Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Study of the Efficacy and Safety of Oral Netupitant Administered in Combination With Palonosetron and Dexamethasone Compared to Oral Palonosetron and Dexamethasone for the Prevention of Nausea and Vomiting in Cancer Patients Receiving Moderately Emetogenic Chemotherapy
Brief Summary: NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. The objective of the study is to demonstrate that netupitant and palonosetron are more effective than palonosetron alone, to prevent nausea and vomiting induced by moderately emetogenic cancer chemotherapy after administration of repeated cycles of chemotherapy.


Options:
A: Inclusion Criteria:

* Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
* Scheduled to receive first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy (MEC) regimen for the treatment of a solid malignant tumor: 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).
* If scheduled to receive chemotherapy agents of minimal to low emetogenic potential they could be given on any day.
* Eastern Cooperative Oncology Group (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)

The following inclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:

* Participation in the study during the next cycle of chemotherapy is considered appropriate by the investigator Satisfactory study compliance in the preceding cycle of chemotherapy and related study procedures.
* Scheduled to receive the same chemotherapy regimen as cycle 1
* Adequate hematologic and metabolic status as defined for cycle 1

Exclusion Criteria:

* If female, pregnant or lactating.
* Current use of illicit drugs or current evidence of alcohol abuse.
* Scheduled to receive any highly emetogenic chemotherapy (HEC) from Day 1 to Day 5 or moderately emetogenic chemotherapy (MEC) from Day 2 to Day 5 following the allowed MEC regimen.
* Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to Day 1 or between Days 1 to 5 in cycle 1.
* Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.
* Symptomatic primary or metastatic central nervous system (CNS) malignancy.
* Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any uncontrolled medical condition (other than malignancy) that, in the opinion of the investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting, CINV) or pose unwarranted risks in administering the study drugs to the patient.
* Known hypersensitivity or contraindication to 5-HT3 receptor antagonists or dexamethasone.
* Previously received a neurokin-1 (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.
* Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
* Any medication with known or potential antiemetic activity within 24 hours prior to Day 1 of cycle 1
* Scheduled to receive any strong or moderate inhibitor of cytocrome P450 3A4 (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, including myocardial infarction within 3 months prior to Day 1, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, 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 such as systemic fungal infection or uncontrolled diabetes.

The following exclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:

* If female, pregnant or lactating
* Active infection or uncontrolled disease except for malignancy.
* Started any of the restricted medications.
* Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.
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:

* 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.
D: Inclusion Criteria:

1. Patients diagnosed as malignancy who will be treated with highly emetogenic chemotherapeutic agents (NCCN guideline v1.0 2011 anti-emesis), over 20 years and both sex
2. ECOG performance status 0-2
3. Available oral administration of study drugs
4. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion Criteria:

1. Severe Hypertension, severe Heart disease, kidney disease (serum creatinine \> 3 mg/dl), liver disease (AST, ALT \> 3 times of upper normal range, ALP \> 2 times of upper normal range)
2. Patients with GI obstruction, active gastric ulcer or other diseases that could provoke nausea and vomiting
3. Patients who have nausea and vomiting within 1 week before chemotherapy
4. Patients who should take steroid, antiemetics, pimozide, terfenadine, astemizole, cisapride, rifampin, carbamazepine, phenytoin, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir or nelfinavir for the treatment of other diseases
5. Patients with brain tumor, brain metastasis or seizure
6. Patients receiving chemotherapy within 12 months before enrollment
7. Patients who need radiation therapy during study period or receiving radiation therapy within 2 weeks before chemotherapy
8. Patients who have known allergy or severe side effect on study drugs
9. Pregnant or lactating women, or women who wish to become pregnant
10. Others whom the investigator judges inappropriate as subjects for this study

Answer: A