Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Parallel-Group Study, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of a Single 150 mg Dose of Intravenous Fosaprepitant Dimeglumine for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Moderately Emetogenic Chemotherapy
Brief Summary: This study aims to demonstrate that, when given concomitantly with a 5-hydroxytryptamine 3 (5-HT3) antagonist and a corticosteroid, a single 150 mg intravenous (IV) dose of fosaprepitant given on Day 1 is superior to the control regimen of 5-HT3 antagonist and corticosteroid only, in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC).


Options:
A: Inclusion Criteria:

* Patient has been diagnosed with histologically or cytologically confirmed solid cancer
* Starting with first cycle of chemotherapy of moderate emetogenic risk, which does not include a combination of anthracycline plus cyclophosphamide
* Age ≥ 18
* WHO ≤ 1
* Patient is able to understand and speak Dutch

Exclusion Criteria:

* Patient with nausea and/or vomiting in 48 hours before start of chemotherapy treatment
* Patient submitted to concomitant radiotherapy or submitted to radiotherapy 15 days before start of chemotherapy or planned to receive radiotherapy during 8 days after administration of chemotherapy
* Patient with concomitant severe comorbidy, such as: o Intestinal obstruction o Active peptic ulcer o Hypercalcemia o Uncontrolled diabetes mellitus o Pheochromocytoma o Tardive dyskinesia o Epilepsia o Active infective diseases o Brain - or leptomeningeal metastases o Psychiatrical disorders o Parkinsonism
* Current use of corticosteroids (similar to prednisone ≥ 10 milligrams per day)
* Current alcohol abuse
* Pregnancy
B: Inclusion Criteria:

* Male or female
* 18 years of age
* A female is eligible to enter and participate in this study if she is of:

  1. Non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had at least one of the following:

     * Has had a hysterectomy, or
     * Has had a bilateral oophorectomy (ovariectomy), or
     * Has had a bilateral tubal ligation, or • Is considered post-menopausal (defined as amenorrheic for ≥ 1 year) and having serum follicle stimulating hormone (FSH) and serum estradiol concentrations consistent with post-menopausal status.
  2. Childbearing potential, has a negative serum pregnancy or negative urine pregnancy test within 24 hours prior to administration of the first dose of study medication and agrees to one of the following:

     * Complete abstinence from sexual intercourse from two weeks prior to administration of the first dose of investigational product until 30 days after the final dose of study medication.
     * Use double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm) from two weeks prior to administration of the first dose of investigational product until 30 days after the final dose of study medication.
     * Vasectomized partner who has been documented to be sterile prior to the female subject's entry and is the sole sexual partner for that female.
     * NOTE: if women of childbearing potential are enrolled, they must use double-barrier contraception in addition to oral contraceptives during the active study treatment period until 6 weeks after the final dose of study medication.
* Histologically confirmed malignant solid tumor and is scheduled to receive at least 2 courses of chemotherapy with docetaxel as a single intravenous dose of 20 to 40 mg/m2 given over a duration of one hour and repeated weekly.
* Received eight or fewer previous doses of docetaxel. Subjects that have received more than eight doses of docetaxel must receive permission from the GSK medical monitor in order to be eligible for the study.
* ECOG performance status score of less than or equal to 2

NOTE: If the subject's performance status deteriorates between the screening Visit and the time of first dose of study drug to a score \> 2, the subject will be excluded from the study

* Adequate hematologic and other physiological organ function as evidenced by Absolute Neutrophil Count ≥1500/mm3. Platelets ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL Serum creatinine \< 1.5 mg/dL Total Bilirubin ≤ upper limit of the reference range Aspartate Transaminase (AST) \< 2 x upper limit of the reference range Alanine Transaminase (ALT) \< 2 x upper limit of the reference range Alkaline Phosphatase \< 2.5 x upper limit of the reference range. Calculated creatinine clearance \> 50 mL/min (measured by Cockcroft Gault Formula;)
* Written informed consent is obtained prior to any study-specific procedures or assessments.
* Able to swallow and retain oral medications.

Exclusion Criteria:

* Pregnant or lactating.
* Received radiation therapy to the abdomen or the pelvis in the 28 days prior to receiving the first dose of study medication or that are scheduled to receive radiation therapy to the abdomen or the pelvis in the six days following the first dose of study medication.
* Received a dose of docetaxel during the week prior to Day -1.
* Known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been stable for at least 3 months prior to receiving the first dose of study medication.
* Active systemic infection or any poorly controlled medical condition (other than malignancy) which, in the opinion of the investigator, may confound the results of the study or pose an unwarranted risk to the subject. Subjects with a previous, but not current, history of alcoholism may be permitted provided that, in the investigator's opinion, the subject's disease state will not confound the results of the study.
* Receiving regular treatment with high dose systemic corticosteroid therapy or steroid dose within 72 hours prior to receiving the first dose of study medication. Topical steroids and inhaled corticosteroids with a steroid dose of less than or equal to 10 mg prednisone daily (or its equivalent) are permitted if the subject has been on this dose for at least 14 days prior to dosing.
* Hypersensitivity or contraindication to ondansetron or other 5-HT3 receptor antagonist, dexamethasone, docetaxel, casopitant, or any component of the above mentioned medications.
* Received an investigational drug within the 28 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication, or is scheduled to receive any investigational drug during the study.
* Use of strong inhibitors of CYP3A4 or CYP3A5 prior to the first dose of study medication
* Use of inducers of CYP3A4 or CYP3A5 (other than steroids described in Exclusion Criteria 5) within 14 days prior to the first dose of study medication
* Use of drugs with a narrow therapeutic index that interact with the P-glycoprotein pathway within 14 days prior to the first dose of study medication until 14 days after the last dose of docetaxel including digoxin.
* Use of drugs with a narrow therapeutic index that are metabolized by CYP2C8 within 14 days prior to the first dose of study medication including repaglinide and torsemide.
* Disease that will significantly affect absorption of oral medications.
* Inadequate venous access for pharmacokinetic sampling.
* Unresolved Grade 2 or worse toxicity from prior therapy.
* Active peptic ulcer disease (PUD) or a history of PUD of unknown etiology. NOTE: Subject is eligible to enter and participate in this study if they have a history of PUD of known etiology with documentation from a gastroenterologist or other qualified physician of the etiology of the PUD and that effective treatment was provided with full eradication of ulcers and symptoms. Subjects who present with symptoms of gastroesophageal reflux disease (GERD) are eligible. However, if the investigator suspects PUD in such a subject, the subject must have a GI assessment to rule out PUD. If assessment is negative, subject may enter the study. For these subjects, appropriate steps must also have been taken to minimize the risk of reoccurrence. If PUD was non-steroidal anti-inflammatory drug (NSAID) induced, the subject should no longer be taking NSAID medication(s). If PUD was induced by H. pylori, the subject should have been appropriately treated.
* Stool positive for occult blood. Test may be repeated once if subject did not abstain from red meat for the previous three days.
* Pepsinogen level below the lower limit of laboratory reference range (LLRR).
* Troponin level above 10% of the coefficient of variation of the assay as determined by the laboratory performing the test.
* Calculated QT interval (QTc) \> 480 msecs.
* Clinically significant cardiac disease that would interfere with participation in the study as determined by the investigator.
* Known or suspected iron deficiency.
* Use of NSAIDS, including aspirin at any dose, and including COX2 inhibitors. These medications are prohibited 7 days prior to administration of study drug and for the duration of the study until 72 hours after the last dose of study drug.
C: Inclusion Criteria:

* Histologically or cytologically confirmed malignant disease
* Scheduled to receive a single dose of one or more of moderately emetogenic chemotherapeutic agents during Cycle 1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 or Karnofsky score ≥60
* Predicted life span ≥4 months
* Laboratory values demonstrating adequate hematologic status
* Premenopausal females must not be pregnant or lactating and must agree to use effective birth control

Exclusion Criteria:

* Received chemotherapy within 6 months prior to starting on study drugs
* Scheduled to receive subsequent treatment due to a refractory response to first or second line chemotherapy
* Received an investigational drug within 30 days prior to starting on study drugs
* Radiation therapy to the abdomen or pelvis in the week prior to starting on study drugs
* Vomiting in the 24 hours prior to starting on study drugs
* Active infection (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy
* Known hypersensitivity to Aprepitant (EMEND®), Dexamethasone or 5-HT3 receptor antagonists
* Presentation with gastrointestinal obstruction symptoms
* Symptomatic primary or metastatic central nervous system malignancy
D: Inclusion Criteria:

* Has a histologically or cytologically confirmed malignant disease
* Is naive to moderately and highly emetogenic chemotherapy
* Is scheduled to receive a single IV dose of one or more MEC agents on Day 1, except for the combination of anthracycline and cyclophosphamide
* Has a predicted life expectancy of at least 4 months, and a Karnofsky score of at least 60 indicating that the participant requires occasional assistance, but is able to care for most of his/her needs.
* Female of childbearing potential demonstrates a negative urine pregnancy test, and agrees to remain abstinent or use two acceptable forms of birth control for at least 14 days prior to study, throughout the study, and at least 1 month following last dose of study drug.

Exclusion Criteria:

* Has vomited in the 24 hours prior to treatment Day 1
* Has symptomatic primary or metastatic symptomatic central nervous system malignancy causing nausea and/or vomiting
* Is scheduled to receive chemotherapy agent classified as highly emetogenic
* Has received or will receive total body irradiation, or radiation therapy to the abdomen, pelvis, head and neck in the week prior to Treatment Days 1 through Day 6 of the Treatment Period
* Has illness or history of illness which might confound study results or pose unwarranted risk
* Known history of QT interval prolongation
* Uses illicit drugs or abuses alcohol
* Mentally incapacitated or has a significant emotional or psychiatric disorder
* History of hypersensitivity to aprepitant, ondansetron or dexamethasone
* Pregnant or breast-feeding
* Has participated in a study with aprepitant or taken a non-approved (investigational) drug within the last 4 weeks
* Has concurrent condition, such as systemic fungal infection or uncontrolled diabetes, that precludes administration of dexamethasone.

Answer: D