Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Adenocarcinoma

Recurrence

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Gemcitabine

Albumin-Bound Paclitaxel

Tyrosine Kinase Inhibitors

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive dovitinib lactate PO QD 5 days per week, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

dovitinib lactate

gemcitabine hydrochloride

paclitaxel albumin-stabilized nanoparticle formulation

pharmacological study

laboratory biomarker analysis

Wen Wee Ma

This phase I trial studies the highest and safest doses of dovitinib lactate, paclitaxel albumin-stabilized nanoparticle formulation, and gemcitabine hydrochloride when given together. Dovitinib lactate disrupts the activity of fibroblast growth factor receptors and reduces cancer growth and spread. Gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation are anti-cancer drugs for treating many cancer types.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and recommended phase II dose of dovitinib (dovitinib lactate) when administered concurrently with gemcitabine (gemcitabine hydrochloride) and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in patients with advanced solid malignancies.

II. To characterize the safety profile of dovitinib, gemcitabine and nab-paclitaxel combination in patients with advanced solid malignancies.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetic profile of dovitinib, nab-paclitaxel, gemcitabine and their metabolites when administered concurrently in patients with advanced solid malignancies.

II. To determine the preliminary efficacy of the study combination in patients with advanced solid tumors and pancreas adenocarcinoma.

III. To explore serum and tumor biomarkers predictive of efficacy to the study combination.

OUTLINE: This is a dose-escalation study of dovitinib lactate.

Patients receive dovitinib lactate orally (PO) once daily (QD) 5 days per week, paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Dovitinib Lactate, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Solid Tumors or Pancreatic Cancer

A Phase Ib Study of Dovitinib in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Solid Tumors and Pancreatic Cancer

Characterized by type, frequency, timing, seriousness and relationship to study treatment. All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment. Demographic data and baseline disease characteristics will be displayed, and summary statistics will be used to describe patient population.

Pharmacokinetic parameters will be summarized for each cohort of patients. Comparison of PK parameters among the dose levels will be performed using non-parametric statistical methods for K-independent samples. Drug-drug interaction will be examined comparing PK parameters using nonparametric statistical methods.

Overall survival will be estimated using Kaplan-Meier method.

Differences in biomarkers between responders and non-responders will be explored with frequencies and summary statistics. Tests for differences in continuously measured biomarkers will be done with standard two-sample testing procedures. Categorical biomarkers will be tested with Fisher's exact test.

National Cancer Institute (NCI)

Novartis

Roswell Park Cancer Institute

Biliary Tract Cancer

Capecitabine

Patients receive dovitinib lactate PO on days 1-5, 8-12, and 15-19, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and capecitabine PO twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

capecitabine

enzyme-linked immunosorbent assay

Renuka Iyer

This phase I trial is studying the side effects and best dose of dovitinib lactate when given together with gemcitabine hydrochloride and capecitabine in treating patients with advanced or metastatic solid tumors or advanced pancreatic cancer. Dovitinib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving dovitinib lactate together with combination chemotherapy may kill more tumor cells

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and recommended phase II dose of dovitinib (dovitinib lactate) when administered concurrently with gemcitabine (gemcitabine hydrochloride) and capecitabine in patients with advanced solid malignancies.

II. To characterize the safety profile of dovitinib, gemcitabine and capecitabine combination in patients with advanced solid malignancies.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetic profile of dovitinib, capecitabine, gemcitabine and their metabolites when administered concurrently in patients with advanced solid malignancies.

II. To determine the preliminary efficacy of the study combination in patients with advanced adenocarcinoma of the pancreas or biliary tract.

III. To explore serum and tumor biomarkers predictive of efficacy to the study combination.

OUTLINE: This is a dose-escalation study of dovitinib lactate.

Patients receive dovitinib lactate orally (PO) on days 1-5, 8-12, and 15-19, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, and capecitabine PO twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 3 months for 1 year.

Dovitinib Lactate, Gemcitabine Hydrochloride, and Capecitabine in Treating Patients With Advanced or Metastatic Solid Tumors, Pancreatic Cancer and Biliary Cancers

Phase I Study of Dovitinib (TKI258) in Combination With Gemcitabine and Capecitabine in Advanced Solid Tumors, Pancreatic Cancer and Biliary Cancers

All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.

Differences in biomarkers between responders and non-responders will be explored with frequencies and summary statistics. Biomarkers will be tested with Fisher's exact test. Pharmacokinetic parameters will be summarized for each cohort of patients. Comparison of pharmacokinetic parameters among the dose levels will be performed using non-parametric statistical methods for K-independent samples. Drug-drug interaction will be examined comparing pharmacokinetic parameters using nonparametric statistical methods.

Tumor response will be defined according to the RECIST criteria version 1.1.

Tumor response will be defined according to the RECIST criteria version 1.1. Overall survival for patients enrolled to Part B will be estimated using Kaplan-Meier method.

Carcinoma

Neuroendocrine Tumors

Carcinoma, Islet Cell

Insulinoma

Gastrinoma

Glucagonoma

Somatostatinoma

Zollinger-Ellison Syndrome

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Adenoma

Adenoma, Islet Cell

Neoplasms, Glandular and Epithelial

Carcinoma, Neuroendocrine

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

Patients receive dovitinib lactate PO on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Emily Bergsland

This phase II trial studies how well dovitinib lactate works in treating patients with pancreatic neuroendocrine tumors. Dovitinib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of dovitinib (dovitinib lactate) in patients with progressive well-differentiated neuroendocrine tumors of the pancreas (PNETs) in reference to 6-month progression free survival (PFS) historical-controlled patients and in two cohorts defined by prior vascular endothelial growth factor (VEGF)-inhibitor therapy (Cohort 1 - no prior VEGF, Cohort 2 - prior VEGF).

SECONDARY OBJECTIVES:

I. To determine the safety of dovitinib in patients with progressive well-differentiated PNETs.

II. To evaluate time to treatment failure, time to progression, and overall survival.

III. To evaluate radiographic and biochemical response rates.

TERTIARY OBJECTIVES:

I. To assess the pharmacodynamic effect of dovitinib on plasma biomarkers by measuring concentrations of circulating growth factors and soluble receptors (e.g. basic fibroblast growth factor \[bFGF\], VEGF, placental growth factor \[PLGF\], soluble VEGF receptor 1 (sVEGFR1) and 2, collagen IV, fibroblast growth factor 23 \[FGF23\]).

II. Archival tissue collected from patients prior to registration will be banked to later analyze baseline expression of potential biomarkers (e.g., bFGF, FGFR).

OUTLINE:

Patients receive dovitinib lactate orally (PO) on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 6 months, every 3 months for 6 months, and then periodically for 2 years.

Dovitinib Lactate in Treating Patients With Pancreatic Neuroendocrine Tumors

Phase II Study of Dovitinib (TKI-258) in Progressive, Well-Differentiated Pancreatic Neuroendocrine Tumors With and Without Prior VEGF-Inhibitor Therapy

The relationship between these biomarkers and clinical outcome in this patient population will be explored. Statistical methods include: two-sample t-tests with adjustment for multiple comparisons of continuous biomarker variables between treatment groups, Wilcoxon and Kruskal-Wallis tests and chi-square tests for ordinal categorical variables between groups, regression methods to assess the prognostic factors on molecular targets, and Kaplan-Meier survival methods for time to disease progression or time to target resistance.

The relationship between these biomarkers and clinical outcome will be explored in this patient population.

Confidence intervals for the estimate of 6-month PFS will be calculated using the method of Duffy and Santner.

Kaplan-Meier methodology will be used to estimate the distribution of survival and provide point estimates at various time points.

Assessed using categorical data analysis.

Maximum severity of each adverse event (AE) will be summarized using summary statistics, graphical techniques, and categorical methods, thereafter summarized by patient cohort. AEs will be also reviewed and summarized in consideration of relationship to study treatment (i.e., attribution).

Academic and Community Cancer Research United

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Erlotinib Hydrochloride

Patients receive erlotinib hydrochloride PO QD. Starting on day 15, patients also receive dovitinib lactate PO QD on days 1-5 of each week. Treatment continues in the absence of disease progression or unacceptable toxicity.

Erlotinib hydrochloride

Dovitinib lactate

Heather Wakelee

This phase I trial studies the side effects and best dose of giving erlotinib and dovitinib together to treat patients with metastatic non-small cell lung cancer. Erlotinib blocks the epidermal growth factor receptor (EGFR) and has known activity in non-small cell lung cancer and dovitinib blocks the fibroblast growth factor receptor (FGFR) and other targets which may be important to treat lung cancer. The combination of both drugs may work better than either drug alone, but may also have increased side effects. This trial will look at the side effects of combining the drugs and look for how effective the combination may be.

PRIMARY OBJECTIVES:

I. To characterize the safety and tolerability of the combination of erlotinib (erlotinib hydrochloride) and dovitinib (dovitinib lactate), assessing for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

II. To determine the maximum tolerated dose (MTD) of the combination of erlotinib and dovitinib.

SECONDARY OBJECTIVES:

I. To evaluate overall response rate (ORR), progression free survival (PFS), and overall survival (OS) of patients receiving the combination of erlotinib and dovitinib, although this phase will allow for patients who received any number of prior treatments, including prior treatment with erlotinib.

II. To evaluate the potential impact of dovitinib on erlotinib pharmacokinetics (PK).

OUTLINE: This is a dose-escalation study.

Patients receive erlotinib hydrochloride orally (PO) once daily (QD). Starting on day 15, patients also receive dovitinib lactate PO QD on days 1-5 of each week. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 months.

Phase 1 Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer (NSCLC)

A Phase I Study of Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer

Dose limiting toxicity (DLT) is defined as a CTCAE v4.0 toxicity \>= grade 3 or 4 occurring after 3 weeks of treatment. If 2 of 6 patients experience a DLT, then the MTD will be defined as the dose tolerated by the cohort preceding the cohort experiencing the DLT.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dovitinib Lactate, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Solid Tumors or Pancreatic Cancer	NCT02048943	Duct Cell Adeno... Recurrent Pancr... Stage III Pancr... Stage IV Pancre... Unspecified Adu...	dovitinib lacta... gemcitabine hyd... paclitaxel albu... pharmacological... laboratory biom...	18 Years -	Roswell Park Cancer Institute
Dovitinib Lactate, Gemcitabine Hydrochloride, and Capecitabine in Treating Patients With Advanced or Metastatic Solid Tumors, Pancreatic Cancer and Biliary Cancers	NCT01497392	Adenocarcinoma ... Stage III Pancr... Stage IV Pancre... Unspecified Adu...	dovitinib lacta... gemcitabine hyd... capecitabine laboratory biom... enzyme-linked i... pharmacological...	18 Years -	Roswell Park Cancer Institute
Dovitinib Lactate, Gemcitabine Hydrochloride, and Capecitabine in Treating Patients With Advanced or Metastatic Solid Tumors, Pancreatic Cancer and Biliary Cancers	NCT01497392	Adenocarcinoma ... Stage III Pancr... Stage IV Pancre... Unspecified Adu...	dovitinib lacta... gemcitabine hyd... capecitabine laboratory biom... enzyme-linked i... pharmacological...	18 Years -	Roswell Park Cancer Institute
Dovitinib Lactate, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Solid Tumors or Pancreatic Cancer	NCT02048943	Duct Cell Adeno... Recurrent Pancr... Stage III Pancr... Stage IV Pancre... Unspecified Adu...	dovitinib lacta... gemcitabine hyd... paclitaxel albu... pharmacological... laboratory biom...	18 Years -	Roswell Park Cancer Institute
Dovitinib Lactate in Treating Patients With Pancreatic Neuroendocrine Tumors	NCT02108782	Gastrinoma Glucagonoma Insulinoma Pancreatic Poly... Recurrent Islet... Somatostatinoma	dovitinib lacta... pharmacological... laboratory biom...	18 Years -	Academic and Community Cancer Research United
Phase 1 Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer (NSCLC)	NCT01515969	Non-small Cell ... Non-small Cell ...	Erlotinib hydro... Dovitinib lacta...	18 Years -	Stanford University

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