Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3, Multicenter, Randomized, Double Blind, Active-Controlled Study of the Safety & Efficacy of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)
Brief Summary: This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving HEC. Rolapitant or placebo will be administered prior to initiation of chemotherapy on Day 1 with granisetron and dexamethasone. Subjects will record all events of emesis and use of rescue medication for established nausea and/or vomiting, and will indicate the severity of nausea they experienced in each of the previous 24 hours in the Nausea and Vomiting (NV) Subject Diary prior to HEC administration through Day 6 of Cycle 1. Health-related quality of life will be measured by the FLIE Questionnaire on Day 6 of Cycle 1. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.

All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles.


Options:
A: Inclusion Criteria:

* Subjects will be males or nonpregnant females who are 18-87 years of age at the time of enrollment.
* Subjects must have histologically or cytologically confirmed malignant disease.
* Subjects must be undergoing treatment with a HEC regimen according to the 2011 ASCO CINV guidelines for further details on the emetogenic classifications of chemotherapy agents for this study).
* A life expectancy \> 6 months
* Subjects must be able to receive standardized doses of dexamethasone as required in the protocol for the prevention of emesis.
* Subjects must be characterized as having Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Subjects must have adequate bone marrow, kidney, and liver function.
* Subjects must be able to swallow oral medications (pills) without difficulty.
* Subjects must be entering the first cycle of their current chemotherapy regimen.
* Subjects must be willing and able to comply with all testing and requirements defined in the protocol.
* Subjects must be able to provide voluntary, written, informed consent to participate in this study and must be able to fully understand the study requirements.
* Female subjects cannot be pregnant and must be adequately protected from conception for the duration of study, using at least one form of contraception. It is recommended that females and female partners of male subjects remain adequately protected from conception during the study and for up to 1 year following study participation.

Exclusion Criteria:

* Subject has a known hypersensitivity to granisetron or any 5-HT3 receptor antagonist.
* Subject has a history or presence of clinically significant abnormal 12-lead ECG or an ECG with QTc by Bazett's correction of \> 450 msec in men and \> 470 msec in women on the screening ECG.
* Subject has PR \> 240 msec, QRS \> 110 msec, or a history of prolongation of QT interval.
* Subject has a family history of long QT syndrome.
* Subject has a history of cardiac disease, including congenital long QT syndrome, angina, myocardial ischemia or infarction, congestive heart failure, myocarditis, or chest pain or dyspnea on exertion.
* Subject has an electrolyte disturbance, such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, or hypocalcemia.
* Subject has idiopathic cardiomyopathy, syncope, epilepsy, hypertrophic cardiomyopathy, or other clinically significant cardiac disease.
* Subject is pregnant or breast-feeding.
* Subject is planning to receive multiple-day chemotherapy.
* Subject has taken any of the following agents within 7 days prior to initiation of chemotherapy (the study): 5-HT3 receptor antagonists, phenothiazines, benzamides, domperidone, cannabinoids, or NK-1 receptor antagonist.
* Subject has taken any benzodiazepine within 1 day (24 hours) prior to initiation of chemotherapy (the study).
* Subject is scheduled to receive any other chemotherapeutic agent from Day 2 through Day 6.
* Subject is scheduled to receive any radiation therapy to the abdomen or pelvis from Day -5 through Day 6.
* Subject has received systemic corticosteroids or sedative antihistamines within 72 hours of Day 1 of the study, except as premedication for chemotherapy (e.g., taxanes, pemetrexed).
* Subject has symptomatic primary or metastatic central nervous system (CNS) disease.
* Subject has ongoing vomiting, retching, or nausea caused by any etiology, or has a history of anticipatory nausea and vomiting.
* Subject has vomited and/or has had dry heaves or retching within 24 hours prior to the start of HEC on Day 1.
* Subject is NOT able to swallow oral medications (pills) without difficulty.
B: 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.
C: Inclusion Criteria:

* 18 years of age or older, of either gender, and of any race
* has never been treated with cisplatin and is to receive the first course of cisplatin-based chemotherapy (≥60 mg/m2)
* Karnofsky performance score of ≥60
* Predicted life expectancy of ≥4 months
* Adequate bone marrow, kidney, and liver function

Exclusion Criteria:

* Contraindication to cisplatin, granisetron, or dexamethasone
* Is pregnant or breast feeding
* Has previously received cisplatin or subject is planning to receive multiple days of cisplatin in a single cycle
* Has taken the following agents within the last 48 hours 5-HT3 antagonists,Phenothiazines,Benzamides,Domperidone,Cannabinoids,NK1 antagonist, Benzodiazepines
* Scheduled to receive any other chemotherapeutic agent with an emetogenicity level of 4 or above (Hesketh Scale) from Day 2 through Day 6, except on Day 1.
* Scheduled to receive any radiation therapy to the abdomen or pelvis from Day -5 through Day 6
* Has received systemic corticosteroids or sedative antihistamines within 72 hours of Day 1 of the study except as premedication for chemotherapy (e.g., taxanes, pemetrexed)
* symptomatic primary or metastatic CNS disease.
* Has ongoing vomiting, retching, clinically significant nausea caused by any etiology, or has a history of anticipatory nausea and vomiting.
* Has vomited and/or has had dry heaves/retching within 24 hours prior to the start of cisplatin-based chemotherapy on Day 1 in Cycle 1.
D: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed malignant disease

  * No head and neck cancer or upper gastrointestinal cancer
* Scheduled to receive a single day of moderately or highly emetogenic chemotherapy regimen (for ≤ 4 courses)

  * Chemotherapy administration ≤ 4 hours
  * Duration of each course ≤ 28 days
  * Causing nausea and vomiting in 30-100% of patients if untreated according to Hesketh algorithm
* Must be able to receive standardized doses of dexamethasone for the prevention of emesis during study treatment
* No greater than mild nausea or any vomiting within 24 hours before beginning study treatment

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No known allergy or hypersensitivity to other selective 5-HT3 receptor antagonists or local anesthetics
* QTc interval ≤ 500 ms
* No cardiac abnormality predisposing the patient to arrhythmia
* No psychological problem that, in the opinion of the investigator, is severe enough to preclude study participation
* No recent history (i.e., ≤ 1 year) of alcohol or drug abuse
* No concurrent condition that, in the opinion of the investigator, could affect assessment of study medication or interfere with the nausea/vomiting response (e.g., severe renal or hepatic impairment)

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No radiotherapy 7 days prior to, during, and 5 days after completion of study treatment
* More than 7 days since prior chemotherapy
* More than 7 days since prior and no concurrent prohibited medications (e.g., CYP3A4 inhibitors or other antiemetic medications)
* More than 7 days since prior antinausea medications
* More than 30 days since prior treatment on an investigational trial
* No other concurrent corticosteroids or dexamethasone at a different dose than study treatment
* No concurrent use of APF530, palonosetron hydrochloride, or aprepitant as rescue medications

Answer: C