionnaire about your physical and mental health.
  • On Day 1 of Cycle 3 only, you will have a CT scan to check the status of the disease.

On Day 1 of Cycle 4:

  • You will be asked about any symptoms you may be having or drugs you may be taking.
  • You will have a physical exam, including measurement of weight and vital signs.
  • You will complete the questionnaire about your physical and mental health.
  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • Your performance status will be recorded.
  • You will have an EKG.
  • Blood (about 2 teaspoons each time) will be drawn 6 times over 8 hours for PK testing.
  • Blood (about 6 teaspoons) will be drawn to learn if the study drug is reducing inflammation.
  • Blood (about 2 teaspoons) will be drawn to test the effect of the study drug on your immune system.

On Day 2 of Cycle 4:

  • Blood (about 2 teaspoons) will be drawn for PK testing.

On Day 8 and Day 21 of Cycle 4 (+/- 2 days):

  • Blood (about 6 teaspoons) will be drawn to learn if the study drug is reducing inflammation.
  • Blood (about 2 teaspoons) will be drawn to test the effect of the study drug on your immune system.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest or up to 4 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visit.

End-of-Dosing Visit:

After your last dose of study drug, you will return to the clinic. The following tests and procedures will be performed:

  • You will be asked about any symptoms you may be having or drugs you may be taking.
  • You will have a physical exam, including measurement of weight and vital signs.
  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • You will have an EKG.
  • You will have a CT scan to check the status of the disease.
  • You will complete both questionnaires.

Follow-Up Visit:

About 30 days after your last dose of study drug, the following tests and procedures will be performed:

  • You will be asked about any symptoms you may be having or drugs you may be taking.
  • You will have a physical exam, including measurement of weight and vital signs.
  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • You will have an EKG.
  • You will complete both questionnaires.

This is an investigational study. Nerium oleander is not FDA approved or commercially available. Its use in this study is considered investigational.

Up to 36 participants will be enrolled in this study. All will take part at MD Anderson.

Being tested
Carboplatin, Docetaxel, Anvirzel, Questionnaires
Keywords
chemotherapeutic agent toxicity, recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, carboplatin, Paraplatin, docetaxel, Taxotere, Anvirzel, nerium oleander, Advanced Non-Small Cell Lung Cancer, NSCLC
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Paraplatin

    AUC 6 by vein 7 days after Anvirzel administration in a 21 dayc cycle.

  • DocetaxelDrug

    Also called Taxotere

    75 mg/m2 by vein 7 days after Anvirzel administration in a 21 day cycle.

  • AnvirzelDrug

    Also called Nerium oleander

    Starting Cohort Dose: 6 mg/m2 given 3 times a day administered sublingually for a 21 day cycle.

    Expansion Cohort Starting Dose: Maximum tolerated dose from

  • QuestionnairesBehavioural

    Also called Surveys

    Questionnaire completion regarding physical and mental at baseline, 7 days before chemotherapy, day 1 of chemotherapy, day 1 of cycles 2, 3, and 4, and at end of dosing visit.

Study groups in NCT01562301
Study groupRoleWhat they receive
Anvirzel + Carboplatin + DocetaxelExperimentalAnvirzel administered sublingually. A total of five dose cohorts evaluated (6, 12, 24, 36, 48 mg/m2/day; SL divided into 3 doses given every 8 hrs) with 3 patients per cohort. Patients receive the assigned dose (2, 4, 8, 12, or 16 mg/m2) of Anvirzel three times a day throughout each cycle for a total of 4 cycles of chemotherapy. Cycles occur every 21 days. Patients start with an AUC of 6 for Carboplatin and 75mg/m2 for docetaxel, and on subsequent cycles, modifications at the discretion of the treating team. Questionnaire completion regarding physical and mental at baseline, 7 days before chemotherapy, day 1 of chemotherapy, day 1 of cycles 2, 3, and 4, and at end of dosing visit.
Receives: Drug: Carboplatin; Drug: Docetaxel; Drug: Anvirzel; Behavioral: Questionnaires

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of sublingual (SL) dosing of Anvirzel in combination with chemotherapy

    Measured: 21 Day Cycle

  2. Pharmacokinetics of carboplatin and docetaxel when administered concurrently with SL Anvirzel

    Pharmacokinetic studies evaluate plasma concentrations over a 24 hour period prior to administration of chemotherapy, using high performance liquid chromatographic and electron ion-spray mass spectrometry

    Measured: 24 hours

Secondary outcomes (4)

  1. Anti-inflammatory effects of SL Anvirzel during carboplatin and docetaxel chemotherapy

    Measured: Up to four 21 day cycles (84 days)

  2. Immunomodulatory effects of SL Anvirzel during carboplatin and docetaxel chemotherapy

    Measured: Up to four 21 day cycles (84 days)

  3. Symptoms and quality-of-life outcomes based on MDASI-LC and SF-12 scores

    Measured: Up to four 21 day cycles (84 days)

  4. Grade 3-4 toxicities at each course according to NCI Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0

    Measured: Up to four 21 day cycles (84 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2012 (estimated)
  2. Study startJun 2014
  3. Primary completionJun 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01562301
Sponsor's protocol ID
2011-0147
Other IDs
MDA-2011-0147, CDR0000728644, NCI-2012-00709
Status last verified
Jun 2015
First submitted
21 Mar 2012
Last updated
8 Jun 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carboplatin, Docetaxel and Anvirzel in people with Chemotherapeutic Agent Toxicity and Lung Cancer, run by M.D. Anderson Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of sublingual (SL) dosing of Anvirzel in combination with chemotherapy (time frame: 21 Day Cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01562301.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2015.

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