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

NCT02048943 | Withdrawn Phase 1

• 3 other identifiers: I 242513NCI-2014-00119P30CA016056
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of dovitinib lactate, defined as the highest dose level at which < 33% of patients experience study treatment-related dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0

  28 days

• Incidence of adverse events graded by NCI CTCAE version 4.0

  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.

  Up to 4 weeks

Secondary Outcomes (7)

• Plasma pharmacokinetic (PK) parameters of dovitinib lactate

  Pre-dose, 0.5, 1-2,4-5, 6-8, 24 hours post-dose day 1 of course 2; pre-dose trough day 8 of course 2

• Plasma PK parameters of gemcitabine hydrochloride

  Prior to end of infusion, and 0.5, 1-2, and 4-6 hours post-end of infusion day 1 of course 2; prior to infusion of IV chemotherapy day 8 of course 2

• Plasma PK parameters of paclitaxel albumin-stabilized nanoparticle formulation

  Prior to end of infusion, and 0.5, 1-2, and 4-6 hours post-end of infusion day 1 of course 2; prior to infusion of IV chemotherapy day 8 of course 2

• Survival (expansion cohort)

  6 months

• Response rate, defined according to RECIST 1.1 (expansion cohort)

  Up to 4 weeks

Study Arms (1)

Treatment (dovitinib, gemcitabine, nab-paclitaxel)

EXPERIMENTAL

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.

Drug: dovitinib lactate; Drug: gemcitabine hydrochloride; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

dovitinib lactate DRUG

Given PO

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

Treatment (dovitinib, gemcitabine, nab-paclitaxel)

gemcitabine hydrochloride DRUG

Given IV

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

Treatment (dovitinib, gemcitabine, nab-paclitaxel)

paclitaxel albumin-stabilized nanoparticle formulation DRUG

Given IV

Also known as: ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel

Treatment (dovitinib, gemcitabine, nab-paclitaxel)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (dovitinib, gemcitabine, nab-paclitaxel)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (dovitinib, gemcitabine, nab-paclitaxel)

Eligibility Criteria

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

You may qualify if:

• Part A and Part B2: Histologically or cytologically confirmed solid tumors that are advanced or metastatic that gemcitabine and/or nab-paclitaxel containing treatment is considered a rational option
• Part Bl: Histologically or cytologically confirmed adenocarcinoma of the pancreas that is locally advanced or metastatic
• Part Bl: At least one malignant lesion not previously irradiated that can be safely biopsied, and patient is agreeable to undergo fresh tumor biopsy
• Patients with at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 that has 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 (SI units 1.5 x 10\^9/L)
• Platelets \>= 100,000 cells/mm\^3 (SI units 100 x 10\^9/L)
• Hemoglobin \>= 9 g/dL (SI units 90 g/L)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate 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 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 comply with scheduled visits, treatment plan and laboratory tests

You may not qualify if:

• 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 =\< 2 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 intrapelvic), 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
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• 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-dimensional (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) \>= 160 mmHg 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
• National Cancer Institute (NCI): collaborator
• 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; Taxes; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel

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; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Wen Wee Ma

  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: January 27, 2014
• First Posted: January 29, 2014
• Study Start: March 1, 2015
• Primary Completion: November 1, 2015
• Last Updated: January 9, 2015

Record last verified: 2015-01

Locations

US (1)