Study of Pazopanib and Ixabepilone in Patients With Solid Tumors

NCT01012362 | Terminated Phase 1 Results DMC

• 3 other identifiers: 2009LS0010906M68402NCI-2009-01444
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Solid tumor malignancy; breast cancer; lung cancer; colon cancer; pancreatic cancer; head and neck cancer; kidney cancer; sarcoma; hepatocellular cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events

  Up to 30 days post treatment

Study Arms (2)

Optimum Tolerated Dose Determination

EXPERIMENTAL

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; Drug: Ixabepilone

Optimum Tolerated Dose Confirmation

EXPERIMENTAL

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

Drug: Pazopanib; Drug: Ixabepilone

Interventions

Pazopanib DRUG

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

Also known as: Pazopanib hydrochloride, GW786034B

Optimum Tolerated Dose Confirmation; Optimum Tolerated Dose Determination

Ixabepilone DRUG

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

Also known as: IXEMPRA(TM)

Optimum Tolerated Dose Confirmation; Optimum Tolerated Dose Determination

Eligibility Criteria

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Head and Neck Neoplasms; Kidney Neoplasms; Sarcoma; Liver Neoplasms

Interventions

pazopanib; ixabepilone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Liver Diseases

Results Point of Contact

• Title: Dr. Arkadiusz Dudek
• Organization: Masonic Cancer Center, University of Minnesota

Arkadiusz.Z.Dudek@HealthPartners.com

651-254-3321

Study Officials

• Arkaduisz Z Dudek, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2009
• First Posted: November 13, 2009
• Study Start: December 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: December 28, 2017
• Results First Posted: June 26, 2017

Record last verified: 2017-12

Locations

US (1)