Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Amino Acids

Pemetrexed

Crizotinib

Folic Acid Antagonists

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Pemetrexed: 200 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Starting dose for Pemetrexed: 200 mg/m2 by vein on Day 1 of a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Pemetrexed: 400 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Crizotinib - Groups A, B, C: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Expansion Groups Starting Dose: MTD from Phase 1.

Crizotinib (Xalkori)

Starting Dose for Pazopanib - Groups A, C, D: 200 mg by mouth daily in a 21 day cycle.

Expansion Groups Starting Dose: MTD from Phase 1.

Pazopanib

Starting dose for Pemetrexed - Groups B + C: 200 mg/m2 by vein on Day 1 of a 21 day cycle.

Expansion Groups Starting Dose: MTD from Phase 1.

Starting dose for Pemetrexed Group D: 400 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Expansion Group Starting Dose: MTD from Phase 1.

Sarina Piha-Paul, MD

The goal of this clinical research study is to find the highest tolerable dose of the combination of Xalkori (crizotinib) either with Votrient (pazopanib) or Alimta (pemetrexed) or of the combination of 3 study drugs that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied.

Crizotinib is designed to block a protein called ALK, which is involved in cancer cell growth and survival.

Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.

Pemetrexed is designed to block proteins that may cause tumors to grow.

This is an investigational study. Crizotinib is FDA approved and commercially available for the treatment of locally advanced or metastatic non-small cell lung cancer. Pazopanib is FDA approved and commercially available for treatment of advanced renal cell carcinoma. Pemetrexed is FDA approved and commercially available for the treatment of non-small cell lung cancer.

The combination of crizotinib with pazopanib, crizotinib with pemetrexed, pazopanib with pemetrexed, and giving all 3 drugs together to patients with advanced cancer is investigational.

Up to 364 patients will take part in this study. All will be enrolled at MD Anderson.

Study groups:

Dose escalation:

If you are found to be eligible to take part in this study, your doctor will decide if you will receive one of the following drug combinations:

* If you are in Group A, you will receive crizotinib and pazopanib.
* If you are in Group B, you will receive crizotinib and pemetrexed.
* If you are in Group C, you will receive pazopanib and pemetrexed.
* If you are in Group D, you will receive crizotinib, pazopanib, and pemetrexed.

Once it is decided which combination you will receive, you will be assigned to a dose level based on when you join the study.

Up to 8 dose levels of crizotinib with pazopanib will be tested. Up to 6 dose levels of crizotinib with pemetrexed will be tested. Up to 6 dose levels of pazopanib with pemetrexed will be tested. Up to 8 dose levels of pazopanib with pemetrexed and crizotinib will be tested. Up to 6 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 combination is found.

Dose expansion:

Once the highest tolerable dose of each study drug combination is found, up to 14 more participants may be enrolled to further study the safety of each combination of drugs at that dose.

Study Drug Administration:

Each study cycle is 21 days. Drugs should be taken and/or administered simultaneously. On days of pharmacokinetic testing (if you agree) you should take the drugs at least 1 hour before or 2 hours after a meal.

If you are taking crizotinib, you will take it by mouth at the same time every day consistently either with or without food. It should be swallowed whole with a glass of water. You will take the drug every other day, 1 or 2 times a day. You will be told how often to take this drug.

If you are taking pazopanib, you will take it by mouth at the same time every day with a glass of water. You should take it at least 1 hour before or 2 hours after a meal.

If you receive pemetrexed:

* You will receive it by vein on Day 1 of each cycle over about 10 minutes.
* The day before your first dose of pemetrexed, you will start taking folic acid to help lower the risk of side effects. Although the study drug is designed to prevent the body from making folic acid that could help cancer grow and spread, some folic acid is needed to prevent side effects in non-cancerous tissue. You will take folic acid by mouth 1 time every day until at least 30 days after you received the last dose of pemetrexed.
* The day before your first dose of pemetrexed, you will receive a vitamin B12 injection. You will receive an injection of Vitamin B12 about every 9 weeks after that. Vitamin B12 is given to help reduce the risks of side effects.
* You will take dexamethasone by mouth 2 times a day on the day before, the day of, and the day after you receive pemetrexed.

Study Visits:

At every study visit, you will be asked about any other drugs or herbal supplements you are taking and about any side effects you may have.

During Cycles 1 and 2, you will have weekly blood (about 1 tablespoon) collected for routine tests.

During Week 1 of Cycles 2 and beyond:

* Your medical history will be recorded, including any cancer symptoms.
* You will have a physical exam, including measurement of your weight and vital signs.
* Your performance status will be recorded.
* Blood (about 1 tablespoon) and urine will be collected for routine tests.
* If your doctor thinks it is needed, you will have an ECG to check your heart function.

Every 6 weeks, or earlier if needed, blood (about 1 tablespoon) will be drawn for tumor marker testing.

After about 6 weeks and then every 2-3 cycles after that, you will have a CT scan, x-ray, MRI scan, and/or PET scan to check the status of the disease. It may be done more often if your study doctor thinks it is needed.

If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test every 2 cycles or at any time the study doctor thinks it is needed.

Length of Study Participation:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs 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 once you have completed the end-of-dosing and/or follow-up visits.

End-of-Dosing Visit:

Within 30 days after your last dose of study drugs, you will have an end-of-study visit. If you are having side effects at the time of this visit, you may have follow-up for a longer period of time. At this visit, the following tests or procedures may be performed:

* Your medical history will be recorded, including any cancer symptoms.
* You will be asked if you have had any side effects.
* You will have a physical exam, including measurement of your weight and vital signs.
* Your performance status will be recorded.
* Blood (about 1 tablespoon) and urine will be collected for routine tests.
* Blood (about 1 tablespoon) will be drawn for tumor marker testing.
* If the doctor thinks it is needed, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check the status of the disease.
* If your doctor thinks it is needed, you will have an ECG to check your heart function.

Pazopanib or Pemetrexed and Crizotinib in Advanced Cancer

A Two Steps Phase I Trial of Pazopanib or Pemetrexed in Combination With Crizotinib Followed by the Triplet, Crizotinib Plus Pazopanib Plus Pemetrexed in Patients With Advanced Malignancies

If not more than 33% of participants in cohort develop dose limiting toxicity (DLT), this cohort considered MTD. MTD defined by DLTs that occur in first cycle (4 weeks). DLT defined as: Clinically grade 3 or 4 non-hematologic toxicity. Grade 4 hematologic toxicity lasting 3 weeks or longer. Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens. Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE v4.0 attributable to therapy.

M.D. Anderson Cancer Center

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antibodies

Antibodies, Monoclonal

Carboplatin

Bevacizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

The chemotherapy will be Carboplatin (AUC 6) and Pemetrexed (500 mg/m2) every 3 weeks for 4 cycles.

Then maintenance Pemetrexed (500 mg/m2 every 3 weeks) will be administered until disease progression or excessive toxicity.

If patients are randomized into one of the arms with a biologic therapy, patients will take the chemotherapy prescribed above, but will also receive the biologic therapy during the same time period.

Carboplatin AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles. Pemetrexed 500 mg/m2 by vein on day 1 of each 21 day cycle. Bevacizumab 15 mg/kg by vein on day 1 of each 21 day cycle.

Carboplatin AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles. Pemetrexed 500 mg/m2 by vein on day 1 of each 21 day cycle.

Carboplatin AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles. Pemetrexed 500 mg/m2 by vein on day 1 of each 21 day cycle.

Cixutumumab 20 mg/kg by vein on day 1 of each 21 day cycle.

AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles.

500 mg/m2 by vein on day 1 of each 21 day cycle.

15 mg/kg by vein on day 1 of each 21 day cycle.

20 mg/kg by vein on day 1 of each 21 day cycle.

Cixutumumab

George Simon, MD

The goal of this clinical research study is to learn if knowing biomarker status can help researchers find better treatment combinations for patients with advanced NSCLC.

Researchers want to use biomarker status to decide what drug (bevacizumab, or cixutumumab) to give in combination with carboplatin and pemetrexed. The safety of these drug combinations will also be studied.

The Study Drugs:

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Pemetrexed is designed to block enzymes in the body that play a part in tumor growth.

Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells.

Cixutumumab is a monoclonal antibody, which means that it attaches to specific targets on cancer cells. These targets are called IGF-1R and help the cancer cells grow and divide. Cixutumumab is designed to block these receptors on tumor cells that may cause tumors to grow.

Study Groups and Drug Administration (Combination Therapy):

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 3 groups. You will have an equal chance of being assigned to each group. Each cycle is 21 days (+/- 5 days).

* If you are in Group 1, you will receive carboplatin and pemetrexed on Day 1 of each cycle. Carboplatin will be given by vein over 10 minutes. Pemetrexed will be given by vein over 30 minutes.
* If you are in Group 2, you will receive bevacizumab, carboplatin, and pemetrexed on Day 1 of each cycle. Bevacizumab will be given by vein over about 90 minutes for the first dose, about 60 minutes for the second dose, and about 30 minutes for all other doses. Carboplatin will be given by vein over 10 minutes. Pemetrexed will be given by vein over 30 minutes.
* If you are in Group 3, you will receive cixutumumab, carboplatin, and pemetrexed on Day 1 of each cycle. Cixutumumab is given by vein over 60 minutes. Carboplatin will be given by vein over 10 minutes. Pemetrexed will be given by vein over 30 minutes.

Study Visits During Combination Therapy:

If you are in Group 3, before you begin receiving study drugs, you will have a hearing test.

On Day 1 (+/- 5 days) of Cycles 1, 2, and 4:

* You will have a physical exam, including measurement of your weight and vital signs.
* You will be asked about any drugs you may be taking and any side effects you may be having.
* Your performance status will be recorded.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* If you are in Group 2, urine will be collected for routine tests.

On Days 8 and 15 of Cycle 1:

°If you are in Group 3, blood (about 1 teaspoon) will be drawn for routine tests.

On Day 1 of Cycle 3:

* You will have a physical exam, including measurement of your weight and vital signs.
* You will be asked about any drugs you may be taking and any side effects you may be having.
* Your performance status will be recorded.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* You will have a CT scan and/or MRI scan of the chest (and abdomen if the doctor thinks it is needed) to check the status of the disease.
* You will have an MRI scan of the brain.
* You will have a chest x-ray to check the status of the disease.
* If you are in Group 2, urine will be collected for routine tests.

At any time your doctor thinks it may be needed, blood (about 1 teaspoon) will be drawn to check how well your blood clots.

Maintenance Therapy:

After you have completed 4 cycles of combination therapy, you may be eligible for maintenance therapy.

If you are in Group 1,you will receive pemetrexed by vein over 10 minutes on Day 1 (± 5 days) of every 21-day cycle.

If you are in Group 2, you will receive pemetrexed by vein over 10 minutes and bevacizumab over about 30 minutes on Day 1 (± 5 days) of every 21-day cycle.

If you are in Group 3, you will receive pemetrexed by vein over about 10 minutes and cixutumumab by vein over about 60 minutes on Day 1 (± 5 days) of every 21-day cycle.

Study Visits During Maintenance Therapy:

On Day 1 of each cycle:

* You will have a physical exam, including measurement of your weight and vital signs.
* You will be asked about any drugs you may be taking and any side effects you may be having.
* Your performance status will be recorded.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* You will have a CT scan and/or MRI scan of the chest (and abdomen if the doctor thinks it is needed) to check the status of the disease.
* You will have an MRI scan of the brain.
* You will have a chest x-ray to check the status of the disease.
* If you are in Group 2, urine will be collected for routine tests.

Length of Study:

You may continue taking the study drug(s) 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.

Your participation on the study will be over once you have completed the end-of-dosing visit and follow-up.

End-of-Dosing Visit:

When you go off study for any reason, you will have an end-of-dosing visit. The following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a complete physical exam, including measurement of your weight and vital signs.
* You will be asked about any drugs you may be taking and any side effects you may be having.
* Your performance status will be recorded.
* Blood (about 3 teaspoons) and urine will be collected for routine tests.
* You will have a CT scan and/or MRI of the chest (and abdomen if the doctor thinks it is needed) to check the status of the disease.
* You will have an MRI scan of the brain.
* You will have a chest x-ray.
* You will have an ECG.
* If you are in Group 3, you will have a hearing test.

Follow-Up:

You will have follow-up every 4 weeks after you are no longer taking the study drugs. You will be contacted at a clinic visit or by phone. You will be called every 3 months for up to 3 years and asked about any cancer treatments you may be receiving. This phone call should take about 10 minutes.

This is an investigational study. Carboplatin and pemetrexed are FDA approved and commercially available for the treatment of certain types of NSCLC. Bevacizumab is FDA approved and commercially available for treatment of certain types of colon or rectal cancer, NSCLC, and renal cell carcinoma. Cixutumumab is not FDA approved or commercially available. At this time, cixutumumab is only being used in research.

Up to 225 patients will take part in this study. All will be enrolled at MD Anderson.

BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer

BATTLE-FL: A Biomarker-Integrated Study in Patients With Advanced Non-Small Cell Lung Cancer Treated in the Front-Line (FL) Setting

It is defined as from treatment start to the time of progression or death, whichever occurred first, or to the time of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Tumor response was assessed every two cycles of completed therapy. Responses will be based on a comparison to the pretreatment tumor evaluation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Eli Lilly and Company

Genentech, Inc.

Patients who were evaluable for toxicity and grades 1-3 adverse events.

Four 21-day cycles of combination AUC 6 of carboplatin and 500 mg/m2 of pemetrexed; maintenance pemetrexed and pemetrexed every 21 days until disease progression

Carboplatin + Pemetrexed x 4 Cycles Followed by Maintenance Pe

Four 21-day cycles of combination AUC 6 of carboplatin, 500 mg/m2 of pemetrexed, and 15 mg/kg of bevacizumab; maintenance pemetrexed and bevacizumab every 21 days until disease progression

Carboplatin + Pemetrexed + Bevacizumab Followed by Maintenance

Four 21-day cycles of combination AUC 6 of carboplatin, 500 mg/m2 of pemetrexed, and 250 mg/m2 of cetuximab (400mg/m2 on Cycle 1, Day 1 only); maintenance pemetrexed and cetuximab every 21 days until disease progression

Carboplatin + Pemetrexed + Cetuximab Followed by Maintenance P

Four 21-day cycles of combination AUC 6 of carboplatin, 500 mg/m2 of pemetrexed, and 20 mg/kg of cixutumumab; maintenance pemetrexed and cixutumumab every 21 days until disease progression

Carboplatin + Pemetrexed + Cixutumumab Followed by Maintenance

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. George Simon, Thoracic/Head & Neck Med Onc

Progression Free Survival

No change/Stable Disease

Partial Remission

Progressive Disease

Overall Response Rate

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Gemcitabine

Antimetabolites

Pemetrexed 500 mg/m\^2 intravenous (IV) and Gemcitabine 1500 mg/m\^2 IV on Day 1.

1500 mg/m\^2 IV Over 30 Minutes on Day 1, Immediately After Infusion of Pemetrexed.

Nizar M. Tannir, MD

Primary Objective:

* To determine the clinical activity of Pemetrexed + Gemcitabine in non-clear cell renal cell cancer (RCC). Clinical activity will take into account response rate and progression free survival (PFS).

Secondary Objectives:

* To determine the toxicity of Pemetrexed + Gemcitabine in non-clear cell RCC.
* To estimate the survival rate of patients with non-clear cell RCC treated with this combination.

Pemetrexed is a chemotherapy drug that is used to treat cancer. It is given intravenously (by IV--through a vein in your arm). It interferes with cell reproduction.

Gemcitabine is a cancer-fighting (chemotherapy) drug that is given by IV. It interferes with the growth of cells and is used to treat cancer.

Dexamethasone has many different medical uses. It is used to treat cancer, nausea, vomiting, inflammation, allergic reactions, and many other conditions. In this study, it is being given to prevent rashes.

Folic acid and Vitamin B12 are vitamins given to prevent serious side effects which can occur with chemotherapy. These side effects include diarrhea and a decrease in you red blood cells, white blood cells, and your blood platelets.

You will be required to take folic acid and vitamin B12. You will take folic acid, by mouth, daily beginning about 1 week before the first dose of Pemetrexed. You will continue to take it daily until 3 weeks after the last dose of chemotherapy. Vitamin B12 will be given as an injection into your muscle about 1 to 2 weeks before your first dose of Pemetrexed. You will have injections of vitamin B12 about every 9 weeks until 3 weeks after your last dose of chemotherapy.

During treatment, you will be given Pemetrexed by IV for 10 minutes, followed by Gemcitabine by IV for 30 minutes on Day 1 of each 2-week study "cycle."

You will take Dexamethasone tablets by mouth, 2 times a day on the day before, the day of, and the day after each dose of Pemetrexed. Dexamethasone is taken to prevent rashes. If you could not or did not take Dexamethasone the day before and/or the day of Pemetrexed, you may be given Dexamethasone by IV over 20 minutes, 30 minutes before the infusion of Pemetrexed.

You will have blood samples (about 4 teaspoons) drawn every week to test your bone marrow. You will have blood samples (about 1 teaspoon) drawn every 2 weeks to make sure that your kidneys and liver are working well. You will have a physical exam every 2 weeks before you receive chemotherapy. You will also be asked about any medications you have been taking since your last visit.

Once every 8 weeks or after 4 cycles of treatment, you will have the tumor(s) measured using standard of care imaging which may include a CT scan, MRI, or a bone scan.

You will be treated for as long as you are benefiting from the therapy. You will continue to receive treatment unless your tumor grows, intolerable side effects occur, or you develop another illness that prevents you from continuing with the therapy. You may also be taken off study if you fail to comply with the study requirements. If you are taken off study for any reason, you and your doctor will discuss other treatment options at that time.

If you are taken off study, you will be asked to have the same scans as before, a physical exam, and routine blood (about 4 teaspoons). You will be contacted every 3 months after being off study, to get an update on your health status.

This is an investigational study. Pemetrexed and Gemcitabine are FDA approved and commercially available. About 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Pemetrexed Plus Gemcitabine in Renal Cell Cancer

Phase II Trial of Pemetrexed Plus Gemcitabine in Patients With Advanced Non-Clear Cell Renal Cell Cancer

Number of participants with complete or partial response. Response Evaluation Criteria in Solid Tumors (RECIST) of Complete Response: disappearance all target lesions; Partial Response: \>30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease: \>20% increase sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1 or \> new lesions; Stable Disease: Insufficient shrinkage for partial response, or insufficient increase for progressive disease, reference smallest sum LD since treatment started.

Of the 16 participants enrolled, one participant started the study but withdrew prior to receiving any treatment and is therefore excluded from adverse event reporting.

Pemetrexed + Gemcitabine

Age Continuous

Quality Assurance Specialist

One participant did not meet the required 16 week data end point and was excluded from the response evaluation and analysis.

Overall Response

Heart and Blood Diseases

Pleural Effusion, Malignant

Pleural Effusion

Pericardial Effusion

Alimta 500 mg/m\^2 by vein Once Over 10 Minutes Every 3 Weeks.

500 mg/m\^2 by vein Once Over 10 Minutes Every 3 Weeks

Alimta

Ralph Zinner, MD

The goal of this clinical research study is to learn how effective the drug pemetrexed (ALIMTA®) is in treating advanced NSCLC in patients with poor performance status (PS) (inability to perform every day activities without difficulty).

Objectives:

Primary Objectives:

* PS = 2 cohort: Response
* PS = 3 cohort: Descriptive

Secondary Objectives:

* Tolerability of single agent pemetrexed (Alimta®) in PS = 3 NSCLC patients
* Improved symptoms (both cohorts)
* Molecular Correlative studies (both cohorts)
* Overall survival
* Time to progression

Pemetrexed is designed to block enzymes in the body that are important for tumor growth. Pemetrexed is commercially approved for the treatment of NSCLC but not for poor performance status patients.

If participants are found to be eligible to take part in this study, they will receive pemetrexed once every 3 weeks through a needle in their vein over about 10 minutes. Every 3 weeks is considered 1 treatment cycle. Once the treatment has started, they will return to the clinic before every treatment cycle. At these visits, they will have a physical exam, a performance status evaluation, and routine blood (about 3-4 teaspoons) and urine tests. They will have a chest x-ray and will be asked to complete a questionnaire about how you are feeling. they will also have a CT or MRI scan after Cycle 1 and every odd cycle from then on.

They are required to take folic acid by mouth every day for 5 days before the first dose of pemetrexed and continuing until 3 weeks after your last dose of pemetrexed. They will also receive an injection of vitamin B12 into your muscle before first dose of pemetrexed. The vitamin B12 injection will be repeated every 9 weeks until 3 weeks after their last dose of pemetrexed.

They will also to take a few low-dose steroid (dexamethasone) tablets twice a day before treatment, the day of treatment, and the day after each treatment. These will be taken to decrease the risk of rash and nausea caused by pemetrexed.

They may continue treatment with pemetrexed until your tumor grows or an unacceptable side effect occurs. They will be evaluated for symptoms 1-2 times per week while you are receiving treatment and then 2 weeks after stopping study treatment until 6 months after stopping treatment.

When they stop treatment on this study, they will have a physical exam, routine blood (3-4 teaspoons) and urine tests, and a chest x-ray. The study doctor may ask them to visit University of Texas MD Anderson Cancer Center or be contacted by phone for follow-up on how they are doing.

This is an investigational study. The FDA has approved pemetrexed for the treatment of advanced NSCLC after earlier treatment with chemotherapy, and for the treatment for malignant mesothelioma in combination with cisplatin. About 70 patients will take part in this study. All will be enrolled at MD Anderson.

Single Agent Alimta in Poor Performance Status in Non-small Cell Lung Cancer

Single Agent Alimta in Poor Performance Status in Patients With Non-Small Cell Lung Cancer (NSCLC)

Complete Response (CR): Complete disappearance of all measurable \& non-measurable disease; No new lesions; No disease related symptoms; Normalization of markers \& other abnormal lab values.

Partial Response (PR): Applies only to those with at least one measurable lesion. \>/= 30% decrease under baseline of sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions assessed using same techniques as baseline.

Progression: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using same techniques as baseline. Unequivocal progression of non-measurable disease in opinion of treating physician.

Evaluated for symptoms 1-2 times per week while receiving treatment then 2 weeks after stopping study treatment (expected 4 cycles).

Alimta 500 mg/m\^2 by vein once over 10 minutes every 3 weeks.

Gender

Ralph Zinner, MD/Thoracic & Head and Neck Medicine

Of 58 eligible participants, only 54 treated were available for response and five (5) experienced an early death, five (5) were later deemed inevaluable, and two had an indeterminate response.

Objective Response Rate (OR) Where OR=CR+PR: Number of Participants With Responses of Complete Response (CR) and Partial Response (PR)

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Mesothelial

Pleural Neoplasms

Malignant Mesothelioma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Cisplatin

Dexamethasone acetate

BB 1101

Imatinib Mesylate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Cisplatin 60 mg/m\^2 by vein, Over 2 Hours. Imatinib 300 mg PO Daily. Pemetrexed 500 mg/m\^2 by vein, Over 40 Minutes. Dexamethasone 20 mg by vein given prior to Pemetrexed therapy and 4 mg given orally on Day 2 of each cycle.

Starting Dose: 60 mg/m\^2 by vein, Over 2 Hours

Starting Dose: 500 mg/m\^2 by vein, Over 40 Minutes

20 mg by vein given prior to Pemetrexed therapy and 4 mg given orally on Day 2 of each cycle.

Anne S. Tsao, MD

Primary Objective:

* To determine the maximum tolerated dose of the combination of cisplatin, imatinib mesylate, and pemetrexed in metastatic malignant mesothelioma.

Secondary Objectives:

* To explore the biologic effects of cisplatin, imatinib mesylate, and pemetrexed on tumor tissue by:
* histologic analysis of biopsy tissue
* by non-invasive assessments of tumor vascularity performed before, during and after treatment
* electron microscopy analysis of endothelial cell architecture after patient treatment with imatinib mesylate
* To explore the effects of cisplatin, imatinib mesylate, and pemetrexed on surrogate markers in serum.
* To assess the rate of response to therapy.
* To determine the doses of the combination regimen of cisplatin, imatinib mesylate, and pemetrexed that enables de-phosphorylation of platelet derived growth factor receptor (PDGF-R) on malignant mesothelioma tumor cells.
* To determine the pharmacokinetic interaction between agents in this combination regimen.

Cisplatin is used to treat different cancers, including testicular, germ cell, head and neck, bladder, and lung cancer. This drug has an atom-containing platinum, which is designed to poison cancer cells, causing them to die.

Pemetrexed is designed to block enzymes in the body that play a part in tumor growth.

Imatinib mesylate is a drug that blocks certain proteins that play a part in the development of cancer. Imatinib mesylate has also been shown to increase the effect of chemotherapy in tumor cells.

Before you can start treatment on this study, 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 your complete medical history recorded and a physical exam, including measurement of your vital signs (temperature, pulse, breathing rate, and blood pressure) and weight. An ECOG performance status evaluation (a test looking at your ability to perform day-to-day activities) will be done. Blood will be drawn (about 3 to 4 teaspoons) through a needle in your vein for routine tests. You will be asked about any medications you are taking. Women who are able to have children must have a negative blood pregnancy test. Also, your tumor will be evaluated by magnetic resonance imaging (MRI) or computerized tomography (CT) scans before the start of this study.

If you are found to be eligible to take part in this study, you will begin taking imatinib mesylate. Depending on when you begin treatment on this study, you may be asked to take 3, 4, or 6 tablets of imatinib mesylate by mouth once a day. Your doctor will also ask you to take folic acid tablets (or a multivitamin with folic acid) during the week before you receive your first infusion of pemetrexed and then every day while you are on this study. You will also be given an injection of vitamin B12. The vitamin B12 shot will be repeated every 9 weeks during treatment on this study. Folic acid and vitamin B12 will help to decrease the risk of severe side effects from pemetrexed.

After 1 week of imatinib mesylate and folic acid, you will receive cisplatin and pemetrexed by IV infusion. Cisplatin (given over 2 hours) and pemetrexed (given over 40 minutes) will be given on the first day of each treatment cycle for a total of 6 cycles. Each cycle is 28 days long.

Dexamethasone will also be given by vein before you receive pemetrexed. Dexamethasone will help to decrease the risk of rash and nausea that may be caused by pemetrexed. Your doctor will also ask you to take dexamethasone tablets by mouth twice a day (12 hours apart) only on Day 2 of each cycle.

Every 4 weeks, you will have a physical exam, including measurement of your vital signs and weight. You will also have a performance status evaluation. Blood will be drawn (about 3 to 4 teaspoons) through a needle in your vein for routine tests. Also, at every 8 weeks, your tumor will be measured by a CT or an MRI scan.

After you complete 6 treatment cycles of cisplatin and pemetrexed, you will continue to take imatinib mesylate tablets every day up to 1 month after the 6 treatment cycles. If you develop any intolerable side effects or if your disease gets worse, your treatment on this study may be delayed; the dose of the study drugs decreased until your side effects are gone; or you may be taken completely off this study. Your doctor will talk with you about any changes in your dosing schedule or in the doses of your medication after you been evaluated in the clinic.

After you have completed all of your treatment, you will have what is called an end-of-study visit. At this visit, you will have a physical exam, including measurement of your vital signs and weight. You will have an ECOG performance status evaluation. You will have blood drawn (about 3 to 4 teaspoons) through a needed in your vein for routine tests. You will also have your tumor measured by CT or an MRI scan.

This is an investigational study. Both cisplatin and pemetrexed have been approved by the FDA for the treatment of malignant mesothelioma. The FDA has approved imatinib mesylate for the treatment of leukemia and certain sarcomas; however, it has been authorized by the FDA for use in research only in the treatment of malignant mesothelioma. Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.

Cisplatin, Pemetrexed, and Imatinib Mesylate in Malignant Mesothelioma

Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or Metastatic Malignant Mesothelioma

MTD defined as the highest dose level in which 6 patients have been treated with less than or equal to 2 instances of dose limiting toxicity (DLT). DLT characterized by the National Cancer Institute (NCI) Common Toxicity Criteria. DLT defined as (1) febrile neutropenia (fever \> grade 2 with grade 4 neutropenia and requiring IV antibiotics); (2) grade 4 neutropenia (ANC \< 500/mL) for more than seven days duration; (3) grade 4 thrombocytopenia; (4) grade 3 or 4 non-hematologic toxicity (except alopecia).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pazopanib or Pemetrexed and Crizotinib in Advanced Cancer	NCT01548144	Advanced Cancer...	Crizotinib (Xal... Pazopanib Pemetrexed	18 Years -	M.D. Anderson Cancer Center
BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer	NCT01263782	Lung Cancer	Carboplatin Pemetrexed Bevacizumab Cixutumumab	18 Years -	M.D. Anderson Cancer Center
Pazopanib or Pemetrexed and Crizotinib in Advanced Cancer	NCT01548144	Advanced Cancer...	Crizotinib (Xal... Pazopanib Pemetrexed	18 Years -	M.D. Anderson Cancer Center
Pemetrexed Plus Gemcitabine in Renal Cell Cancer	NCT00491075	Renal Cell Carc...	Pemetrexed Gemcitabine	-	M.D. Anderson Cancer Center
Single Agent Alimta in Poor Performance Status in Non-small Cell Lung Cancer	NCT00508144	Lung Cancer	Alimta	18 Years -	M.D. Anderson Cancer Center
Single Agent Alimta in Poor Performance Status in Non-small Cell Lung Cancer	NCT00508144	Lung Cancer	Alimta	18 Years -	M.D. Anderson Cancer Center
Cisplatin, Pemetrexed, and Imatinib Mesylate in Malignant Mesothelioma	NCT00402766	Mesothelioma	Cisplatin Imatinib Mesyla... Pemetrexed Dexamethasone	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for ly231514

Every month we try and update this database with for ly231514 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ly231514

Every month we try and update this database with for ly231514 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ly231514 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.