Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Sorafenib

Antimetabolites

Protein Kinase Inhibitors

Enzyme Inhibitors

Treatment with Capecitabine and Sorafenib

During Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily). For Days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A) combined with sorafenib (400 mg twice daily); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows:

Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.

Capecitabine and Sorafenib

During Cycle 1, patients will receive capecitabine alone for the first 7 days Cohort B will receive 1000 mg/m2 of capecitabine twice daily for the first 7 days of Cycle 1). For Days 8-14 of Cycle 1, patients will receive capecitabine (1000 mg/m2 twice daily for Cohort B) combined with sorafenib (400 mg twice daily for both cohorts); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort B will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 1000 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.

Jeffrey Infante, M.D.

This is a phase I, randomized, safety and pharmacokinetic (PK) study of sorafenib given in combination with capecitabine. The study will enroll two simultaneous cohorts; patients will be randomly assigned to either Cohort A or Cohort B. A third cohort (C) may be added to the protocol at a later date.

During Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily, and Cohort B will receive 1000 mg/m2 of capecitabine twice daily for the first 7 days of Cycle 1). For days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A; 1000 mg/m2 twice daily for Cohort B) combined with sorafenib (400 mg twice daily for both cohorts); on days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily for both cohorts). Beginning with day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.

Cohort B will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 1000 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle. After 6 patients each are enrolled into Cohort A and Cohort B, one of these two cohorts will enroll an additional 6-12 patients in an expansion phase.

Study of the Pharmacokinetics/Safety of Sorafenib + Capecitabine in Advanced Solid Tumors

A Phase I Pharmacokinetic and Safety Study of Sorafenib + Capecitabine in Advanced Solid Tumors

Bayer

SCRI Development Innovations, LLC

Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Syndrome

Leukemia

Melanoma

Preleukemia

Myelodysplastic Syndromes

Leukemia, Lymphoid

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Bone Marrow Diseases

Precancerous Conditions

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Neuroendocrine Tumor

Neuroepithelioma

The SCRI Oncology Research Consortium will collect written consent from patients allowing the use of their tumor tissue sample(s) for testing/analysis at a future date.

If a patient consents to allowing the use of their tumor tissue sample(s) for testing/analysis at a future date, their name and information will be stored electronically in a registry that will be managed by SCRI. SCRI may then use the information contained in this registry (such as disease indication, demographic information, etc.) at any time in the future to select tissue samples on which to perform testing/analyses.

Tissue Registry Study

Howard Burris, M.D.

Sarah Cannon Research Institute (SCRI) is committed to improvement and excellence in clinical research and correlative science. To this end, the SCRI Oncology Research Consortium will collect written consent from patients allowing the use of their tumor tissue sample(s) for testing/analysis at a future date. Future testing may include assays for newly identified markers of potential prognostic and/or therapeutic value. These markers may be specific to an individual cancer type, or they may be present more generally in cancer and/or other conditions.

Sarah Cannon Research Institute (SCRI) is committed to improvement and excellence in clinical research and correlative science. To this end, the SCRI Oncology Research Consortium will collect written consent from patients allowing the use of their tumor tissue sample(s) for testing/analysis at a future date. Future testing may include assays for newly identified markers of potential prognostic and/or therapeutic value. These markers may be specific to an individual cancer type, or they may be present more generally in cancer and/or other conditions.

This study will consist of a registry of patients who have agreed to allow their tissue sample(s) (even those taken prior to their participation in an SCRI-sponsored trial) to be used by the SCRI Oncology Research Consortium at some point in the future for testing and analysis of expression analysis and/or analysis of tumor markers. The registry will be contained in an electronic database, and will be sorted by disease indication. (Note: Patients will not be asked to return at a future date and have tissue samples collected; rather, SCRI will have the authorization to obtain pre-existing samples).

Potential retention of tissue blocks for future study.

SCRI Tissue Testing Registry

Breast Neoplasms

Breast Diseases

Amino Acids

Lapatinib

Panobinostat

Tyrosine Kinase Inhibitors

Histone Deacetylase Inhibitors

Tyrosine

LBH589, Capecitabine and Lapatinib (Breast Cancer Patients)

LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.

LBH589

Capecitabine will be administered orally twice daily for 14 days out of every 21 days.

Lapatinib, 1000 mg PO daily will be added to this combination.

Howard A Burris, III, M.D.

This single center Phase I dose escalation trial will evaluate the safety, tolerability and efficacy of LBH589 when combined with capecitabine and lapatinib in three parts. Part 1 will determine the maximum tolerated doses (MTD) of LBH589 when combined with capecitabine. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 2 will evaluate the safety of the MTD of LBH589 determined in Part 1 when paired with lapatinib 1000 mg by mouth (PO) daily. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 3 will evaluate the tolerability and effectiveness of the triplet combination, LBH589, capecitabine and lapatinib in breast cancer patients.

LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.

The second portion of this study will assess QTc prolongation with the LBH589 and lapatinib combination. A subset of 6 patients will be treated with the LBH589 one dose below the MTD determined during Part I. If tolerated, 6 additional patients will receive LBH589 at the MTD established in Part I with lapatinib (capecitabine will not be administered in this subset of patients).

If there are no clinically significant findings in the LBH589 and lapatinib subset, the study will advance to a third portion which combines the three drugs LBH589, capecitabine, and lapatinib.

The triple combination will initially administer lapatinib 1000 mg orally daily with LBH589 and capecitabine at one dose level below the established MTD. If tolerated, LBH589 and capecitabine doses will be escalated to the MTD.

Toxicity assessments will be ongoing and disease assessments will be repeated every 2 treatment cycles. If all dose level combinations are explored, a total of 45-55 patients will be required to accommodate for the additional patients enrolled in the QTc subset and to establish the recommended phase II dose of the combination regimen.

LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients

A Phase I Study of LBH589 in Combination With Capecitabine ± Lapatinib

Novartis

MTD, LBH589 with Capecitabine

LBH589: LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.

Capecitabine: Capecitabine will be administered orally twice daily for 14 days out of every 21 days.

LBH589 With Capecitabine

LBH589 and Lapatinib

LBH589: LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.

Lapatinib: Lapatinib, 1000 mg PO daily will be added to this combination.

LBH589 and Lapatinib

LBH589, Capecitabine and Lapatinib (Breast Cancer Patients)

LBH589: LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.

Capecitabine: Capecitabine will be administered orally twice daily for 14 days out of every 21 days.

Lapatinib: Lapatinib, 1000 mg PO daily will be added to this combination.

LBH589, Capecitabine and Lapatinib

Total

Age, Continuous

Female

Male

Gender

United States

Region of Enrollment

John D Hainsworth, MD

MTD Determination only for part I patients (per protocol)

To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil

To Evaluate the Antitumor Activity of LBH589 in Combination With Capecitabine in Patients With Refractory and Advanced Tumors

To Evaluate the Tolerability and Preliminary Efficacy of Established Doses of LBH589 and Capecitabine With Lapatinib in a Limited Number of Patients With HER2+ Breast Cancer

Overall Study

Anti-Infective Agents

Epothilone B

Everolimus

Epothilones

Sirolimus

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

RAD001 will be taken orally starting at a dose of 30 mg every week for the first cohort of patients, one hour prior to administration of patupilone. Patupilone will then be administered as an infusion, starting at 5 mg/m2 for the first cohort of patients. The dosage and scheduling of RAD001 and patupilone during each 21-day cycle will vary according to cohort assignment

Patupilone

RAD001

Mark Stein, MD

This is an unblinded, dose escalation study of patupilone in combination with RAD001 in subjects with advanced cancer to find the maximum tolerated dose of each drug. The purpose of this study is to see what doses of RAD001 and patupilone are safe to use when the two drugs are used at the same time. Other goals in this study are to learn about the effect of RAD 001 and patupilone on tumor growth; to find out what amount of RAD001 is present in the blood when it is combined with patupilone; to learn about proteins in the blood that may predict or show an effect of RAD001 or patupilone and to learn if any changes are seen in the tumor with the type of test called a PET scan.Subjects will be assigned to a dosing group. The dose of patupilone and RAD001 a subject gets depends on when they enter onto this study. The initial subjects in the study will take the lowest doses of RAD001 and patupilone. At least 3 subjects will be treated in each dosing group starting with the smallest dose. If there are few or easy to handle side effects, the next group of at least 3 people to enter in the study will get the next higher dose. This continues until the highest dose of the study drug is found that does not cause serious or hard to treat side effects. Both the subjects and the study doctor will know which dose is assigned. In this study, RAD001 will be given as tablets to take with water. RAD001 will be taken for either 7, 14, or 21 days of each 21 day cycle depending on which dosing group is assigned. If taking RAD 001 and patupilone on the same day, then RAD 001 will be taken with water however prior to receiving patupilone.Patupilone will be given by an intravenous injection (through a vein) for 20 minutes on Days 1 or day 6 of the 21-day cycle. The patupilone dose will be based on height and weight. Blood tests (approximately 1-3 teaspoons) will be done every week. Every six weeks a CT scan or MRI will be done to assess the tumor size. Subjects will continue to receive RAD001 and patupilone as long as the tumor is stable or shrinking, and not having too many side effects from treatment.

Primary Endpoint To identify the maximum tolerated doses (MTD) of the combination of patupilone and RAD001

Secondary Endpoints To assess the toxicity of patupilone and RAD001 To determine if concentrations of RAD001 are elevated in the presence of patupilone To evaluate tumor response using standard imaging modalities (CT scan, x-ray, bone scan) To develop pharmacodynamic markers that may predict or indicate response to mTOR inhibition or patupilone treatment.

Phase I Study of Patupilone and RAD001

Phase I Study of Patupilone and RAD001 in Patients With Refractory Solid Tumor Malignancy

Novartis Pharmaceuticals

National Cancer Institute (NCI)

University of Medicine and Dentistry of New Jersey

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Pharmacokinetics/Safety of Sorafenib + Capecitabine in Advanced Solid Tumors	NCT00613145	Refractory Mali...	Capecitabine an... Capecitabine an...	18 Years -	SCRI Development Innovations, LLC
SCRI Tissue Testing Registry	NCT00965861	Melanoma Myelodysplastic... Multiple Myelom... Lymphoma	Tissue Registry...	18 Years -	SCRI Development Innovations, LLC
LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients	NCT00632489	Breast Cancer	LBH589 Capecitabine Lapatinib	18 Years -	SCRI Development Innovations, LLC
LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients	NCT00632489	Breast Cancer	LBH589 Capecitabine Lapatinib	18 Years -	SCRI Development Innovations, LLC
LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients	NCT00632489	Breast Cancer	LBH589 Capecitabine Lapatinib	18 Years -	SCRI Development Innovations, LLC
Phase I Study of Patupilone and RAD001	NCT00496600	Refractory Mali...	Patupilone RAD001	18 Years -	Rutgers, The State University of New Jersey

Spots Global Cancer Trial Database for refractory malignancy