Study of Pazopanib and Ixabepilone in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT01012362
• Recruitment Status: Terminated
• First Posted: November 13, 2009
• Results First Posted: June 26, 2017
• Last Update Posted: December 28, 2017
• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Cancer; Lung Cancer; Colon Cancer; Pancreatic Cancer; Head and Neck Cancer; Kidney Cancer; Sarcoma; Hepatocellular Cancer	Drug: Pazopanib; Drug: Ixabepilone	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of Pazopanib and Ixabepilone in Patients With Solid Tumors
• Study Start Date: December 2009
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: February 2013

Arms and Interventions

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 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)
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.; 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)

Outcome Measures

Primary Outcome Measures :

1. The Optimal Tolerated Regimen of Pazopanib and Ixabepilone When Used in Combination [ Time Frame: Week 3 of each dose level ]
   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.
2. Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) [ Time Frame: Week 3 of each dose ]
   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).

Secondary Outcome Measures :

1. Number of Participants With Treatment-Related Adverse Events [ Time Frame: Up to 30 days post treatment ]
   Includes all treatment-related adverse events experienced during and subsequent to Cycle 1.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT01012362
• Other Study ID Numbers: 2009LS001; 0906M68402 ( Other Identifier: Institutional Review Board, University of Minnesota ); NCI-2009-01444 ( Registry Identifier: National Cancer Institute website )
• First Posted: November 13, 2009
• Results First Posted: June 26, 2017
• Last Update Posted: December 28, 2017
• Last Verified: December 2017

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:

Pancreatic Neoplasms; Sarcoma; Head and Neck Neoplasms; Colonic Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Liver Neoplasms; Carcinoma, Hepatocellular; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial