Dovitinib Lactate, Gemcitabine Hydrochloride, And Capecitabine In Treating Patients With Advanced Or Metastatic Solid Tumors, Pancreatic Cancer And Biliary Cancers

Study Overview

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

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.

Adenocarcinoma of the Pancreas
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific

DRUG: dovitinib lactate
DRUG: gemcitabine hydrochloride
DRUG: capecitabine
OTHER: laboratory biomarker analysis
OTHER: enzyme-linked immunosorbent assay
OTHER: pharmacological study

I 175610
NCI-2010-02034 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-02-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-07-20
First Submitted that Met QC Criteria 2011-12-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-07-22
First Posted (ACTUAL) 2011-12-22	Results First Posted N/A	Last Verified 2022-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (dovitinib lactate, gemcitabine, and 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 unaccepta	DRUG: dovitinib lactate Given PO DRUG: gemcitabine hydrochloride Given IV DRUG: capecitabine Given PO OTHER: laboratory biomarker analysis Correlative studies OTHER: enzyme-linked immunosorbent assay Correlative studies OTHER: pharmacological study Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (dovitinib lactate, gemcitabine, and 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 unaccepta

DRUG: dovitinib lactate

Given PO

DRUG: gemcitabine hydrochloride

Given IV

DRUG: capecitabine

Given PO

OTHER: laboratory biomarker analysis

Correlative studies

OTHER: enzyme-linked immunosorbent assay

Correlative studies

OTHER: pharmacological study

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose (MTD) is defined as the highest dose level at which less than 33% of patients experience study treatment-related dose limiting toxicities (DLT)	All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.	First course, 21 days
Overall safety profile characterized by type, frequency, severity (according to National Cancer Institute [NCI] CTCAE version 4.0), 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.	Up to 30 days post-treatment

Secondary Outcome Measures	Measure Description	Time Frame
Plasma pharmacokinetic parameters of dovitinib lactate, gemcitabine hydrochloride, capecitabine and their metabolites	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.	Day 1 and 19 of course 1, day 8 of course 2 (Part A); day -14, day 19 of course 1,and day 8 of course 2 (Part B)
Solid tumor/dose-finding cohort: response rate, progression free survival	Tumor response will be defined according to the RECIST criteria version 1.1.	Up to 1 year
Pancreas cancer cohort: survival, response rate and progression free survival	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.	At 6 months
Pharmacodynamic effects of dovitinib lactate and Gem-Cap combination on vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptors (FGFR) dynamics in serum and tumor specimens		Day 1, 12, and 19 of course (Part A); days -14, -3, and days 12 and 19 of course 1 (Part B)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Part A: histologically or cytologically confirmed solid tumors that ale advanced or metastatic that the gemcitabine combination is considered standard therapy or a rational option
Part B: histologically or cytologically confirmed adenocarcinoma of the pancreas or the biliary tract (cholangiocarcinoma)that is advanced or metastatic
Part B: must have tumor lesions amenable to safe biopsy and willing to consent to tumor biopsies
Patients with at least one measurable site of disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 that have not been previously irradiated
Eastern Cooperative Oncology Group (ECOG) Performance Status =< 1
Life expectancy >= 3 months
Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
Platelets >= 100,000 cells/mm^3
Hemoglobin >= 9.0 g/dL
Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 1.5 x Upper Limit of Normal (ULN)
Bilirubin =< 1.5 x ULN
Serum creatinine =< 1.5 x ULN
International normalized ratio (INR) =< 1.5 (anticoagulation is allowed if target INR =< 1.5 on a stable dose of warfarin or on a stable dose of low-molecular-weight heparin (LMW) heparin for > 2 weeks at the first dose of study agent);if urinalysis shows proteinuria, 24 hour urine collection is to be performed and the 24 hour urine protein is to be < 2 grams to be eligible
Willing and able to take oral medication, comply with scheduled visits, treatment plan and laboratory tests
Ability to understand and willingness to sign a written informed consent, a signed informed consent must be obtained prior to any specific procedures

Part B: Patients with history of another malignancy within the last three years prior to study entry, with exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer)
Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosourea, mitomycin-C, targeted therapy and radiation) =< 4 weeks prior to starting study drug, or who have not recovered from side effects of such therapy
Patients who have received the last administration of nitrosourea or mitomycin-C =< 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
Patients who have received targeted therapy (e.g. sunitinib, sorafenib, pazopanib) =< 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
Patients who have had radiotherapy =< 4 weeks prior to starting study drug, or =< weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device =< 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
History or presence of serious uncontrolled ventricular arrhythmias or presence of serious uncontrolled atrial fibrillation
Clinically significant resting bradycardia
Known left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher)
Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
Uncontrolled hypertension defined by a systolic blood pressure (SBP) of >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication
Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month
Any active gastrointestinal (GI) impairment which, in the opinion of the investigator, would impair or alter the absorption of dovitinib (e.g. ulcerative colitis, or Crohn's disease)
Positive hemoccult test result within 14 days prior to the start of study treatment
Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
Patients who are currently receiving oral anticoagulation treatment with therapeutic doses of warfarin with goal INR >= 1.5; patients receiving anticoagulation by subcutaneous injection such as heparin, enoxaparain, fondaparinix that are not expected to interact with study medications will be eligible
History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance
Uncontrolled diarrhea >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
Pregnant or breast-feeding women
Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 3 days prior to starting study treatment
Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception; male not using at least at least one form of highly effective contraception will be excluded; highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study
Patients with known brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Novartis

Investigators

PRINCIPAL_INVESTIGATOR: Renuka Iyer, Roswell Park Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

Patients

Caregivers

Clinical Trial Record