Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Parallel-Group Study Conducted Under In-House Blinding Conditions to Determine the Safety, Tolerability and Efficacy of Aprepitant Regimen Compared to Ondansetron Regimen for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) Associated With High Dose Cisplatin in Cycle 1
Brief Summary: A multicenter trial to assess the safety and efficacy of an investigational drug in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with confirmed solid tumors who will be treated with a chemotherapy regimen that includes cisplatin. The study will evaluate the investigational drug for the treatment of CINV during the first cycle of treatment with cisplatin.


Options:
A: Inclusion Criteria:

* Signed written informed consent.
* Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted.
* Diagnosed with a malignant tumor.
* If scheduled to receive repeated consecutive courses of chemotherapy, a single dose of one or more of the following agents administered on Day 1 is allowed:

  * Highly emetogenic chemotherapy: any I.V. dose of cisplatin, mechlorethamine, streptozocin, cyclophosphamide more or equal to 1500 mg/m2, carmustine, dacarbazine;
  * Moderately emetogenic chemotherapy: any I.V. dose of oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin, cyclophosphamide I.V. (less than 1500 mg/m2), cytarabine I.V. (more than 1 g/m2), azacidine, alemtuzumab, bendamustine, or clofarabine.
* If scheduled to receive combination regimens, the most emetogenic agent is to be given as first on Day 1 and the infusion must be completed within 6 hours.
* If scheduled to receive chemotherapy agents of minimal to low emetogenic potential, they are to be given on Day 1 following the most emetogenic agent or on any subsequent study day.
* ECOG Performance Status of 0, 1, or 2
* Female patients of either non-childbearing potential or child-bearing potential with a commitment to use contraceptive methods throughout the clinical trial
* Hematologic and metabolic status adequate for receiving a moderately emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance)

Exclusion Criteria:

* If female, lactating or pregnant
* Current use of illicit drugs or current evidence of alcohol abuse.
* Scheduled to receive either cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. doxorubicin (more or equal to 40 mg/m2) or cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. epirubicin (more or equal to 60 mg/m2).
* Scheduled to receive moderately or highly emetogenic chemotherapy from Day 2 to Day 5 following Day 1 chemotherapy administration.
* Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient.
* Known hypersensitivity or contraindication to 5-HT3 receptor antagonists or dexamethasone.
* Previously received an NK1 receptor antagonist
* Participation in a clinical trial involving oral netupitant administered in combination with palonosetron.
* Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 1, and/or is scheduled to receive any investigational drug during the study.
* Systemic corticosteroid therapy at any dose within 72 hours prior to Day 1 of cycle 1. Topical and inhaled corticosteroids with a steroid dose of less or equal to 10 mg of prednisone daily or its equivalent are permitted. Non-study drug dexamethasone as pre-medication in patients scheduled to receive taxanes is allowed.
* Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
* Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1 week prior to Day 1
* Scheduled to receive any of the following CYP3A4 substrates: terfenadine, cisapride, astemizole, pimozide.
* Scheduled to receive any CYP3A4 inducer or its intake within 4 weeks prior to Day 1
* History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
* History of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome).
* Severe cardiovascular diseases within 3 months prior to Day 1, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure and severe uncontrolled arterial hypertension.
* Any illness or condition that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient.
* Concurrent medical condition that would preclude administration of dexamethasone for 4 days such as systemic fungal infection or uncontrolled diabetes.
B: Inclusion criteria:

* 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.
* Males or females of at least 18 years of age.
* Diagnosed with a malignant solid tumor and is scheduled to receive their first course of cytotoxic chemotherapy with cisplatin administered as a single intravenous dose of ≥ 70mg/m² over 1-4 hours on study Day 1, either alone or in combination with other chemotherapeutic agents. For combination regimens, non-cisplatin agents of moderate to high emetogenic potential will be allowed, but must be administered following the cisplatin infusion and be completed no more than 6 hours after the initiation of the cisplatin infusion. Chemotherapy agents of minimal to low emetogenic potential may be given on Day 1 following cisplatin or on any subsequent study day. Taxanes (e.g. paclitaxel, docetaxel) may be administered on study Day 1 only following cisplatin.
* Has an ECOG Performance Status of 0, 1, or 2.
* Hematologic and metabolic status must be adequate for receiving a highly emetogenic cisplatin-based regimen and meet the following criteria:

  * Total Neutrophils ≥ 1500/mm³ (Standard units : ≥1.5 x 10\^9/L)
  * Platelets ≥ 100,000/mm (Standard units: ≥100.0 x 10\^9/L)
  * Bilirubin ≤ 1.5 x 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) = (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 upper limit of normal.
* With known liver metastases: AST and/or ALT ≤ 5.0 x upper limit of normal.

  * Is willing and able to complete daily components of the subject diary for each study cycle.
  * Women of childbearing potential; must 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 a physician, are as follows:

    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 of cycle 1 day 1, and agrees to one of the following:
* 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 (IUD) 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 three days)
* if subjects indicate 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.

obstruction

Exclusion criteria:

* Has previously received cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
* Is scheduled to receive cisplatin treatment on more than one day during a single cycle of therapy.
* If female, is pregnant or lactating.
* Has received radiation therapy to the thorax, head \& neck, abdomen, or the pelvis in the 10 days prior to receiving the first dose of study medication and/or will receive radiation therapy to the thorax, head \& neck, abdomen or the pelvis in the 6 days following the first dose of study medication.
* Emesis (i.e. vomiting and/or retching) experienced in the 24 hours prior to receiving the first dose of study medication.
* Clinically significant nausea (e.g. ≥25 mm on a VAS) in the 24 hours prior to receiving the first dose of study medication.
* A known central nervous system primary or malignancy metastatic to the CNS, unless successfully treated with excision or radiation and subsequently has been stable for at least 1 week prior to receiving the first dose of study medication.
* Has history of documented peptic ulcer disease (via endoscopy or x-ray), active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, 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 ZOFRAN, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
* Has previously received an NK-1 receptor antagonist.
* An active systemic infection or any uncontrolled disease (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 or planning to receive a systemic corticosteroid therapy at any dose within 72 hours prior to the first dose of study medication, except where indicated as premedication for a taxane. However, topical steroids and inhaled corticosteroids with a steroid dose of≤10 mg prednisone daily or its equivalent are permitted.
* Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this course of cisplatin therapy.
* Has received an investigational drug within the 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication, and/or is scheduled to receive any investigational drug during the study.
* Has received moderately and/or highly emetogenic medication within the 48 hours prior to the first dose of study medication. (Opioid narcotics for cancer pain will be permitted if the subject has been on such medication for at least 7 days and has not experienced nausea or emesis from the narcotics.)
* Has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drug. This includes, but is not limited to:

  * 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonestron is not permitted within 7 days prior to administration of 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 seven days prior to the first dose of GW679769 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)
  * butyrophenone (e.g., haloperidol, droperidol)
  * corticosteroids (e.g., dexamethasone, methylprednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders, and prophylactic treatment for taxane or pemetrexed therapy)
  * anticholinergics (e.g., scopolamine with the exception of inhaled anticholingerics for respiratory disorders e.g., ipratropium bromide)
  * antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine), except for prophylactic use for taxane therapy
  * domperidone
  * mirtazapine
  * olanzapine
  * cannabinoids
* Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 prior to administration of casopitant (GW679769) investigational product
* Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen days prior to the administration of casopitant investigational product
* Is taking the anti-diabetic agent repaglinide or the diuretic torsemide. Investigators are advised to exercise caution if including patients taking the anti-diabetic agents rosiglitazone or pioglitazone, or antimalarial agents such as chloroquine and amodiaquine, as the metabolite of casopitant is a potential inhibitor of CYP2C8
* Is currently taking or plans to take any of the following CYP3A4 substrates: astemizole, cisapride, pimozide, terfenadine.
C: Inclusion Criteria:

Cycle 1:

* Patient is scheduled to receive his/her first course of cisplatin chemotherapy at a dose of at least 70 mg/m\^2 administered a maximum of 3 hours
* Patient has a predicted life expectancy of at least 3 months
* Patient is not pregnant

Cycle 2 (optional):

* Participation in the study during the next cycle of chemotherapy is considered

appropriate by the investigator and will not pose unwarranted risk to the patient.

* Satisfactory completion of the preceding cycle of chemotherapy and related

study procedures.

* Patient will continue to receive the same chemotherapy regimen as in Cycle 1. The cisplatin dose may be reduced in subsequent cycle, as long as the new

dose is still no less than 70 mg/m\^2.

Exclusion Criteria:

Cycles 1 \& 2:

* Patient will receive stem cell therapy in conjunction with cisplatin
* Patient has an active infection or any uncontrolled disease (e.g. diabetes)
* Patient will receive multiple-day chemotherapy with cisplatin
* Patient will receive chemotherapy of moderate or high emetogenicity on the 6 days prior to cisplatin infusion or the 6 days following the cisplatin infusion
* Patient has vomited within 24 hours prior to cisplatin infusion
* Patient received or will receive radiation therapy to the abdomen
D: Inclusion Criteria:

* Patient is greater than 18 years of age.
* Patient is scheduled to receive his/her first

course of cisplatin chemotherapy for a solid tumor.

* Patient has a prognosis (life expectancy) greater than or equal to 3 months.

Answer: D