Please select the eligibility criteria that correspond to the clinical trial below.
Title: Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors
Brief Summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which chemotherapy regimen combined with radiation therapy and/or surgery is more effective in treating Ewing's sarcoma or primitive neuroectodermal tumor.

PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy regimens combined with radiation therapy and/or surgery in treating patients who have Ewing's sarcoma or primitive neuroectodermal tumor.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically confirmed localized Ewing's sarcoma or peripheral primitive neuroectodermal tumor (PNET) of the bone or soft tissues

  * Diagnostic biopsy of primary tumor within 30 days of study
* Paraspinal or bony skull tumors of extradural origin allowed

  * No intradural soft tissue tumors
* Askin's tumor of the chest wall allowed

  * Chest wall tumors with ipsilateral pleural effusions or ipsilateral pleural-based secondary tumor nodules allowed
  * No contralateral pleural effusions
* No metastatic disease or distant node involvement

  * One pulmonary or pleural nodule greater than 1 cm in diameter OR more than 1 nodule greater than 0.5 cm in diameter are considered pulmonary metastasis
  * Solitary lung nodules of 0.5-1 cm OR multiple nodules of 0.3-0.5 cm allowed unless biopsy positive for tumor
* Light microscopic appearance (hematoxylin and eosin stained) consistent with Ewing's sarcoma or peripheral PNET
* No immunohistochemical or ultrastructural evidence of rhabdomyosarcoma
* No esthesioneuroblastoma
* Clinically or pathologically involved regional lymph nodes allowed
* No CNS involvement

PATIENT CHARACTERISTICS:

Age:

* 50 and under at diagnosis

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin no greater than 1.5 mg/dL

Renal:

* Creatinine normal for age
* Creatinine clearance or isotope glomerular filtration rate at least 75 mL/min

Cardiovascular:

* Shortening fraction at least 28% by echocardiography OR
* Ejection fraction at least 55% by radionuclide angiogram

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other prior malignancy except skin cancer diagnosed at least 5 years ago and currently in remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior immunotherapy for skin cancer
* No concurrent sargramostim (GM-CSF)
* No concurrent pegfilgrastim

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy

Surgery:

* Prior complete or partial excision of primary tumor allowed
B: DISEASE CHARACTERISTICS:

* Histologically confirmed soft tissue sarcoma

  * Locally advanced unresectable\* OR metastatic disease
  * High-grade (grade 2-3) disease according to the FNLCC grading system NOTE: \*Disease that could prove resectable (including pulmonary metastasectomy) after a response to chemotherapy is allowed
* The following tumor types are eligible:

  * Malignant fibrous histiocytoma
  * Myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma
  * Pleomorphic rhabdomyosarcoma
  * Synovial sarcoma
  * Myxofibrosarcoma, intermediate and high-grade
  * Fibrosarcoma
  * Leiomyosarcoma
  * Angiosarcoma
  * Malignant peripheral nerve sheath tumor
  * Epithelioid sarcoma
  * Alveolar rhabdomyosarcoma
  * Unclassifiable sarcoma, not otherwise specified
* The following tumor types are not eligible:

  * Gastrointestinal stromal tumor
  * Mixed mesodermal tumor
  * Chondrosarcoma
  * Malignant mesothelioma
  * Neuroblastoma
  * Osteosarcoma
  * Ewing's sarcoma/primitive neuroectodermal tumor
  * Desmoplastic small round cell tumor
  * Embryonal rhabdomyosarcoma
  * Alveolar soft part sarcoma
* Must have a measurable lesion with clinical evidence of progression within the past 6 weeks

  * Osseous lesions and pleural effusions are not considered measurable
* No known or symptomatic CNS metastases

PATIENT CHARACTERISTICS:

Age

* 18 to 60

Performance status

* WHO 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 1.8 mg/dL
* Albumin at least 2.5 g/dL

Renal

* Creatinine no greater than 1.4 mg/dL OR
* Creatinine clearance greater than 65 mL/min

Cardiovascular

* No history of cardiovascular disease

Other

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other severe medical illness
* No psychosis
* No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
* No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up schedule

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy for advanced or metastatic disease
* Prior adjuvant chemotherapy allowed provided there was no disease progression within 6 months after completion of treatment

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy to the sole index lesion

Surgery

* Not specified
C: Inclusion Criteria:

* Histologically or cytologically confirmed MM
* Have received only one prior systemic chemotherapy platinum-based regimen for advanced MM
* Measurable disease, defined at least 1 unidimensionally measurable lesion \> 20 mm by conventional techniques or \> 10 mm by spiral CT scan (modified RECIST criteria)
* Disease not amenable to curative surgery
* No known brain metastasis
* Age 18 and over
* Performance status 0-2
* Life expectancy \> 12 weeks
* Adequate hematologic, hepatic and renal function
* Platelet count \> 75000/mm3
* Absolute granulocyte count \> 1000/mm3
* Hemoglobin \> 9 g/dL
* Bilirubin total \< 1.5 x ULN (Upper limited normal), except patients with documented Gilbert's syndrome, who must have a total bilirubin \< 3.0 mg/dl
* AST and ALT \< 2.5 x ULN ( \< 5 x ULN if documented liver metastasis are present)
* Creatinine level \< 2mg/dl or calculated creatinine clearance \> 60 mL/min as determined by the Cockcroft Gault equation.
* Not pregnant or nursing
* Fertile patients must use effective contraception
* Patient must be willing and able to provide written informed consent, and the trial have to be approved by the institutional review board at each institution

Exclusion Criteria:

* Symptomatic chronic inflammatory or autoimmune disease
* Active hepatitis B or C
* Prior treatment with tremelimumab or other anti-CTLA-4 antibody or anti-PD1, anti-PDL-1 agents
* Clinically relevant cardiovascular disease
* History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent
* Uncontrolled active infections
* Other concurrent chemotherapy, immunotherapy, radiotherapy or investigational agents
* History of other malignancies except for adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma of cervix, unless the patient has been disease-free for at least 5 years
D: Inclusion Criteria:

* Patients with histologically documented and not surgically resectable or metastatic high-grade osteosarcoma which progressed after first or second line treatments for relapsing disease
* Measurable disease as defined by RECIST criteria vs. 1.1 (bone lesions are allowed). Baseline evaluations must be completed within 28 days prior to enrollment
* Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1. ECOG PS 2 patients are eligible if the PS 2 depends solely on orthopedic problems
* Estimated life expectancy of at least 3months
* Age≥18 years
* Adequate bone marrow, liver and renal function: Hemoglobin\>9.0g/dl, Absolute neutrophil count\>1,500/mm3, Platelet\>100,000/μl Total bilirubin\<1.5 times the upper limit of normal (ULN), ALT and AST\<2.5xULN (\<5xULN for patients with liver involvement of their cancer), PT-INR/PTT\<1.5xULN, Serum creatinine\<2xULN
* Written informed consent

Exclusion Criteria:

* Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
* Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function.
* History of HIV infection and active clinically serious infections (\>grade 2 according to NCI-CTCAE vs. 4.0)
* Symptomatic metastatic brain or meningeal tumors (unless the patient is \>6months from definitive therapy, has a negative imaging study within 4weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
* Patients with seizure disorders requiring medication
* Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7days of the start of treatment. Both men and women must use adequate barrier birth control measures during the course of the trial and 8weeks after last dose of study drug
* Patients with evidence or history of bleeding diathesis
* Patients undergoing renal dialysis
* Patients unable to swallow oral medications
* Uncontrolled diabetes (fasting glucose\>2xULN)
* Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤20mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for ≥4weeks prior to the first dose of Everolimus. Topical or inhaled corticosteroids are permitted
* Patients with a history of another malignancy within 5years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer skin or other solid tumors curatively treated with no evidence of disease for ≥3years. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
* Anticancer chemotherapy or immunotherapy during the study or within 4weeks of study entry
* Radiotherapy during study or within 3weeks of start of study drug. (Palliative radiotherapy will be allowed)
* Major surgery within 4weeks of start of study
* Investigational drug therapy outside of this trial during or within 4weeks of study entry
* Prior exposure to the study drugs or their analogues
* Patients with known hypersensitivity to sorafenib, everolimus or other rapamycin analogs, or to its excipients
* Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
* A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits

Answer: A