Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-Rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02180867
First received: July 1, 2014
Last updated: August 24, 2016
Last verified: August 2016
  Purpose
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 that can be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy works better when given with or without combination chemotherapy and/or pazopanib hydrochloride in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

Condition Intervention Phase
Adult Fibrosarcoma
Alveolar Soft Part Sarcoma
Angiomatoid Fibrous Histiocytoma
Atypical Fibroxanthoma
Clear Cell Sarcoma of Soft Tissue
Epithelioid Malignant Peripheral Nerve Sheath Tumor
Epithelioid Sarcoma
Extraskeletal Myxoid Chondrosarcoma
Extraskeletal Osteosarcoma
Fibrohistiocytic Neoplasm
Glomus Tumor of the Skin
Inflammatory Myofibroblastic Tumor
Intimal Sarcoma
Leiomyosarcoma
Liposarcoma
Low Grade Fibromyxoid Sarcoma
Low Grade Myofibroblastic Sarcoma
Malignant Cutaneous Granular Cell Tumor
Malignant Peripheral Nerve Sheath Tumor
Malignant Triton Tumor
Mesenchymal Chondrosarcoma
Myxofibrosarcoma
Myxoid Chondrosarcoma
Myxoinflammatory Fibroblastic Sarcoma
Nerve Sheath Neoplasm
PEComa
Pericytic Neoplasm
Plexiform Fibrohistiocytic Tumor
Sclerosing Epithelioid Fibrosarcoma
Stage IB Soft Tissue Sarcoma
Stage IIB Soft Tissue Sarcoma
Stage III Soft Tissue Sarcoma
Stage IV Soft Tissue Sarcoma
Synovial Sarcoma
Undifferentiated (Embryonal) Sarcoma
Undifferentiated High Grade Pleomorphic Sarcoma of Bone
Drug: Doxorubicin Hydrochloride
Drug: Ifosfamide
Other: Laboratory Biomarker Analysis
Drug: Pazopanib Hydrochloride
Other: Pharmacological Study
Radiation: Radiation Therapy
Procedure: Therapeutic Conventional Surgery
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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 (NSC# 737754)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • EFS (Phase III) [ Time Frame: Time to the first occurrence of progression, relapse after response, secondary cancer or death from any cause, assessed up to 60 months ] [ Designated as safety issue: No ]
    The null (radiation therapy only) 5-year EFS for patients with localized unresectable chemo-resistant tumors is expected to be about 30%.

  • Potential benefit for chemoradiotherapy plus pazopanib hydrochloride defined as protocol week 13 pathologic response (Phase II) [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
    The expected null (chemotherapy only) pathologic response rate (90%+ necrosis at week 13) is 40%.

  • Potential benefit for radiotherapy plus pazopanib hydrochloride defined as protocol week 10 pathologic response (Phase II/III) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    The expected null (radiation therapy only) pathologic response rate (90%+ necrosis at Week 10) is 10%.


Secondary Outcome Measures:
  • Adverse event profile of the treatments delivered (chemo-radiotherapy; radiotherapy) characterized using the current Common Terminology Criteria for Adverse Events version [ Time Frame: Up to 60 months ] [ Designated as safety issue: Yes ]
  • Distant failure defined as disease recurrence at sites other than the primary site and diagnosis and nodes regional to that site (metastatic disease, whether or not present at diagnosis), with or without loco-regional failure [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.

  • Local failure defined as disease recurrence only at the primary site of disease at diagnosis [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.

  • Regional failure defined as disease recurrence at lymph nodes regional to the primary disease site, with or without local failure but without distant failure [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.


Other Outcome Measures:
  • Change in FDG PET SUVmax [ Time Frame: Baseline to week 13 ] [ Designated as safety issue: No ]
  • Circulating Tumor DNA [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Descriptive analyses will be performed.

  • Frequency with which combinations of actionable mutations are observed in individual tumor types [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Descriptive statistical analyses will be estimated.

  • Pharmacokinetic parameters of doxorubicin hydrochloride and pazopanib hydrochloride [ Time Frame: Up to 48 hours after the end of infusion ] [ Designated as safety issue: No ]
    The present trial is designed to allow detection of statistically significant changes in the mean clearance of doxorubicin of at least 25% using a one-sample analysis, which concerns testing an observed experimental mean against the expected (historical) mean of 25.6 L/h/m^2.

  • Rates of actionable mutations on whole genome sequencing [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Descriptive and exploratory statistical analyses will be carried out.

  • Relative risk of failure based on both standard imaging and pathologic assessment [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Log-rank test will be used to see if one response assessment method produces a larger difference in outcome between the response categories.

  • The relative frequency of actionable mutations across the whole cohort and within more common histological subtypes, like synovial sarcoma and malignant peripheral nerve sheath tumors [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Descriptive statistical analyses will be estimated.


Estimated Enrollment: 340
Study Start Date: July 2014
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A (pazopanib hydrochloride, chemoradiation)

INDUCTION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 1-12, ifosfamide IV over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10, and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 1 and 4. Patients undergo radiation therapy on weeks 4-10.

SURGERY: Patients undergo surgery on week 13.

CONTINUATION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 16-25, ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19, and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. Patients undergo radiation therapy on weeks 16-25 for a total of 45 Gy.

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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
Drug: Ifosfamide
Given IV
Other Names:
  • 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
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Experimental: Regimen B (chemoradiation)

INDUCTION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10 and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 1 and 4. Patients undergo radiation therapy on weeks 4-10.

SURGERY: Patients undergo surgery on week 13.

CONTINUATION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19 and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. Patients undergo radiation therapy on weeks 16-25 for a total of 45 Gy.

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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
Drug: Ifosfamide
Given IV
Other Names:
  • 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
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Experimental: Regimen C (pazopanib hydrochloride, radiation therapy)

INDUCTION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7.

SURGERY: Patients undergo surgery on week 10.

CONTINUATION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 13-25. Patients undergo radiation therapy on weeks 13-16 for a total of 50 Gy.

Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Experimental: Regimen D (radiation therapy)

INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7.

SURGERY: Patients undergo surgery on week 10.

CONTINUATION PHASE: Patients undergo radiation therapy on weeks 13-16 for a total of 50 Gy.

Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgery

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed and histopathologically confirmed, potentially resectable 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
    • Notes: an incisional biopsy or core biopsy is preferred; fine needle aspiration biopsy is not acceptable to establish the diagnosis
  • 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 3 AND
  • One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):

    • 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 not otherwise specified [NOS]")
    • Synovial sarcoma
    • Angiosarcoma of soft tissue
    • Adult fibrosarcoma
    • Mesenchymal (extraskeletal) chondrosarcoma
    • Leiomyosarcoma
    • Liposarcoma (excluding myxoid liposarcoma)
    • Undifferentiated pleomorphic sarcoma
    • Embryonal sarcoma of the liver
  • Patients meeting the above criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the chemotherapy cohort or the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort
  • Patients 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 < 30 years of age
    • Synovial sarcoma
    • Embryonal sarcoma of the liver
  • ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT:
  • Patients with any size of grade 2 or 3 of the following "intermediate (rarely metastasizing)" or "malignant" tumors, as defined in the WHO classification of soft tissue tumors for which we have consensus data of chemotherapy-resistance are eligible only for the non-chemotherapy cohort:

    • So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues
    • Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma
    • Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), intimal sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor
    • Chondro-osseous tumors - extraskeletal osteosarcoma
    • Pericytic (perivascular) tumors - malignant glomus tumor
    • Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor
    • Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
  • Patients meeting the criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort; Note that tumors arising in bone are NOT eligible for this study
  • Extent of disease:

    • Patients with non-metastatic and metastatic disease are eligible
    • Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor
  • Sufficient tissue and blood must be available to submit for required biology studies
  • Lansky performance status score >= 70 for patients =< 16 years of age
  • Karnofsky performance status score >= 70 for patients > 16 years of age
  • Absolute neutrophil count >= 1500/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • Platelet count >= 100,000/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • Hemoglobin >= 8 g/dL for patients =< 16 years of age; >= 9 g/dL for patients > 16 years of age; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or normal serum creatinine based on age/gender as follows:

    • 2 to < 6 years; 0.8 mg/dL male; 0.8 mg/dL female
    • 6 to < 10 years; 1 mg/dL male; 1 mg/dL female
    • 10 to < 13 years; 1.2 mg/dL male; 1.2 mg/dL female
    • 13 to < 16 years; 1.5 mg/dL male; 1.4 mg/dL female
    • >= 16 years; 1.5 mg/dL male; 1.4 mg/dL female
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]) or serum glutamate pyruvate transaminase [SGPT] (alanine transaminase [ALT]) < 2.5 x upper limit of normal (ULN) for age
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram
  • Corrected QT interval (QTc) < 480 msec
  • 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
  • Patient must have a life expectancy of at least 3 months with appropriate therapy
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with grade 1 NRSTS tumors of any size are not eligible
  • Patients with known central nervous system (CNS) metastases are not eligible; Note: brain imaging is not an eligibility requirement
  • Patients with evidence of active bleeding or bleeding diathesis will be excluded (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 are NOT eligible; patients who have experienced tumor recurrence after a gross total tumor resection are NOT eligible
  • Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is defined as follows:

    • Patients aged =< 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height which is not controlled by one anti-hypertensive medication
    • Patients aged > 17 years: systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg that is not controlled by one anti-hypertensive medication
  • Prior Therapy:

    • Patients must have had no prior anthracycline (eg, doxorubicin, daunorubicin) or ifosfamide chemotherapy
    • Patients must have had no prior use of pazopanib or similar multi-targeted tyrosine kinase inhibitors (TKI)
    • Patients must have had no prior radiotherapy to tumor-involved sites
    • Note: 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
  • CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
  • CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible
  • CYP3A4 Inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of glucocorticoids)
  • 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
  • Subjects with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:

    • Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
    • Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
    • Active peptic ulcer disease
    • Malabsorption syndrome
  • Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:

    • Active peptic ulcer disease
    • Known intraluminal metastatic lesions
    • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
    • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
  • Subjects with any of the following cardiovascular conditions within the past 6 months

    • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
    • Cardiac arrhythmia
    • Admission for unstable angina
    • 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
  • History of serious or non-healing wound, ulcer, or bone fracture
  • 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
  • Patients who are unable to swallow whole tablets are not eligible
  • Patients with a body surface area < 0.5 m^2 are not be eligible
  • Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible
  • Patients who are receiving any other investigational agent(s)
  • Pregnancy and breast feeding:

    • Female patients who are pregnant are ineligible
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment
    • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Unwillingness to use an effective contraceptive method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with reproductive potential
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02180867

  Show 318 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Aaron Weiss Children's Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02180867     History of Changes
Other Study ID Numbers: NCI-2014-01340  NCI-2014-01340  ARST1321  ARST1321  U10CA180886  U10CA098543 
Study First Received: July 1, 2014
Last Updated: August 24, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Sarcoma
Osteosarcoma
Liposarcoma
Chondrosarcoma
Leiomyosarcoma
Sarcoma, Synovial
Histiocytoma
Fibrosarcoma
Sarcoma, Alveolar Soft Part
Nerve Sheath Neoplasms
Neurofibroma
Histiocytoma, Benign Fibrous
Neurilemmoma
Neurofibrosarcoma
Sarcoma, Clear Cell
Granuloma, Plasma Cell
Chondrosarcoma, Mesenchymal
Histiocytoma, Malignant Fibrous
Skin Neoplasms
Glomus Tumor
Granular Cell Tumor
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Adipose Tissue
Neoplasms, Muscle Tissue
Neoplasms, Fibrous Tissue
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 24, 2016