Pazopanib Hydrochloride Followed by Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma

NCT01446809 | Completed Results

• 3 other identifiers: 7487NCI-2011-02488P30CA015704
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized pilot clinical trial studies pazopanib hydrochloride followed by chemotherapy and surgery in treating patients with soft tissue sarcoma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes that are needed for cell growth and may also stop the growth of soft tissue sarcoma by blocking blood flow to the tumor. Giving pazopanib hydrochloride and chemotherapy before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed.

Conditions

Stage IIA Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (5)

• Change in Maximum SUV of Tumors Measured by FDG-PET Pre- and Post Receipt of Pazopanib Versus Placebo

  Change in maximum SUV (standardized uptake value) of tumors measured by FDG-PET. Comparison conducted using a two-sided Wilcoxon rank sum test.

  From baseline to 15 days

• Change in Maximum SUV of Tumors Measured by FDG-PET Post Receipt of 2 Courses of Preoperative Chemotherapy

  Change in maximum SUV of tumors measured by FDG-PET. Comparison conducted using a two-sided Wilcoxon rank sum test.

  From baseline to 8 weeks

• Tumor Response by RECIST Criteria

  RECIST measurements will be performed on serial MRIs to evaluate the correlation with FDG-PET. The longest diameter (LD) of the target lesions will be measured and reported as the baseline LD. The baseline LD will be used as reference to further characterize the objective tumor response of the measurable dimension of the disease.Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression (PD), a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  At 15 days

• Tumor Response by RECIST Criteria

  RECIST measurements will be performed on serial MRIs to evaluate the correlation with FDG-PET. The longest diameter (LD) of the target lesions will be measured and reported as the baseline LD. The baseline LD will be used as reference to further characterize the objective tumor response of the measurable dimension of the disease.Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression (PD), a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  At 8 weeks

• Pharmacokinetic Profile of Pazopanib

  Trough plasma pazopanib concentration measured during the 14 day run-in period on days 10 through 14.

  Up to 14 days

Secondary Outcomes (4)

• Change in Levels of VEGF and Soluble VEGFR2 Assessed by ELISA on Plasma and Tumor Extracts

  At baseline and after 14 days

• Overall Survival

  Up to 3 years

• Number of Participants With Pathologic Response at the Time of Surgery as Measured by % Tumor Viability ( >= 95% Necrosis)

  An expected average of 12 weeks

• Progression Free Survival

  Up to 3 years

Study Arms (2)

Arm I (pazopanib hydrochloride)

EXPERIMENTAL

Patients receive pazopanib hydrochloride PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Doxorubicin Hydrochloride; Radiation: External Beam Radiation Therapy; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Doxorubicin Hydrochloride; Radiation: External Beam Radiation Therapy; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Procedure: Therapeutic Conventional Surgery

Interventions

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Arm I (pazopanib hydrochloride); Arm II (placebo)

External Beam Radiation Therapy RADIATION

Undergo external beam radiation therapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation

Arm I (pazopanib hydrochloride); Arm II (placebo)

Ifosfamide DRUG

Given IV

Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

Arm I (pazopanib hydrochloride); Arm II (placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (pazopanib hydrochloride); Arm II (placebo)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Arm I (pazopanib hydrochloride)

Pharmacological Study OTHER

Correlative studies

Arm I (pazopanib hydrochloride); Arm II (placebo)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Arm I (pazopanib hydrochloride); Arm II (placebo)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed soft-tissue sarcoma, excluding alveolar and embryonal rhabdomyosarcoma, well- and dedifferentiated adipocytic sarcomas, Ewing's, osteosarcoma, or gastrointestinal stromal tumor; American Joint Committee on Cancer (AJCC) (6th Edition) Stage III or T2a Stage II or Stage IV treatment naive patients planned for resection of the primary tumor, with resectable metastatic disease
• Measurable disease greater than 5 centimeters in greatest dimension; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter for non-nodal lesions and short axis for nodal lesions to be recorded) by chest x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) or with calipers by clinical exam; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)
• Intermediate or high grade lesions: 2 or 3 on a scale of 1-3 or grades 2 to 4 on a scale of 1-4
• Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on the body wall
• Life expectancy of greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Karnofsky \>= 80%
• No prior chemotherapy, radiotherapy, or antiangiogenic therapy
• Absolute neutrophil count (ANC) \>= 1500/uL
• Hemoglobin (Hgb) \>= 9.0 g/dL
• Platelets \>= 100,000/uL
• Creatinine =\< 1.5 x upper limit of normal (ULN)
• Bilirubin =\< 1.5 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 1.5 x ULN
• Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 1.2 X the ULN unless a subject is receiving Coumadin and has stable INR which is in range for the desired level of anticoagulation

You may not qualify if:

• Subjects with known brain metastases and/or unresectable sarcoma
• Uncontrolled intercurrent illness including, active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular arrhythmia requiring anti-arrhythmic therapy, serious hepatic impairment, or psychiatric illness/social situations that would limit compliance with study
• Pregnant or lactating women
• Subjects with no additional active malignancy within the last 3 years
• Subjects receiving other investigational agents
• Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study
• Subjects who have both bilirubin \> ULN and AST/ALT \> ULN
• Subjects with a urine protein/creatinine ratio greater than 1
• Subjects with a baseline corrected QT (QTc) of equal to or greater than 480 msecs or other significant electrocardiogram (ECG) abnormalities
• Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in subjects receiving pazopanib and others should be avoided or administered with extreme caution and require principal investigator (PI) approval
• Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole may increase pazopanib concentrations and are prohibited; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib
• Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib concentrations, are prohibited
• Medications which have narrow therapeutic windows and are substrates of CYP3A4, CYP2D6, or CYP2C8 should be avoided and, if necessary, administered with caution
• Pazopanib, 800 mg once daily, has no effect on CYP2C9, CYP1A2, or CYP2C19 in vivo but does in vitro; therefore, therapeutic doses of warfarin, a substrate of CYP2C9, and omeprazole, a substrate of CYP2C19 are permitted; caffeine, a substrate of CYP1A2, is also permitted
• Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin; Ifosfamide; pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr Darin Davidson
• Organization: University of Washington

djdavi@uw.edu

206-543-3690

Study Officials

• Darin Davidson

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2011
• First Posted: October 5, 2011
• Study Start: April 1, 2012
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: April 13, 2020
• Results First Posted: April 25, 2019

Record last verified: 2020-01

Locations

US (1)