Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III, Double-Blind, Placebo-Controlled, Crossover Study Evaluating Aprepitant in Combination With a 5HT3 & Dexamethasone in Patients With Germ Cell Tumors Undergoing 5 Day Cisplatin-Based Chemotherapy Regimen
Brief Summary: Aprepitant is currently approved for prophylaxis of acute and delayed CINV for highly emetogenic chemotherapy regimens, including cisplatin; however, it has not yet been studied in multiple-day chemotherapy treatment programs. This study will compare the addition of aprepitant compared to placebo administered on days 3,4,5 of chemotherapy administration for acute CINV prophylaxis with standard antiemetic prophylaxis and days 6 and 7 for delayed CINV prophylaxis in a double-blind, randomized, crossover study design.


Options:
A: Inclusion Criteria:

* Histologic, serologic or clinical evidence of germ cell tumor.
* Patients scheduled to receive a 5 day fractionated cisplatin-based combination chemotherapy on permitted regimens
* Prior chemotherapy is allowed. Patients will be stratified based on previous treatment.
* Male patients 15 years of age or older at time of registration.
* Patient will provide written informed consent and authorization to release personal health information.

Exclusion Criteria:

* No known history of anticipatory nausea or vomiting.
* No use of another antiemetic agent within 72 hours prior to beginning chemotherapy.
* No known central nervous system (CNS) metastasis.
* No known hypersensitivity to any component of study regimen.
* No concurrent participation in a clinical trial which involves another investigational agent.
* No use of warfarin while on study.
* No use of agents expected to induce the metabolism of aprepitant which include: Rifampin, Rifabutin, Phenytoin, Carbamazepine, and barbiturates.
* No use of agents which may impair metabolism of aprepitant which include: Cisapride, macrolide antibiotics (Erythromycin, Clarithromycin, Azithromycin), azole antifungal agents (Ketoconazole, Itraconazole, Voriconazole, Fluconazole), Amifostine, Nelfinavir and Ritonavir.
B: Inclusion Criteria:

* A subject will be considered eligible for initial inclusion in this study, and progression into subsequent cycles of therapy within the study, only if all of the following criteria apply:
* Subject understands the nature and purpose of this study and the study procedures and has signed an informed consent form for this study to indicate this understanding.
* At least 18 years of age.
* Is scheduled to receive oxaliplatin at a dose between 85 mg/m² and 130 mg/m² in their first cycle of therapy for the treatment of colorectal cancer, administered as a single IV dose over 2-6 hours on Day 1 only, in combination with 5FU/LV, or in combination with capecitabine.
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Hematologic and metabolic status adequate for receiving an oxaliplatin-based moderately emetogenic regimen and meeting the following criteria:

  * Total Neutrophils ≥1500/mm³ (Standard units : ≥1.5 x 10\^9/L)
  * Platelets ≥100,000/mm³ (Standard units: ≥100.0 x 10\^9/L)
  * Bilirubin ≤1.5 x upper limit of normal (ULN)
  * Serum Creatinine ≤1.5 mg/dL (Standard units : ≤132.6 µmol/L) OR
  * Creatinine clearance ≥60 mL/min

Creatinine clearance must be calculated using the Cockcroft-Gault formula:

Clcreat (ml/min) = (140-age \[yr\]) x body wt \[kg\] 72 x serum creatinine \[mg/dl\] For females: multiply creatinine clearance by a factor of 0.85. OR Clcreat (ml/min) = K x (140-age \[yr\]) x body wt \[kg\] serum creatinine \[µmol/L\] K=1.05 for females K=1.23 for males

* Liver enzymes must be below the following limits:
* Without known liver metastases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x ULN.
* With known liver metastases: AST and/or ALT ≤5.0 x ULN.

  * Is willing and able to complete daily components of the Subject Diary for Cycle 1 and Cycle 2 without assistance from others.
  * A female subject is eligible to enter and participate in this study if she is of:

    1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses)
    2. child-bearing potential: must have a negative serum pregnancy test result or negative urine dipstick pregnancy test within 24 hours prior to the first dose of investigational product on Cycle 1 Day 1. Women of childbearing potential must also commit to consistent and correct use of an acceptable method of birth control. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:
* male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject;
* oral contraceptives (e.g., oral, injectable, or implantable) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm for a period after the trial to account for a potential drug interaction (minimum of six weeks);
* double-barrier method of contraception consisting of spermicide with either condom or diaphragm;
* intra-uterine device with a documented failure rate of less than 1% per year;
* complete abstinence from intercourse for two weeks before exposure to the investigational product throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of 3 days);
* if subject indicates they will remain abstinent during the period described above, they must agree to follow GSK guidelines for the consistent and correct use of an acceptable method of birth control should they become sexually active.

Exclusion Criteria:

* A subject will not be eligible for initial inclusion in this study if any of the following criteria apply, or will not be eligible for subsequent cycles of therapy if any of the following criteria become applicable:
* Has received cytotoxic chemotherapy prior to the first study cycle of chemotherapy, with the exception that previous adjuvant therapy with 5FU/LV or capecitabine is permitted, provided that the last dose of adjuvant therapy was completed at least 6 months prior to receiving the first dose of study medication or investigational product. Previous biological or hormonal therapy completed at any time is permitted.
* Scheduled to receive chemotherapy with any cytotoxic agents (e.g., irinotecan, gemcitabine) or biological agents (e.g., cetuximab, panitumimab) other than the protocol allowed chemotherapy described in Inclusion Criterion 3.
* Is a female subject who is pregnant or lactating.
* Has received radiation therapy in the 10 days prior to the first dose of study medication or investigational product and/or is scheduled to receive such radiation therapy in the 6 days following the first dose of study medication or investigational product in the first cycle of chemotherapy. Radiation therapy may be added in subsequent cycles of chemotherapy.
* Has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea in the 24 hours preceding the first dose of study medication or investigational product for each cycle of chemotherapy.
* Has known central nervous system metastasis, unless previously successfully treated with excision or radiation, and has been stable for at least 1 week immediately prior to receiving the first dose of study medication or investigational product.
* Has increased intracranial pressure, hypercalcemia, an active systemic infection, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV) or pose an unwarranted risk to the subject.
* Has a known hypersensitivity or contraindication to ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
* Has received an NK-1 receptor antagonist prior to the first study cycle of chemotherapy.
* Has received an investigational drug within the previous 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study medication or investigational product, or is scheduled to receive any investigational drug other than casopitant/placebo during the study period.
* Has taken/received any medication of moderate or high emetogenic potential (including antineoplastic agents \[see Appendix 2\]) within the 48 hours prior to the first dose of study medication or investigational product in each cycle. However, opioid narcotics will be permitted if the subject has been on such medication for at least 7 days at a stable dose prior to the start of each cycle, and has not experienced emesis or nausea from the narcotics.
* Has taken/received any medication with known or potential antiemetic activity within the 24-hour period (unless otherwise stated) prior to receiving the first dose of study medication or investigational product or is expected to require use of such medication during the 120 hour assessment period for Cycle 1 of therapy only. This includes, but is not limited to:

  * 5-HT3 receptor antagonists (e.g., additional ondansetron, or granisetron, dolasetron, tropisetron, ramosetron). Palonosetron is not permitted within 7 days prior to administration of study medication or investigational product;
  * benzamide / benzamide derivatives (e.g., metoclopramide, alizapride);
  * benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least 7 days prior to the first dose of investigational product; however, lorazepam is prohibited 24 hours prior to receiving study drug regardless of reason for use);
  * phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine);
  * butyrophenones (e.g., haloperidol, droperidol);
  * corticosteroids within 72 hours prior to the first dose of study medication or investigational product (e.g., dexamethasone, methylprednisolone); with the exception that topical steroids for skin disorders including eye and ear drops, and inhaled steroids for respiratory disorders at ≤ 10 mg prednisone daily or its equivalent are permitted;
  * anticholinergics (e.g., scopolamine); with the exception that anticholinergics for the treatment of respiratory disorders and the management of diarrhea (e.g., ipratropium bromide, and hyoscyamine) and anticholinergic eye drops are permitted;
  * first-generation antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine; see Appendix 4); except for topical use which is permitted;
  * domperidone;
  * cannabinoids;
  * mirtazapine;
  * olanzapine.
* Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of investigational product in each cycle of therapy.
* Has taken/received inducers of CYP3A4 and CYP3A5 within 14 days prior to the administration of investigational product in each cycle of therapy.
* Is currently taking, or plans to take the following CYP2C8 substrates at any time during the study: the anti-diabetic agent repaglinide or the diuretic torsemide.
* Is currently taking, or plans to take any of the following CYP3A4 substrates at any time during the study: astemizole, cisapride, pimozide, terfenadine.
C: Inclusion Criteria:

* Age: ≥20 years old
* Sex: Not specified
* Patients with colon/rectal cancer who first underwent FOLFOX, XELOX or SOX regimen including oxaliplatin at ≥85 mg/m2 (naive patient), or those who had already started chemotherapy and had nausea of Grade 2 or higher in the last course or an earlier course (non-naive patient).
* Stage: not specified (neoadjuvant/adjuvant chemotherapy, advanced or recurrent type are allowed)
* Combination of molecular targeted therapy: allowable
* Written informed consent for participation in the study.

Exclusion Criteria:

* Severe liver or kidney disease
* Nausea/vomiting within 24 hr prior to chemotherapy.
* Treatment with antiemetics within 24 hr prior to chemotherapy.
* Presence of factors causing nausea/vomiting other than chemotherapy (e.g. brain tumor, gastrointestinal obstruction, active peptic ulcer disease, brain metastasis)
* Presence of a disease precluding 3-day administration of dexamethasone (e.g. uncontrollable diabetes)
* Pregnant or lactating women, women who plan to become pregnant.
* Current treatment with pimozide.
* Any patient judged to be inappropriate for the study by the investigator.
D: 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

Answer: A