Official Title: “Phase I Dose-Finding Pilot Study of the Safety and Tolerability of Olanzapine in Patients With Advanced Cancer and Weight Loss”

Objectives:

1.1. Primary:

1. The primary objective is to define the safety and maximum tolerated dose (MTD) of Olanzapine in patients with weight loss and cachexia secondary to advanced cancer.

1.2. Secondary:

1. To perform a preliminary assessment of the metabolic profile changes in patients with advanced cancer treated at different doses of Olanzapine.

2. To outline the nutritional status and performance status changes of patients treated at different doses of Olanzapine.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2010

Olanzapine is approved for the treatment of schizophrenia and bipolar disorder. However, patients who have received this drug for these reasons have also experienced weight gain.

Further studies in patients with cancer showed an improvement in appetite, a decrease in nausea, and a control of flushing (feeling of warmth) and sweating.

Before you can start receiving the study drug, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a complete physical exam; your weight will be measured; and you will be asked questions about your nutrition, how well you are able to move about, and how you feel emotionally.

If you are found to be eligible to take part in this study and before you receive your first dose of Olanzapine, you will have routine blood tests (about 2 teaspoons). You will be asked a series of questions about your nutrition and how well you are able to perform daily activities. These questions should take about 20 minutes to answer. Your answers will help the study doctor decide if the study drug is helping you gain weight and if your weight gain is helping you feel better. You will also have an electrocardiogram (ECG - a test to measure the electrical activity of the heart). Women who are able to have children must have a negative blood pregnancy test (about 1 teaspoon).

After the tests above are completed, you will begin receiving Olanzapine. The study drug will be taken by mouth once daily at bedtime for 28 days in a row. Seven different doses of the drug are planned with 6 patients enrolled on each level. The level you are assigned to will depend on when you are enrolled on this study. All participants will begin taking the same strength of the study drug. This will gradually increase about every 3 - 14 days until you reach the highest strength of the study drug for the dose level to which you are assigned.

About every 2 weeks during this study for the first month and then about once a month thereafter, you will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), and your medical history will be discussed. You will also have routine blood tests (about 2 teaspoons) to check your general health.

You will continue to receive the highest strength of the study drug for the dose level to which you are assigned for about 4 months unless you have intolerable side effects or if your weight continues to decrease. The study doctor will decide if you should continue receiving Olanzapine after 4 months.

This is an investigational study. The FDA has approved Olanzapine for mental health diseases (schizophrenia, acute mania, and bipolar disorder). Its use in preventing weight loss is experimental.Up to 57 patients will take part in this study. All will be enrolled at M. D.

Anderson.

Intervention(s) in this Clinical Trial

• Drug: Olanzapine
  • 2.5 mg by mouth (PO) Daily x 28 days, increasing about every 3-14 days in increments of 2.5-5 mg until the designated dose for that cohort is reached.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Olanzapine

Primary Measures

• Highest tolerable dose of the drug Olanzapine that can be given to patients with advanced cancer who are experiencing weight loss.
  • Time Frame: 4 Years
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Patient with confirmed advanced cancer.
• 2. Patients with decreased daily caloric intake (<1500 Calories/day), or with a weight loss equivalent to 10% of body weight over six months
• 3. Patients should be able to have an oral intake and not be dependant on tube feeding, or have significant oropharyngeal obstruction, gastro-duodenal obstruction, or oral mucosal inflammation interfering with oral intake. Patients who have undergone gastro-jejunal bypass, esophagectomy, or total gastrectomy will be excluded.
• 4. ECOG performance status 2 or less.
• 5. Normal organ function: Creatinine less or equal to 2 times ULN; Bilirubin less or equal 2.5 times ULN
• 6. Ability to understand and the willingness to sign written informed consent.
• 7. Patients receiving concurrent chemotherapy or radiation therapy are eligible for enrollment.
• 8. Expected life expectancy of at least 3 months.

Exclusion Criteria:

• 1. Uncontrolled concurrent illness such as unstable angina, myocardial infarction in the preceding month, neutropenic fever, shock, symptomatic decompensate congestive heart failure, or congestive Heart Failure of NYHA III or IV, active internal bleeding.
• 2. Hypersensitivity to olanzapine, or history of dyskinesia or extrapyramidal syndrome on atypical neuroleptic.
• 3. Concurrent treatment with any atypical antipsychotic such as clozapine, risperidone, olanzapine, quetiapine, ziprasidone or aripiprazole
• 4. History of clozapine-induced agranulocytosis because patients will be at increased risk for neutropenia with Olanzapine.
• 5. Major surgery within four weeks of study start day.
• 6. Uncontrolled diabetes mellitus
• 7. Uncontrolled seizure disorder (any episode in the previous 4 weeks).
• 8. Pregnant and Nursing women.
• 9. Patients may not have started an appetite stimulant such as megace or therapeutic dose of steroids (superior or equal to an equivalent of 4 mg dexamethasone/day), or increased the dose of such medication (by more than 50%) in the previous week.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Razelle Kurzrock, MD Principal Investigator U.T.M.D. Anderson Cancer Center  

Overall Contact: Razelle Kurzrock, MD 713-794-5188 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00489593

Study ID Number: 2005-0620

ClinicalTrials.gov Identifier: NCT00489593

Health Authority: United States: Institutional Review Board

UT MD Anderson Cancer Center