Study of Pazopanib and Ixabepilone in Patients With Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01012362
First received: November 12, 2009
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Lung Cancer
Colon Cancer
Pancreatic Cancer
Head and Neck Cancer
Kidney Cancer
Sarcoma
Hepatocellular Cancer
Drug: Pazopanib
Drug: Ixabepilone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Study of Pazopanib and Ixabepilone in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • To determine the optimal tolerated regimen (OTR) of pazopanib and ixabepilone when used in combination by evaluation of toxicity and tolerability [ Time Frame: At first cycle (Week 3) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To obtain preliminary toxicity and tolerability of this drug regimen. [ Time Frame: Up to 30 days post treatment ] [ Designated as safety issue: Yes ]

Enrollment: 31
Study Start Date: December 2009
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib and Ixabepilone

Patient receives assigned dose level:

Dose Level 1 = 400 milligrams (mg) of pazopanib and ixabepilone 25 mg/m2. Dose Level 2 = 400 milligrams (mg) of pazopanib and ixabepilone 32 mg/m2. Dose Level 3 = 600 milligrams (mg) of pazopanib and ixabepilone 32 mg/m2. Dose Level 4 = 800 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.
Other Names:
  • Pazopanib hydrochloride
  • GW786034B
Drug: Ixabepilone
Escalating doses 25-32 mg/m2 by intravenous infusion on day 1 of each 21 day cycle
Other Name: IXEMPRA(TM)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01012362

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
GlaxoSmithKline
Investigators
Principal Investigator: Arkaduisz Z Dudek, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01012362     History of Changes
Other Study ID Numbers: 2009LS001, 0906M68402, NCI-2009-01444
Study First Received: November 12, 2009
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
Solid tumor malignancy
breast cancer
lung cancer
colon cancer
pancreatic cancer
head and neck cancer
kidney cancer
sarcoma
hepatocellular cancer

Additional relevant MeSH terms:
Breast Neoplasms
Colonic Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Head and Neck Neoplasms
Liver Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Sarcoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 21, 2014