Pazopanib Hydrochloride in Treating Patients With Advanced or Refractory Solid Tumors

NCT01552356 | Active Not Recruiting Phase 1

• 8 other identifiers: NCI-2012-00690MAYO-MC1112CDR0000727235MC11129076P30CA015083U01CA069912UM1CA186686
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and the best dose of pazopanib hydrochloride in treating patients with solid tumors that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or does not respond to treatment (refractory). Pazopanib hydrochloride may prevent the growth of new blood vessels that tumors need to grow. Studying samples of blood in the laboratory from patients receiving pazopanib hydrochloride may help doctors learn more about the effects of the body on the drug. It may also help doctors understand how well patients respond to treatment.

Conditions

Solid Neoplasm

Outcome Measures

Primary Outcomes (10)

• Biologically optimal dose (BOD) defined as the dose level and diet in combination that induces no toxicity requiring dose modification per protocol and achieves a satisfactory pazopanib trough concentration (Cmin greater than 30 ug/mL)

  At 14 days

• Adverse events profile, as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  The number and severity of all adverse events (overall, by dose-level and diet, and by tumor group) will be tabulated and summarized.

  Up to 3 months

• Incidence of grade 3+ adverse events, as assessed by the NCI CTCAE version 4.0

  The number and severity of grade 3+ adverse events will be tabulated and summarized.

  Up to 3 months

• Toxicity profile, as assessed by the NCI CTCAE version 4.0

  Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Up to 3 months

• Response profile, assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST)

  Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population The summary will be overall and by tumor group, and particularly by cohorts (first 34 patients vs. expansion cohort where a possibly refined definition of disease progression will be used).

  Up to 3 months

• Time until any treatment-related toxicity, as assessed by the NCI CTCAE version 4.0

  Up to 3 months

• Time until treatment-related grade 3+ toxicity, as assessed by the NCI CTCAE version 4.0

  Up to 3 months

• Time until hematologic nadirs (ANC, platelets, hemoglobin) , as assessed by the NCI CTCAE version 4.0

  Up to 3 months

• Time to progression according to RECIST version 1.1

  Up to 3 months

• Time to treatment failure

  From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months

Secondary Outcomes (3)

• Pazopanib hydrochloride levels attained in response to standard dosing

  At baseline, at 24 hours after pazopanib hydrochloride and day 14 of course 1, and at 14 days of dosage change

• Steady state pazopanib hydrochloride trough levels

  24 hours after initiation of 800 mg daily fasting

• Trough pazopanib hydrochloride levels

  After 14 days of pazopanib hydrochloride administration

Study Arms (1)

Treatment (pazopanib hydrochloride)

EXPERIMENTAL

Patients receive pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course length can be extended to 56 days at the discretion of the treating physician after 12 courses (1 year) of treatment on study.

Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pazopanib hydrochloride)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW 786034B, GW-786034B, GW786034B, Pazopater, Votrient

Treatment (pazopanib hydrochloride)

Pharmacological Study OTHER

Correlative studies

Treatment (pazopanib hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Histologic proof of cancer which is now not amenable to alternative curative or clearly superior standard treatment options
• Measurable disease
• Hemoglobin (Hgb) \>= 8.0 g/dL
• Absolute neutrophil count (ANC) \>= 1,500/uL
• Platelet (PLT) = 100,000/uL
• Activated partial thromboplastin time (APTT) \< 1.2 times upper limit of normal (ULN); (Note: use of warfarin is prohibited; low molecular weight heparin is allowed, so long as these criteria are met)
• International normalized ratio (INR) \< 1.2 times ULN; (Note: use of warfarin is prohibited; low molecular weight heparin is allowed, so long as these criteria are met)
• Direct bilirubin =\< 1.5 X upper limit of normal (ULN) (subjects with Gilbert's syndrome and elevations of indirect bilirubin only are eligible)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 X ULN
• Creatinine =\< 1.5 times ULN OR measured creatinine clearance of \>= 60 mL/min 1.73 m\^2
• Urine protein/creatinine ratio \< 1 or 24-hour urine \< 1 gram
• \< Grade 2 hypo/hyperkalemia
• \< Grade 3 hypo/hypercalcemia
• \< Grade 3 hypo/hyperphosphatemia
• \< Grade 3 hypo/hypermagnesemia

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Corrected QT interval (QTc) \>= 480 msec and/or receiving any concomitant medications that are associated with a risk of QTc prolongation and/or torsades de pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks
• Subjects with any of the following cardiovascular conditions within the past 6 months
• Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
• Admission for unstable angina
• Myocardial infarction
• Cardiac angioplasty or stenting
• Coronary artery bypass graft surgery
• Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
• Arterial thrombosis
• Symptomatic peripheral vascular disease
• Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
• Active cardiac arrhythmia (except sinus arrhythmia, atrial fibrillation, asymptomatic premature ventricular contractions \[PVCs\])
• Ejection fraction \< institutional lower limit of normal (LLN) and/or history of cardiomyopathy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

pazopanib

Study Officials

• Keith C Bible

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2012
• First Posted: March 13, 2012
• Study Start: March 19, 2012
• Primary Completion: December 31, 2015
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (2)