Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Tubulin Modulators

Antineoplastic Agents, Alkylating

Alkylating Agents

Starting dose of TPI 287 90 mg/m\^2 IV on Days 1, 8, 15 + Temozolomide (Temodar) PO at 85 mg/m\^2 on Days 1-5.

Starting dose cycle 1, 90 mg/m2 by vein (IV) on Days 1, 8, 15 (+/- 1 day)

TPI 287

Starting dose cycle 1, 85 mg/m\^2 by mouth (PO) daily, Day 1 to 5.

Temodar (Temozolomide)

Rodabe N Amaria, MD

The goal of the Phase I portion of this study is to find the highest tolerable dose of TPI 287 that can be given in combination with Temodar (temozolomide) to patients with metastatic melanoma.

The goal of the Phase II portion of this study is to learn if TPI 287, given in combination with temozolomide, can control metastatic melanoma. The safety of this combination will also be studied. NOTE: Study stopped before progressing to Phase II portion.

Study Drugs:

TPI 287 is designed to block tumors from growing by preventing cancer cells from dividing.

Temozolomide is designed to kill cancer cells by causing breaks in the DNA (genetic material) of the cell.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 8 groups of 6 participants will be enrolled in the Phase I portion of the study, and up to 64 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of TPI 287 and temozolomide you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of TPI 287 and temozolomide. Each new group will receive a higher dose of TPI 287 and temozolomide than the group before it, if no intolerable side effects were seen. If any of these participants have a dose limiting toxicity, 6 additional participants will be added at the same dose. If a dose limiting toxicity occurs again, the dose level below this will be considered the maximum tolerated dose.

If any participant experiences a life threatening side effect, no additional participants will be enrolled into that dose level and no higher doses will be given. An additional 3 participants will be treated at the dose level below the one with life threatening toxicity. Once the maximum tolerated dose of the combination is found, Phase II of the study will open.

If you are enrolled in the Phase II portion, you will receive the drug combination at the highest dose that was tolerated in the Phase I portion

Central Venous Catheter (CVC):

You will have a CVC placed. A CVC is a sterile, flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

Study Drug Administration:

You will receive TPI 287 by vein over 1 hour (+/- 10 minutes) on Days 1, 8, and 15 (+/- 1 day) of each 28 day study cycle. Before you receive each dose of TPI 287, you will receive dexamethasone, Benadryl (diphenhydramine), and Pepcid (famotidine) by vein to help prevent allergic reaction. You will also receive drugs to prevent nausea and vomiting. Your vital signs will be measured before and 30 minutes following the end of the infusion of TPI 287. Your vitals will be measured more often, if needed.

You will take temozolomide tablets by mouth on Days 1-5 at bedtime. You should not eat for at least 1 hour before and 1 hour after taking temozolomide.

Study Visits:

Before each cycle, your performance status will be recorded and you will have a physical exam. You will also be asked about any symptoms you may be experiencing and any drugs you are taking.

On Days 1, 8, and 14 of each cycle:

-Blood (about 1 teaspoon) will be drawn for routine tests before you receive TPI 287.

On Day 22 of each cycle:

-Blood (about 1 teaspoon) will be drawn for routine tests.

Every 8 weeks, you will have a CT scan or MRI scan to check the status of the disease. If you have brain metastasis, you will have an MRI of the brain every 4 weeks. If you do not have brain metastasis, you will have MRI of the brain every 8 weeks.

Length of Study:

You will continue taking the study drugs for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Treatment Visit:

About 4 weeks after you stop taking TPI 287 in combination with Temozolomide, you have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* You will be asked about any complications or side effects you may be experiencing.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If your doctor thinks it is needed, you will have a CT scan or MRI scan to check the status of the disease.

This is an investigational study. TPI 287 is not FDA approved or commercially available. At this time, TPI 287 is being used in research only. Temozolomide is FDA approved and commercially available for primary brain cancer. The use of temozolomide in combination with TPI 287 is investigational.

Up to 106 patients will take part in this study. All patients will be enrolled at MD Anderson.

A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma

A Phase I/II Open-Label Study TPI 287 in Combination With Temozolomide in Patients With Metastatic Melanoma

MTD is highest dose level in which 6 patients treated with at most 1 experiencing dose limiting toxicity (DLT).

Maximum Tolerated Dose (MTD), measured by clinical and laboratory adverse events.

Response rate provided along with a 95% credible interval. Logistic regression models used to assess the association between progression-free survival at 6 months and covariates of interest. Additionally, Cox proportional hazards regression models will be fit to model the association between progression-free survival and the same covariates. Simon's minimax two-stage design used to evaluate the response rate.

Cortice Biosciences, Inc.

M.D. Anderson Cancer Center

Symptoms and General Pathology

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Amino Acids

Methionine

Dietary Methionine Restriction (Hominex®-2) Days 1-7 and 15-21 + Temodar® 150 mg/m\^2 orally Days 8-15

150 mg/m\^2 orally once a day for 7 consecutive days (days 8 through 15).

Methionine free diet during Days 1 - 7 and Days 15 - 21 by consuming only "shakes" containing Hominex-2®.

Hominex-2

Morris D. Groves, MD

Objectives:

1. To determine the safety, tolerability and efficacy of dietary methionine restriction for 7 days alternating with Temodar® (Temozolomide) given once a day for seven days and this repeated for up to one year in the treatment of patients with recurrent and/or progressive glioblastoma.
2. To determine the short- and long-term toxicity of dietary methionine restriction combined with Temodar® in glioblastoma patients.
3. To measure and correlate patients' tumor responses and progression-free survival with: serum methionine and peripheral blood lymphocyte methylation levels. In any patient undergoing surgery, to measure tumor alkylguanyl transferase (AGT) and methionine levels and compare to control specimens.

Methionine is an essential amino acid. Many solid tumors depend on the methionine that is taken in through the diet. The tumors need methionine to grow. A methionine free (or reduced) diet may help to shrink or slow the growth of some tumors. Temozolomide is a drug that is commonly used in the treatment of glioma. A methionine free (or reduced) diet may increase the effectiveness of temozolomide in the treatment of glioma.

Before treatment, you will have a complete physical exam and blood (around 2 tablespoons) will be collected for routine tests. You will have either a magnetic resonance imaging (MRI) scan or a computed tomography (CT) scan of the brain. Women who are able to have children must have a negative blood pregnancy test. You will then meet with a study dietician. The dietician will give you written instructions and make a food plan based on your needs. The instructions and food plan will help you maintain a methionine-free (or reduced) diet during the study.

During the study, all participants will receive standard chemotherapy with temozolomide by mouth once a day at bedtime for 7 days on Days 8 through 14 and 22 through 28, every 28 days, 4 weeks This 4-week period is called a cycle of chemotherapy. This 4 week cycle will be repeated as long as the disease does not get worse.

During treatment, you will be asked to maintain a methionine free diet during Days 1 - 7 and Days 15 - 21. During the periods of methionine free diet, you will consume only "shakes" containing Hominex-2®. The Hominex-2® shakes are nutritionally complete and easy to prepare. You will be given instructions on how to maintain this methionine-free diet.

All participants enrolled in the study will consume a methionine free diet for 1 week, alternating with temozolomide chemotherapy for 1 week. The participants will then be switched to a methionine "replete" diet for 1 week while taking chemotherapy. This diet and chemotherapy schedule will be continued for as long as the treatment is effective and tolerable. This replete diet contains methionine. The dietician will record what you eat to make sure you are eating the right amount of methionine during this period. This 4-week schedule will be repeated as long as you are on the study.

If you experience any intolerable side effects or the disease gets worse, you will be taken off the study and your doctor will discuss other treatment options with you.

During treatment, you will have blood (around 1 tablespoon) collected every 2 weeks for routine tests. Every 4 weeks for the first 16 weeks then every 8 weeks for the rest of the study, you will have check up visits. At these visits, you will have a complete physical exam and have blood collected (around 1 tablespoon) for routine tests. You will also have a dietary consultation. Every 8 weeks during the study, you will have either a MRI scan or a CT scan of the brain. If your doctor feels it is necessary, the tests may be done more often or you may have other tests as needed for your care.

This is an investigational study. Methionine restriction diet (Hominex®-2 Amino Acid-Modified Medical Food) has been approved by the FDA for nutrition support of children and adults with vitamin B6-nonresponsive homocystinuria. However, its use in this study is investigational. Temozolomide has been approved by the FDA for the treatment of brain tumors and is commercially available. The use of this combination is experimental. Forty-four participants will take part in this study.

Dietary Methionine Restriction Plus Temozolomide for Recurrent GBM

A Phase I Study of Dietary Methionine Restriction and Temodar® (Temozolomide) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme

Time to progression measured from the first day of treatment until progression is documented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma	NCT01067066	Melanoma	TPI 287 Temodar (Temozo...	15 Years -	M.D. Anderson Cancer Center
Dietary Methionine Restriction Plus Temozolomide for Recurrent GBM	NCT00508456	Glioblastoma Mu...	Temodar (Temozo... Hominex-2	-	M.D. Anderson Cancer Center
A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma	NCT01067066	Melanoma	TPI 287 Temodar (Temozo...	15 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for temodar (temozolomide)