| Eligibility |
Inclusion Criteria:
- Participants must have discontinued all previous treatments for cancer or
investigational agents =7 days after the last dose or per the type of previous
treatment as stated in the protocol and must have recovered from the acute effects to
=Grade 2 for alopecia and decreased tendon reflex and to =Grade 1 for all other
effects at the time of enrollment, unless otherwise noted. Consult with the Lilly
clinical research physician or scientist for the appropriate length of time prior to
the first dose of study treatment.
- Participants with relapsed, recurrent, or refractory DSRCT.
- Participants must:
- Have measurable disease by Response Evaluation Criteria in Solid Tumors, Version
(RECIST) 1.1.
- Have received at least one prior line of systemic treatment (including
neoadjuvant and adjuvant chemotherapy). This prior treatment must include
approved therapies for which they are eligible, unless the participant is not a
suitable candidate for the approved therapy.
- Not be eligible for surgical resection at time of enrollment.
- Adequate cardiac function, defined as: Shortening fraction of =27% by echocardiogram,
or ejection fraction of =50% by gated radionuclide study.
- Adequate blood pressure (BP) control, defined as:
- Participants =18 years: Controlled hypertension defined as systolic BP =150
millimeters of mercury (mmHg) or diastolic BP =90 mmHg where standard medical
management is permitted. Please note that =2 serial BP readings should be
obtained and averaged to determine baseline BP.
- Participants <18 years: A BP =95th percentile for age, height, and gender
measured as described in National High Blood Pressure Education Program Working
Group (NHBPEPWG) on High Blood Pressure in Children and Adolescents (2004), where
standard medical management is permitted. Please note that =2 serial BP readings
should be obtained and averaged to determine baseline BP.
- Adequate hematologic function, as defined as:
- Absolute neutrophil count (ANC): =750/microliters (µL) granulocyte-colony
stimulating factor (G-CSF) permitted up to 48 hours prior. Participants with
documented history of benign ethnic neutropenia or other conditions could be
considered with a lower ANC after discussion with and approval from the Lilly
clinical research physician or scientist.
- Platelets: =75,000/cubic millimeters. Platelet transfusion permitted up to 72
hours prior.
- Hemoglobin: =8 grams per deciliter (g/dL) (=80 g/liter). Transfusions to increase
the participant's hemoglobin level to at least 8 g/dL are permitted; however,
study treatment must not begin until 7 days after the transfusion, and complete
blood count criteria for eligibility are confirmed within 24 hr of first study
dose.
- Adequate renal function, as defined as:
- Creatinine clearance or radioscope glomerular filtration rate (GFR) =60
milliliters/minute/meters squared OR serum creatinine meeting the following
parameters:
- for participants =18 years of age serum creatinine =1.5×upper limit of
normal (ULN);
- for participants <18 years of age, serum creatinine based on age/gender as
follows: Age 1 to <2 years maximum serum creatinine 0.6, Age 2 to <6 years
maximum serum creatinine 0.8, Age 6 to <10 years maximum serum creatinine
1.0, Age 10 to <13 years maximum serum creatinine 1.2, Age 13 to <16 years
maximum serum creatinine 1.5 for males and 1.4 for females, Age 16 to <18
years maximum serum creatinine 1.7 for males and 1.4 for females.
- Urine protein meeting the following parameters:
- for participants =18 years of age: <2+ on dipstick or routine urinalysis. If
urine dipstick or routine analysis indicates proteinuria =2+, then a 24-hour
urine must be collected and must demonstrate <2 grams of protein in 24 hours
to allow participation in the study.
- for participants <18 years of age: =30 milligrams per deciliter urine
analysis or <2+ on dipstick. If urine dipstick or routine analysis indicates
proteinuria =2+, then a 24-hour urine must be collected and must demonstrate
<1 g of protein in 24 hours to allow participation in the study.
- Adequate liver function:
- Total bilirubin: =1.5×ULN. Except participants with document history of Gilbert
Syndrome who must have a total bilirubin level of <3.0×ULN.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): =2.5×ULN OR
=5.0×ULN if the liver has tumor involvement.
- The participant has an adequate coagulation function as defined by International
Normalized Ratio =1.5 or prothrombin time =1.5×ULN, and partial thromboplastin time
=1.5×ULN if not receiving anticoagulation therapy. For participants receiving
anticoagulants, exceptions to these coagulation parameters are allowed if they are
within the intended or expected range for their therapeutic use. Participants must
have no history of clinically significant active bleeding (defined as within 14 days
of first dose of study drug) or pathological condition that carries a high risk of
bleeding (for example, tumor involving major vessels or known esophageal varices).
- The participant has adequate hematologic and organ function =1 week (7 days) prior to
first dose of study drug.
- Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 7 days prior to randomization. Male and female participants must
agree to use highly effective contraception for the duration of the study and up to 3
months following the last dose of ramucirumab and vinorelbine, and 12 months following
the last dose of cyclophosphamide in order to prevent pregnancy.
Exclusion Criteria:
- Participants with severe and/or uncontrolled concurrent medical disease or psychiatric
illness/social situation that in the opinion of the investigator could cause
unacceptable safety risks or compromise compliance with the protocol.
- Participants who have active infections requiring therapy.
- Participants with an active fungal, bacterial, and/or known severe viral
infection including, but not limited to, human immunodeficiency virus (HIV) or
viral (A, B, or C) hepatitis (screening is not required).
- Participants who have had allogeneic bone marrow or solid organ transplant are
excluded.
- Surgery: Participants who have had, or are planning to have, the following invasive
procedures are not eligible:
- Major surgical procedure, laparoscopic procedure, or significant traumatic injury
within 28 days prior to enrollment.
- Central line placement or subcutaneous port placement is not considered major
surgery.
- Core biopsy, fine needle aspirate, and bone marrow biopsy/aspirate are not
considered major surgeries.
- Surgical or other wounds must be adequately healed prior to enrollment.
- Bleeding and thrombosis:
- Participants with evidence of active bleeding or a history of significant (=Grade
3) bleeding event within 3 months prior to enrollment are not eligible.
- Participants with a bleeding diathesis or vasculitis are not eligible.
- Participants with known or prior history in the prior 3 months of esophageal
varices are not eligible.
- Participants with a history of deep vein thrombosis requiring medical
intervention (including pulmonary embolism) within 3 months prior to study
enrollment are not eligible.
- Participants with a history of hemoptysis or other signs of pulmonary hemorrhage
within 3 months prior to study enrollment are not eligible.
- Cardiac:
- Participants with a history of central nervous system (CNS) arterial/venous
thromboembolic events (VTEs) including transient ischemic attack (TIA) or
cerebrovascular accident (CVA) within 6 months prior to study enrollment are not
eligible.
- Participants with myocardial infarction or unstable angina within the prior 6
months.
- Participants with New York Heart Association Grade 2 or greater congestive heart
failure (CHF).
- Participants with serious and inadequately controlled cardiac arrhythmia.
- Participants with significant vascular disease (eg, aortic aneurysm, history of
aortic dissection).
- Participants with clinically significant peripheral vascular disease.
- Participants who have a history of fistula, gastrointestinal (GI) ulcer or
perforation, or intra-abdominal abscess within 3 months of study enrollment are not
eligible.
- Participants with a history of hypertensive crisis or hypertensive encephalopathy
within 6 months of study enrollment are not eligible.
- Participants who have non-healing wound, unhealed or incompletely healed fracture, or
a compound (open) bone fracture at the time of enrollment are not eligible.
- Participants previously treated and progressed on combination cyclophosphamide and
vinorelbine regimen. Participants who received combination as maintenance therapy,
without progression, would be eligible.
- Participants with a known hypersensitivity to ramucirumab, cyclophosphamide,
vinorelbine or any of the excipients of the medicinal products.
- Hepatic impairment:
- Severe liver cirrhosis Child-Pugh Class B (or worse).
- Cirrhosis with a history of hepatic encephalopathy.
- Clinically meaningful ascites resulting from cirrhosis and requiring ongoing
treatment with diuretics and/or paracentesis.
- History of hepatorenal syndrome.
- The participant has a bowel obstruction, history or presence of inflammatory
enteropathy or extensive intestinal resection (eg, hemicolectomy or extensive small
intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or
chronic diarrhea.
- The participant has a urinary outflow obstruction.
- The participant has Grade 2 hematuria or non-infectious cystitis at the time of
screening.
- Participants with central nervous system (CNS) involvement are ineligible.
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