Clinical Trial 18937

Cancer Type: Sarcoma
Interventions:Adriamycin (doxorubicin); Ifosfamide; Not Applicable; Pazopanib; doxorubicin

Study Type: Treatment
Phase of Study: Phase II/III
Investigators:


    Overview

    Study Title

    Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib

    Summary

    This randomized phase II/III trial studies how well pazopanib hydrochloride, combination chemotherapy, and radiation therapy work and compares it to radiation therapy alone or in combination with pazopanib hydrochloride or combination chemotherapy in treating patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) that can be removed by surgery.

    Objective

    Primary Objectives: - To identify the dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk NRSTS. - To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative chemoradiation alone for potentially resectable > 5 cm, Grade 3 intermediate to high risk chemotherapy-sensitive NRSTS in the Phase II portion of the study for this cohort. - To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the Phase II portion of the study for this cohort (using a Phase II decision rule to go onto the Phase III portion of the study). - To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the Phase III portion of the study for this cohort if the Phase II decision rule is passed.

    Inclusion Criteria

  • Newly diagnosed and histopathologically confirmed, potentially resectable Non-rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS) of the extremity and trunk will be eligible for the chemotherapy or non-chemotherapy cohort based on: Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based on existing evidence from prior clinical trials; Sufficient risk of metastatic disease to warrant chemotherapy based on size and grade and; Medically deemed able or unable to undergo chemotherapy.
  • ELIGIBLE SITES - Extremities: upper (including shoulder) and lower (including hip), Trunk: body wall.
  • INELIGIBLE SITES - Head and neck, visceral organs (with the exception of embryonal sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis.
  • ELIGIBILITY FOR CHEMOTHERAPY COHORT: Stage T2a/b (> 5 cm) and grade 2 or 3 AND; meet chemosensitive histology criteria as outlined in the protocol documentation.
  • Potential participants with the following histologies are only eligible for the chemotherapy cohort and cannot enroll on the non-chemotherapy cohort: Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma NOS") in patients > ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT: Patients with any size of grade 2 or 3 of the "intermediate (rarely metastasizing)" or "malignant" tumors, as defined in the WHO classification of soft tissue tumors and outlined in the protocol documentation.
  • Extent of disease: Patients with non-metastatic and metastatic disease; Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor.
  • Lansky performance status score >= 70 for patients less than or equal to 16 years of age
  • Karnofsky performance status score >= 70 for patients > 16 years of age
  • Adequate bone marrow function
  • Adequate Creatinine clearance or radioisotope glomerular filtration rate or normal serum creatinine based on age/gender
  • Adequate hepatic function
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram
  • Corrected QT interval (QTc) > No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading > 94% on room air if there is clinical indication for determination
  • Patients on low molecular weight heparin or Coumadin (with a stable international normalized ratio [INR]) are eligible
  • Must have a life expectancy of at least 3 months with appropriate therapy

  • Exclusion Criteria

  • Grade 1 NRSTS tumors of any size
  • Known central nervous system (CNS) metastases (Note: brain imaging is not an eligibility requirement)
  • Evidence of active bleeding or bleeding diathesis (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible)
  • Patients with gross total resection of the primary tumor prior to enrollment on ARST1321; patients who have experienced tumor recurrence after a gross total tumor resection
  • Uncontrolled hypertension as outlined in the study protocol
  • Prior Therapy: prior anthracycline (e.g., doxorubicin, daunorubicin) or ifosfamide chemotherapy
  • Prior use of pazopanib or similar multi-targeted tyrosine kinase inhibitors (TKI)
  • Prior radiotherapy to tumor-involved sites
  • Patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded
  • Other types of invasive malignancy that are not disease free within 3 years except for non-melanoma skin cancer, lentigo maligna, any carcinoma-in-situ or prostate cancer with low risk factors
  • Any condition that may impair the ability to swallow or absorb oral medications/investigational product
  • Cardiovascular conditions within the past 6 months, as outlined in the study protocol
  • History of serious or non-healing wound, ulcer, or bone fracture
  • Uncontrolled intercurrent illness Patients with a body surface area > Receiving any other investigational agent(s)
  • Pregnant or breastfeeding
  • Additional criteria may apply