Study Of Pazopanib And Ixabepilone In Patients With Solid Tumors

Study Overview

Study of Pazopanib and Ixabepilone in Patients With Solid Tumors

This is a Phase I study; dose escalating the combination of pazopanib when taken daily and ixabepilone when administered on day 1 of a 3 week treatment course.

Treatment with ixabepilone will be given at an assigned dose as a 3 hour intravenous infusion on day 1 of a 21 day cycle. Treatment with pazopanib will be given at an assigned dose by mouth once a day, beginning on day 1 and continuing daily. Disease assessment will be done every 2 cycles (6 weeks) with treatment continuing until disease progression, unacceptable toxicity or patient refusal.

Breast Cancer
Lung Cancer
Colon Cancer
Pancreatic Cancer
Head and Neck Cancer
Kidney Cancer
Sarcoma
Hepatocellular Cancer

DRUG: Pazopanib
DRUG: Ixabepilone

2009LS001
0906M68402 (OTHER Identifier) (OTHER: Institutional Review Board, University of Minnesota)
NCI-2009-01444 (REGISTRY Identifier) (REGISTRY: National Cancer Institute website)

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 2009-11-12	Results First Submitted 2017-04-11	Last Update Submitted that met QC Criteria 2017-12-03
First Submitted that Met QC Criteria 2009-11-12	Results First Submitted that Met QC Criteria 2017-04-11	Last Update Posted (ACTUAL) 2017-12-28
First Posted (ACTUAL) 2009-11-13	Results First Posted 2017-06-26	Last Verified 2017-12

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:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Optimum Tolerated Dose Determination Patient receives assigned dose level: Dose Level 1 = 400 milligrams (mg) of pazopanib and ixabepilone 32 mg/m2. Dose Level 2 = 400 milligrams (mg) of pazopanib and ixabepilone 40 mg/m2. Dose Level 3 = 600 milligrams (mg) of pazopanib and ixabepilone 32 m	DRUG: Pazopanib Escalating doses 400-800 mg by mouth once daily beginning day 1 and continuing. DRUG: Ixabepilone Escalating doses 25-32 mg/m2 by intravenous infusion on day 1 of each 21 day cycle
EXPERIMENTAL: Optimum Tolerated Dose Confirmation Dose Level 3 = 600 milligrams (mg) of pazopanib and ixabepilone 32 mg/m2.	DRUG: Pazopanib Escalating doses 400-800 mg by mouth once daily beginning day 1 and continuing. DRUG: Ixabepilone Escalating doses 25-32 mg/m2 by intravenous infusion on day 1 of each 21 day cycle

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Optimum Tolerated Dose Determination

Patient receives assigned dose level: Dose Level 1 = 400 milligrams (mg) of pazopanib and ixabepilone 32 mg/m2. Dose Level 2 = 400 milligrams (mg) of pazopanib and ixabepilone 40 mg/m2. Dose Level 3 = 600 milligrams (mg) of pazopanib and ixabepilone 32 m

DRUG: Pazopanib

Escalating doses 400-800 mg by mouth once daily beginning day 1 and continuing.

DRUG: Ixabepilone

Escalating doses 25-32 mg/m2 by intravenous infusion on day 1 of each 21 day cycle

EXPERIMENTAL: Optimum Tolerated Dose Confirmation

Dose Level 3 = 600 milligrams (mg) of pazopanib and ixabepilone 32 mg/m2.

DRUG: Pazopanib

Escalating doses 400-800 mg by mouth once daily beginning day 1 and continuing.

DRUG: Ixabepilone

Escalating doses 25-32 mg/m2 by intravenous infusion on day 1 of each 21 day cycle

Primary Outcome Measures	Measure Description	Time Frame
The Optimal Tolerated Regimen of Pazopanib and Ixabepilone When Used in Combination	The optimal tolerated regimen is the regimen where ≤ 1 out of 6 patients experiences a dose limiting toxicity (DLT). DLT is defined as one of the following events occurring during cycle 1: grade 4 or greater treatment related hematologic toxicity for > 7 days during the first cycle (21 days) of therapy; grade 3 or greater treatment related clinical non-hematological toxicity (excluding ≥ grade 3 nausea, vomiting, or diarrhea without maximal medical intervention and/or prophylaxis) during the first cycle (21 days) of therapy; or a delay of cycle 2 treatment start by more than 2 weeks due to incomplete hematologic recovery (ANC > 1.5 x 109/L or platelets 100 x 109/L) or unresolved treatment related grade 3 or greater non-hematologic toxicity.	Week 3 of each dose level
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)	A DLT was defined as one of the following events occurring during cycle 1: (1) grade 4 or greater treatment-related hematologic toxicity for >7 days; (2) grade 3 or greater treatment-related clinical non-hematologic toxicity (excluding >/= grade 3 nausea, vomiting, or diarrhea without maximal medical intervention and/or prophylaxis); or (3) delay of starting cycle 2 treatment by >2 weeks due to incomplete hematologic recovery (absolute neutrophil count > 1.5 X 10^9/L or platelets >100 X 10^9/L) or unresolved treatment-related grade 3 or greater non-hematologic toxicity. Adverse events were classified according to Common Terminology Criteria for Adverse Events V 3.0 (CTCAE).	Week 3 of each dose

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events	Includes all treatment-related adverse events experienced during and subsequent to Cycle 1.	Up to 30 days post treatment

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:

Diagnosis of advanced non-hematologic solid tumor malignancy, including, but not limited to breast, lung, colon, pancreatic, head and neck, kidney or sarcoma that has failed or become intolerant to standard therapy and is no longer likely to respond to such therapy Effective with the August 2011 version of the protocol, enrollment is limited to squamous cell carcinoma of the head and neck (refer to section 1.4 for rationale). Note: Patients with a primary diagnosis of hepatocellular carcinoma will be eligible for enrollment into dose level 1 or 2 only, provided they met all other inclusion/exclusion criteria - the maximum tolerated dose (MTD) for pazopanib monotherapy in patients with hepatocellular cancer was found to be 600 mg daily.
Measureable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed; however prior use of either pazopanib or ixabepilone alone or in combination is not allowed.
At least 14 days must have elapsed since 1) previous systemic therapy (28 days for bevacizumab) before the 1st dose of study drug, 2) last dose of radiation therapy or surgery (28 days for major surgery).
Patient must have recovered from the acute toxic effects of previous anti-cancer treatment prior to study enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Adequate organ function within 14 days of enrollment defined as:

Absolute neutrophil count (ANC) >1.5 x 10^9/L
Hemoglobin > or = 9 g/dL
Platelets > or = 100 x 10^9/L
Prothrombin time or international normalized ratio, and partial thromboplastin time (PTT) < or = 1.2 x upper limit of normal (ULN)
Total bilirubin < or = ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or = 2.5 x ULN
Serum creatinine < or = 1.5 mg/dL
Urine protein to Creatinine Ratio < 1
Total serum calcium < 12.0 mg/dL
Men and women with child-bearing potential must adhere to protocol criteria to prevent conception during study

Women who are pregnant or nursing.
Prior radiation to > =or = 30% of major bone marrow containing areas (pelvis, lumbar spine)
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
Clinically significant gastrointestinal abnormalities that may increase the risk of GI bleeding or may affect absorption of investigational product
History of another malignancy - must be at least 3 years disease-free
Presence of uncontrolled infection
Prolongation of corrected QT interval (QTc) > 480 msecs
History of any one or more of the following cardiovascular conditions within the past 6 months:

Cardiac angioplasty or stenting
Myocardial infarction
Unstable angina
Coronary artery bypass graft surgery
Symptomatic peripheral vascular disease
Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
Poorly controlled hypertension
History of cerebrovascular accident,pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
Prior major surgery or trauma within 28 days prior to 1st dose of study drug
Evidence of active bleeding or bleeding diathesis
Known endobronchial lesions or involvement of large pulmonary vessels by tumor
Hemoptysis with 6 weeks of 1st dose of study drug
Neuropathy Grade 1

Collaborators and Investigators

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

GlaxoSmithKline

Investigators

PRINCIPAL_INVESTIGATOR: Arkaduisz Z Dudek, MD, Masonic Cancer Center, University of Minnesota

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

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Resources

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Clinical Trial Record