Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised, Placebo Controlled, Single-center, Double-blind Clinical Trial to Investigate Efficacy and Safety of Aprepitant Combined With Kevatril and Dexamethasone Versus Placebo Combined With Kevatril and Dexamethasone in Prevention of Acute and Delayed High-dose Chemotherapy-induced Nausea and Vomiting in Subjects With Multiple Myeloma Receiving an Autologous Peripheral Blood Stemcell Transplantation.
Brief Summary: 1. Scientific background In patients with multiple myeloma high-dose chemotherapy followed by autologous stemcell transplantation is preferred to conventional therapy, since the superiority in respect to complete remission, complete remission duration, event-free survival and overall survival has been proven within well controlled clinical trials (Fassas et al., 2002; Goldschmidt et al., 2003).

   Nausea and vomiting are well known and the most distressing side-effects of a high dose chemotherapy regimen. The administration of selective 5-HT3-receptor antagonists (5-HT3 RAs) in combination with a corticosteroid (= antiemetic standard therapy) is effective for the prevention of those adverse effects in 70 to 80 % of patients. However, 25 to 40 % of the patients still suffer from vomiting and nausea in the delayed phase of the chemotherapy. Superior protection could be achieved with the addition of Aprepitant (EMEND®) to the antiemetic standard therapy in acute and delayed phases of highly emetogenic chemotherapies. The enhanced antiemetic protection can be maintained over multiple chemotherapy-cycles to an extent superior to that of standard therapy alone (de Wit et al., 2003).

   Furthermore addition of Aprepitant (EMEND®) to standard therapy was generally well tolerated and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life was significantly reduced (Hesketh et al., 2003; Dando \& Perry, 2004).
2. Trial Rationale Aprepitant (EMEND®) is a selective high-affinity receptor antagonist of human substance P/neurokinin-1 (NK1) and has been shown to inhibit emesis induced by cytotoxic chemotherapeutic agents and augments the antiemetic activity of 5-HT3 RAs (e.g. Granisetron, Ondansetron) and corticosteroids (e.g. Dexamethasone). Thus Aprepitant (EMEND®) in addition to antiemetic standard therapy has been shown to possess powerful superior protection and has been reported in several clinical trials to significantly improve both acute and delayed CINV.

The aim of this study is to evaluate, during and up to 7 days after high-dose chemotherapy with Melphalan (moderate emetogenic drug) followed by autologous peripheral blood stemcell transplantation, an antiemetic treatment regimen in respect to efficacy and safety in patients with multiple myeloma. To the best of our knowledge effects of Aprepitant on Melphalan induced CINV have never been investigated.


Options:
A: Inclusion Criteria:

* Patients will be naive to emetogenic chemotherapy with histologically or cytologically confirmed malignant disease scheduled to receive a single dose of moderately emetogenic chemotherapy on study day 1
* Karnofsky score of 60 or greater

Exclusion Criteria:

* Patient is scheduled to receive any dose of cisplatin
* Patient will receive abdominal or pelvic radiation a week prior and up to 6 days after initiation of chemotherapy
* Any allergies to study drug or antiemetics
* Taking CYP3A4 substrates/prohibited medication
* Significant medical or mental conditions
* Abnormal laboratory values (platelets, absolute neutrophils, AST, ALT, bilirubin or creatinine).
B: Inclusion Criteria:

* Men and women \>/= 18 years
* Patients with multiple myeloma receiving high-dose chemotherapy (Melphalan) and autologous peripheral stemcell transplantation
* Signed informed consent

Exclusion Criteria:

* Patients suffering from nausea and vomiting during the last 12 hours prior to planned high-dose chemotherapy
* Patients receiving antiemetics 24 hours prior to planned high-dose chemotherapy
* Intake of steroids
* History of hypersensitivity to the investigational product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product
* Simultaneous intake of pimozide, terfenadine, astemizole
* Pregnant or nursing woman
* Mental condition rendering the subject incapable to understand the nature, scope and possible consequences of the trial
* Expected non-compliance in completing the subject´s diary and FLIE-score
C: 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.
D: Inclusion Criteria:

* Subject is 18 years of age or older.
* Subject has never been treated with cisplatin and is to receive first course of cisplatin-based chemotherapy (\>=70 mg/m\^2).
* Subject has a Karnofsky performance score of \>=60.
* Subject has a predicted life expectancy of \>=3 months.
* Subject has adequate bone marrow, kidney, and liver function as evidenced by:

  * Absolute neutrophil count \>=1,500/mm3 and white blood cell count \>=3,000/mm3.
  * Platelet count \>=100,000/mm3.
  * Aspartate aminotransferase (AST) \<=2.5 x upper limit of normal (ULN) range.
  * Alanine aminotransferase (ALT) \<=2.5 x ULN.
  * Bilirubin \<=1.5 x ULN, except for subjects with Gilbert's syndrome.
  * Creatinine \<=1.5 x ULN.
* Subject is able to read, understand, and complete the questionnaires.

Exclusion Criteria:

* Any current treatment or medical history (eg, subject is mentally incapacitated or has a psychiatric disorder) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject.
* Subject has contraindication to the administration of cisplatin, ondansetron, or dexamethasone including, but not limited to, a history of hypersensitivity to the drugs or their components, severe renal impairment, severe bone marrow suppression, hearing impairment, or systemic fungal infection.
* Subject is scheduled to receive any other chemotherapeutic agent with an emetogenicity level of 3 or above (Hesketh Scale) from Day -2 through Day 6.
* Subject is scheduled to receive any radiation therapy to the abdomen or pelvis within 5 days prior to and/or during Days 1 through 5 following cisplatin infusion.
* Subject has symptomatic primary or metastatic central nervous system (CNS) disease.
* Subject has ongoing vomiting caused by any etiology or has a history of anticipatory nausea and vomiting.

Answer: B