Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over Other 2006-1107 NCT00573677

Trial Description

Summary

Primary Objectives:

1. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of ABI-009.

2. To characterize the toxicities of ABI-009.

3. To determine the pharmacokinetic parameters for ABI-009 when given on a weekly schedule.

Secondary Objectives:

1. To identify predictors and pharmacodynamic markers of response to ABI-009.

2. To report anti-tumor activity of ABI-009 observed in this patient population.

3. To evaluate SPARC and other molecular biomarkers in tumor tissue and peripheral blood and their possible correlation with efficacy outcomes.

Further Study Information

The Study Drug:

ABI-009 is designed to bind to certain proteins, which may prevent or slow the growth of cancer cells.

Screening Tests:

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 and are to be performed within 28 days before your first dose of study drug. Laboratory evaluations must be done within 7 days before your first dose of study drug.

• Your medical history will be recorded, including any past cancer treatments.

• You will have a physical exam, including measurement of your height, weight, and vital signs (blood pressure, breathing rate, heart rate, and temperature).

• You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).

• You will be asked about any other medications you may be taking.

• Blood (about 2 tablespoons) will be drawn for routine tests and for a cholesterol test.

• You will have a Chest x-ray done (not required if a CT or MRI of chest is done).

• You will also have a computed tomography (CT), or magnetic resonance imaging (MRI) scan to measure the size of the tumor.

• You will also have a bone scan.

• You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

• Women who are able to have children must have a negative blood (about 1 teaspoon) pregnancy test.

• If required by your study doctor, you may be required to have a CT or MRI scan of your head.

Study Drug Dose Level:

If you are found to be eligible to take part in the study, you will begin receiving ABI-009. The dose you will receive will be based on how many participants have been enrolled before you, and on the safety data that is available. There will be 3 participants enrolled in each group. The first group of participants enrolled on this study will be given small doses of ABI-009. If no intolerable side effects are experienced, the next group of participants will be enrolled at a higher dose level. This process will continue until researchers find the highest tolerable dose of ABI-009 that can be given without intolerable side effects occurring.

Both you and your doctor will know what dose of the study drug you are receiving. If you experience any intolerable side effects, your dose level may be reduced to stop intolerable side effects from occurring, depending on what the study doctor thinks is best.

Study Drug Administration:

You will receive the study drug through a needle in your vein over 30 minutes on Days 1, 8, and 15 of each Cycle, followed by a week without treatment. Each 28 days is called a study "cycle".

Once the highest tolerable dose is reached, the dosing will be given every week, (Days 1, 8, 15, and 21) without a rest week.

Study Visits:

On Days 1, 8, and 15 before finding the highest tolerable dose, you will have the following tests and procedures performed:

• You will have a performance status evaluation.

• You will be asked about any other medications you may be taking, any procedures you may have had or will be having done, and any side effects you may be experiencing.

• You will have a physical exam, including measurement of weight.

• Your vital signs will be measured before you receive the study drug and at the end of the infusion.

• Blood (about 2 tablespoons) will be drawn for routine blood tests.

Once the highest tolerable dose is reached you will have the following tests and procedures performed:

• You will have a performance status evaluation.

• You will be asked about any other medications you may be taking, any procedures you may have had or will be having done, and any side effects you may be experiencing.

• You will have a physical exam, including measurement of weight.

• Your vital signs will be measured before you receive the study drug and at the end of the infusion.

• Blood (about 2 tablespoons) will be drawn for routine blood tests.

Pharmacokinetic Testing in Cycle 1:

During Cycle 1, you will have extra blood samples drawn for pharmacokinetic (PK) tests. PK testing measures the amount of study drug in the body at different time points.

Blood samples (about 1 teaspoon each time) will be drawn a total of 16 times for PK testing.

On Day 1 of Cycle 1, blood samples will be drawn just before the ABI-009 infusion begins, 15 minutes after the infusion begins, and 30 minutes after the infusion begins (right before the infusion ends). After the infusion ends, samples will be drawn at 15 minutes, 30 minutes, and at 1, 1.5, 2, 4, 6, and 8 hours later.

On Day 2 of Cycle 1, a blood sample will be drawn at 24 hours after the end of the Day 1 infusion.

On Day 3 of Cycle 1, a blood sample will be drawn 48 hours after the end of the Day 1 infusion.

On Day 4 of Cycle 1, a blood sample will be drawn 72 hours after the end of the Day 1 infusion.

On Day 5 of Cycle 1, a blood sample will be drawn 96 hours after the end of the Day 1 infusion.

On Day 8 of Cycle 1, a blood sample will be drawn 168 hours after the end of the Day 1 infusion.

Pharmacodynamic Testing in Cycle 1:

During Cycle 1, you will have extra blood samples drawn for pharmacodynamic (PD) tests. PD testing is used to look at how the level of study drug in your body may affect the disease.

Blood samples (about 1 ½ teaspoon each time) will be drawn a total of 4 times for PD testing.

On Day 1 of Cycle 1, a blood sample will be drawn just before the ABI-009 infusion begins. This blood will be drawn at the same time as the PK blood sample and will not require an additional needle stick.

On Day 2 of Cycle 1, a blood sample will be drawn at 24 hours after the end of the Day 1 infusion. This blood will be drawn at the same time as the PK blood sample and will not require an additional needle stick.

On Day 4 of Cycle 1, a blood sample will be drawn 72 hours after the end of the Day 1 infusion. This blood will be drawn at the same time as the PK blood sample and will not require an additional needle stick.

On Day 8 of Cycle 1, a blood sample will be drawn 168 hours after the end of the Day 1 infusion. This blood will be drawn at the same time as the PK blood sample and will not require an additional needle stick.

An additional 2 teaspoons of blood will be drawn to see if there is correlation between the circulating tumor cells and the effect of treatment at Baseline and on Day 1 of every other cycle of treatment and on the day imaging is performed (if the imaging day sample coincides with the every other cycle schedule, no additional blood sample will be required on that day). This blood will be drawn at the same time as the other blood samples and will not require an additional stick.

Every 12 weeks, you will have the following tests and procedures performed:

• Blood (about 2 tablespoons) will be drawn to check your cholesterol and triglyceride level.

• You will also have a CT scan, or MRI to check the status of the disease.

• If your doctor thinks it is necessary, you will also have a bone scan.

Length of Study:

You may remain on study for as long as you are benefitting. You will be taken off study if any of the following occurs:

• Your disease gets worse.

• You develop side effects that are unacceptable in the opinion of your study doctor.

• You refuse to continue receiving the study drug treatment.

• You begin another drug or therapy to treat your cancer.

• Your doctor decides that it is in your best interest to stop taking part in the study.

End-of-Study Visit:

Once you are off-study, or if the disease gets worse or intolerable side effects occur, or if you decide to withdraw your participation for any reason, you will be asked to come into the clinic for an end-of-study visit within 28 days after your last dose of the study drug. At the end-of-study visit, you will have the following tests and procedures performed:

• You will receive a physical exam, including measurement of your weight and vital signs.

• You will have a performance status evaluation.

• You will be asked about any other medications you may be taking and any procedures you may have had or are having done, and any side effects you may be experiencing.

• You will also have a computed tomography (CT), or magnetic resonance imaging (MRI) scan to measure the size of the tumor.

• If necessary, you will also have a bone scan.

• You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

• Blood (about 2 tablespoons) will be drawn for routine tests and for a cholesterol and triglyceride tests.

Follow-Up Visit(s):

All participants who are taken off the study will be followed by their doctor, to check for the development of any side effects and/or until any side effects you have now get better.

This is an investigational study. ABI-009 is not FDA approved or commercially available. It has been authorized for use in research only. Up to 42 patients will take part in this study. All participants will be enrolled at M. D. Anderson.

Eligibility Criteria

Inclusion Criteria:

• Male and female patients with histologically or cytologically confirmed diagnosis of cancer which is not amenable to curative therapy. For the purpose of this study, advanced disease will be defined as metastatic disease or locally advanced disease that is surgically unresectable and considered unmanageable with standard therapies such as radiation or systemic therapies.

• Patients with advanced non-hematologic malignancies for whom no standard therapy exists.

• Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, pleural effusion, ascites, or lesions which do not fulfill RECIST criteria for metastatic disease)

• Off all therapy (inclusive of investigational therapies) for at least 4 weeks prior to study drug administration OR off all daily or weekly therapy (inclusive of investigational therapies) for at least 2 weeks prior to study drug administration and without any side effects associated with these therapies.

• Female patients of child-bearing potential must have a negative serum pregnancy test within 7 days prior to first study drug administration and must agree to the use of a physical method of non-hormonal contraception while patient is participating in this study and at least 6 months following discontinuation of study drug.

• Female patients who are postmenopausal must have 12 months of amenorrhea, surgically sterile, or must agree to the use of a physical method of non-hormonal contraception while patient is participating in this study and at least 6 months following discontinuation of study drug.

• Male patients must be surgically sterile or agree to the use of a barrier method of contraception while patient is participating in this study and at least 6 months following discontinuation of study drug.

• Life expectancy of >/= 3 months.

• ECOG Performance Status of 0-2.

• Patients must be able to provide informed consent indicating knowledge of his/her disease process, the investigational nature of the therapy, alternatives, benefits, and risks including potential side effects.

• Age >/= 18 years of age.

• No major surgery within 4 weeks before treatment with ABI-009. (A biopsy is not considered major surgery).

• No chemotherapy, hormonal therapy, immunotherapy or radiotherapy within 4 weeks before treatment with ABI-009 (6 weeks for previous treatment with nitrosoureas, mitomycin, or extensive radiotherapy) and no immunosuppressive agents within 3 weeks before study entry (except corticosteroids used as antiemetics).

• No immunosuppressive agents within 3 weeks before study entry (except corticosteroids used as antiemetics).

• Required Initial Laboratory Data: Hemoglobin >/= 9.0 g/dL, WBC >/= 3,000/microliter, ANC >/= 1,500/microliter, Platelet count >/= 100,000/microliter, Total Bilirubin </= ULN, SGOT (AST) </= 1.5 x upper limits of normal, SGPT (ALT) </= 1.5 x upper limits of normal, Serum Cholesterol </= 350 mg/dL, Serum Triglyceride </= 300 mg/dL.

• Adequate renal function with serum creatinine </= 1.5 mg/dL and/or creatinine clearance (Cockcroft formula) >/= 60 mL/min.

• No active alcohol abuse, drug addiction, or psychotic disorders.

• No known concomitant genetic or acquired immunosuppressive diseases (such as AIDS).

• If obese, a patient must be treated with doses calculated using his/her actual BSA (The physician must be comfortable treating at the full BSA dose regardless of BSA).

Exclusion Criteria:

• Pregnant or nursing women.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition including macrolide (e.g. azithromycin, clarithromycin, dirithromycin, and erythromycin) and ketolide antibiotics.

• Patients have not recovered from adverse affects of radiation therapy or investigational agent within previous 28 days.

• Uncontrolled intercurrent illness that in the opinion of the investigator would limit compliance and tolerance to study requirements (eg: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, uncontrolled hypertension, coronary artery disease, or psychiatric illness/social situations).

• Patients with known brain metastases or leptomeningeal tumor involvement should be excluded from this clinical trial because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

• Receiving any of the following: concomitant antitumor therapy or inhibitors of CYP3A4.

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Ana Gonzalez-Angulo, MD

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00573677
Information obtained from ClinicalTrials.gov on July 16, 2008