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

NCT01497392 | Completed Phase 1

• 2 other identifiers: I 175610NCI-2010-02034
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Plasma pharmacokinetic parameters of dovitinib lactate, gemcitabine hydrochloride, capecitabine and their metabolites

  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

  Up to 1 year

• Pancreas cancer cohort: survival, response rate and progression free survival

  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)

Study Arms (1)

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

EXPERIMENTAL

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.

Drug: dovitinib lactate; Drug: gemcitabine hydrochloride; Drug: capecitabine; Other: laboratory biomarker analysis; Other: enzyme-linked immunosorbent assay; Other: pharmacological study

Interventions

dovitinib lactate DRUG

Given PO

Also known as: CHIR-258, receptor tyrosine kinase inhibitor TKI258, RTK inhibitor TKI258, TKI258

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

capecitabine DRUG

Given PO

Also known as: CAPE, Ro 09-1978/000, Xeloda

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

enzyme-linked immunosorbent assay OTHER

Correlative studies

Also known as: ELISA

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (dovitinib lactate, gemcitabine, and capecitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Novartis: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Gemcitabine; Capecitabine; Enzyme-Linked Immunosorbent Assay

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Immunoenzyme Techniques; Immunoassay; Immunologic Techniques; Investigative Techniques; Immunosorbent Techniques; Immunohistochemistry; Molecular Probe Techniques

Study Officials

• Renuka Iyer

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: December 22, 2011
• Study Start: March 29, 2012
• Primary Completion: August 31, 2015
• Study Completion: February 7, 2017
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

US (1)