A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Oxaliplatin Induced Nausea and Vomiting.
- 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
- 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
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
- double-barrier method of contraception consisting of spermicide with either condom or
- 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.
- 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
- 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
- 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
- first-generation antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine;
see Appendix 4); except for topical use which is permitted;
- 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.