Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, MultiCenter, Randomized, Placebo-Controlled, Double-Blind, Dose Finding Study to Determine the Safety and Efficacy of SCH 619734 for the Treatment of Chemotherapy Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)
Brief Summary: This is a Phase 2, randomized, multicenter, parallel-group, double-blind, placebo-controlled study of various doses of SCH 619734 in subjects receiving cisplatin-based chemotherapy. Ondansetron and dexamethasone will be concurrently administered with SCH 619734 before initiation of chemotherapy on Day 1. Subjects will record nausea and vomiting in the SPNV Subject Diary through Day 6. The quality of life assessment as measured by the Functional Living Index-Emesis Questionnaire (FLIE) will be used to measure the effect of chemotherapy-induced nausea and vomiting (CINV) on daily life. Blood samples for SCH 619734 pharmacokinetic assessments will be collected. The study is to be conducted in conformance with Good Clinical Practice.


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:

* 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.
D: Inclusion criteria:

* Have a diagnosis of cancer and be chemotherapy naive.
* Must be scheduled to receive a chemotherapy treatment containing doxorubicin hydrochloride, epirubicin hydrochloride, cisplatin, carboplatin, or oxaliplatin (any dose or schedule) without concurrent radiotherapy or interferon treatment
* Chemotherapy may be for adjuvant, neoadjuvant, curative or palliative intent.
* Dose-dense regimens (e.g. chemotherapy with doxorubicin or epirubicin given every two weeks)are allowed.
* For the purposes of this study, Day 1 of chemotherapy will be defined as the day of administration of cisplatin, carboplatin, oxaliplatin, doxorubicin or epirubicin.
* Regimens with multiple-day doses of doxorubicin, epirubicin, cisplatin, carboplatin, oxaliplatin, dacarbazine, hexamethylmelamine, nitrosoureas, or streptozocin are not allowed. Chemotherapy agents, other than those listed above, may be given orally, intravenously, or by continuous infusion on one or multiple days.
* Able to understand English

Exclusion criteria:

* No symptomatic brain metastases
* No concurrent or impending bowel obstruction
* Regimens containing liposomal doxorubicin or cisplatin are not allowed.
* No concurrent pimozide, terfenadine, astemizole, or cisapride
* No concurrent doxorubicin hydrochloride liposome or cisplatin
* No concurrent multiple-day doses of dacarbazine, altretamine, nitrosoureas, streptozocin, cisplatin, carboplatin, or oxaliplatin

Answer: C