Phase II Study of Tesetaxel in Metastatic Melanoma

The goal of this clinical research study is to learn if tesetaxel can help to control metastatic melanoma. The safety of this drug will also be studied.

The Study Drug:

Tesetaxel is designed to block cancer cells from dividing, which may cause them to die.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. If you have recently had any of these tests or procedures, the study doctor may decide that you do not need to repeat them. The following tests and procedures will be performed within 28 days before your first dose of study drug:

• Your medical history, including any side effects you may have had and any drugs you have taken or may be taking, will be recorded.
• You will have a physical exam, including measurement of your height and weight.
• You will be asked about whether you are able to swallow capsule forms of drug.
• You will have a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the head to check for brain metastasis.
• You will have a CT scan of the chest, stomach, and hip areas.
• Photographs of any melanoma on your skin will be taken. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are lesions on your face.

The following tests and procedures will be performed within 7 days before your first dose of study drug:

• Your medical history, including any side effects you may have had and any drugs you may be taking, will be recorded.
• You will be asked how well you are able to perform the normal activities of daily living (performance status).
• Blood( about 2 teaspoons) will be drawn for routine tests and to test how long it takes your blood to clot.
• Urine will be collected for routine tests.
• You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).
• Women who are able to become pregnant must have a negative blood (about 1 teaspoon) pregnancy test.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take tesetaxel capsules in the morning with water on Day 1 of each 21-day study cycle. You will not be allowed to eat or drink anything except water from midnight the night before the dose until 4 hours after taking tesetaxel.

Before you take tesetaxel, you will receive drugs to prevent nausea and vomiting. The study doctor will discuss this with you. If you have a rash or allergic reaction, you may be receive an antihistamine and/or corticosteroid. If you develop a low number of white blood cells or red blood cells, you may be given growth factor drugs or receive transfusions. These drugs may be given by mouth or vein.

Study Visits:

On Day 1 of all Cycles:

-Your medical history, including any side effects you may have had and any drugs you may be taking, will be recorded.

On Day 9 (+/- 1 day) and again on Day 20 (+/- 2 days) of all Cycles:

• Any side effects you may have had and any drugs you may be taking will be recorded.
• Blood (about 2 teaspoons) will be drawn for routine tests.

Within 5 days before the start of cycles 3, 5, 7 and every other cycle thereafter:

• You will have a CT scan of the chest, stomach, and hip areas.
• Photographs of any melanoma on your skin will be taken.
• Any side effects you may have had and any drugs you may be taking will be recorded.

After the last dose of tesetaxel, blood (about 2 teaspoons) will be drawn for routine tests.

Within 3 weeks after the last dose of tesetaxel:

• You will have a CT scan of the chest, stomach, and hip areas.
• Photographs of any melanoma on your skin will be taken.
• Any side effects you may have had and any drugs you may be taking, will be recorded.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

Follow-Up Visits:

If the melanoma does not get worse while you are on study, you will have visits every 2 months for up to 12 months after your first dose of study drug. At these visits:

• You will have a CT scan of the chest, stomach, and hip areas.
• Photographs of any melanoma on your skin will be taken.
• Any side effects you may have had and any drugs you may be taking, will be recorded.
• You will be asked about any treatment you may be receiving.

If the disease gets worse while you are on study, you will have follow up phone calls every 2 months for up to 12 months after your first dose of study drug. During these calls, you will be asked how you are feeling and about any therapy you are receiving. These calls should take about 5 minutes.

Additional Information:

• You cannot consume beverages or foods containing grapefruit for at least 2 weeks before the first dose of tesetaxel until 2 weeks after the last dose of tesetaxel.
• You also will not be allowed to receive any other anticancer treatments while receiving tesetaxel.
• It is important that you provide complete and accurate information about your medical history and any drugs you are taking or have taken in the past. False, misleading, or incomplete information could have a serious effect on your health.

This is an investigational study. Tesetaxel is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 27 patients will take part in this study. All will be enrolled at M. D. Anderson.

• Advanced Melanoma
• Cancer

Inclusion Criteria:

1. At least 18 years of age.
2. Histologically confirmed diagnosis of melanoma.
3. Progressive disease that is not surgically resectable, or metastatic Stage IV disease.
4. Measurable disease.
5. Serum LDH </= 1.1 times the upper limit of normal (x ULN).
6. Eastern Cooperative Oncology Group performance status 0 or 1.
7. Treatment with 1 prior regimen (including cytotoxic chemotherapy, immunotherapy, radiation therapy, or cytokine, biologic, or vaccine therapy) as first-line treatment for metastatic disease. (Administration of interleukin-2 or interferon as adjuvant therapy is allowed and is not to be considered in determining the 1 prior treatment regimen administered as first-line treatment for metastatic disease.)
8. Adequate bone marrow, hepatic, and renal function, as evidenced by: a) Absolute neutrophil count (ANC) >/= 1500/mm^3; b) Platelet count >/= 100,000/mm^3; c) Hemoglobin >/= 9 g/dL without need for hematopoietic growth factor or transfusion support; d) Aspartate aminotransferase (AST) </= 2.5 x ULN or, in the presence of liver metastasis, </= 5 x ULN; e) Alanine aminotransferase (ALT) </= 2.5 x ULN or, in the presence of liver metastasis, </= 5 x ULN f. Total bilirubin </= 1.5 x ULN;
9. (Continued # 8) g) Alkaline phosphatase </= 2.5 x ULN or, in the presence of liver metastasis, </= 5 x ULN or, in the presence of bone metastasis, </= 10 x ULN; h) Serum creatinine </= 1.5 x ULN; i) Serum albumin >/= 3.0 g/dL; j) Prothrombin time (PT) </= 1.5 x ULN (or international normalized ratio [INR] </=1.3); k) Partial thromboplastin time (PTT) </= 1.5 x ULN.
10. At least 3 weeks and recovery from effects of prior surgery or other therapy with an approved or investigational agent.
11. Ability to swallow an oral solid-dosage form of medication.
12. A negative serum pregnancy test within 7 days prior to the first dose of study medication in women of childbearing potential (that is, all women except for those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization).
13. Agreement to use a highly effective form of contraception (ie, one that has a failure rate of < 1%) throughout the treatment phase of the study in women of childbearing potential (that is, all women excluding those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization) and sexually active men
14. Written informed consent and authorization to use and disclose health information.
15. Ability to comprehend and to comply with the requirements of the study.

Exclusion Criteria:

1. At least 18 years of age.
2. Histologically confirmed diagnosis of melanoma.
3. Progressive disease that is not surgically resectable, or metastatic Stage IV disease.
4. Measurable disease.
5. Serum LDH </= 1.1 times the upper limit of normal (x ULN).
6. Eastern Cooperative Oncology Group performance status 0 or 1.
7. Treatment with 1 prior regimen (including cytotoxic chemotherapy, immunotherapy, radiation therapy, or cytokine, biologic, or vaccine therapy) as first-line treatment for metastatic disease. (Administration of interleukin-2 or interferon as adjuvant therapy is allowed and is not to be considered in determining the 1 prior treatment regimen administered as first-line treatment for metastatic disease.)
8. Adequate bone marrow, hepatic, and renal function, as evidenced by: a) Absolute neutrophil count (ANC) >/= 1500/mm^3; b) Platelet count >/= 100,000/mm^3; c) Hemoglobin >/= 9 g/dL without need for hematopoietic growth factor or transfusion support; d) Aspartate aminotransferase (AST) </= 2.5 x ULN or, in the presence of liver metastasis, </= 5 x ULN; e) Alanine aminotransferase (ALT) </= 2.5 x ULN or, in the presence of liver metastasis, </= 5 x ULN f. Total bilirubin </= 1.5 x ULN;
9. (Continued # 8) g) Alkaline phosphatase </= 2.5 x ULN or, in the presence of liver metastasis, </= 5 x ULN or, in the presence of bone metastasis, </= 10 x ULN; h) Serum creatinine </= 1.5 x ULN; i) Serum albumin >/= 3.0 g/dL; j) Prothrombin time (PT) </= 1.5 x ULN (or international normalized ratio [INR] </=1.3); k) Partial thromboplastin time (PTT) </= 1.5 x ULN.
10. At least 3 weeks and recovery from effects of prior surgery or other therapy with an approved or investigational agent.
11. Ability to swallow an oral solid-dosage form of medication.
12. A negative serum pregnancy test within 7 days prior to the first dose of study medication in women of childbearing potential (that is, all women except for those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization).
13. Agreement to use a highly effective form of contraception (ie, one that has a failure rate of < 1%) throughout the treatment phase of the study in women of childbearing potential (that is, all women excluding those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization) and sexually active men
14. Written informed consent and authorization to use and disclose health information.
15. Ability to comprehend and to comply with the requirements of the study.