A Study of the Drug Casopitant for the Prevention of Nausea Caused By Cisplatin-Based Highly Emetogenic Chemotherapy

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00431236
• Date of registration: 02/02/2007
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: A Study of the Drug Casopitant for the Prevention of Nausea Caused By Cisplatin-Based Highly Emetogenic Chemotherapy
• Scientific title: A Phase III Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group Study of the Efficacy and Safety of the Intravenous and Oral Formulations of the Neurokinin-1 Receptor Antagonist, Casopitant, Administered in Combination With ZOFRAN and Dexamethasone for Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Subjects Receiving Highly Emetogenic Cisplatin-Based Chemotherapy
• Date of first enrolment: November 6, 2006
• Target sample size: 810
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00431236
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention.
• Phase: Phase 3

Countries of recruitment

Argentina, Belgium, Bulgaria, Croatia, Czech Republic, Czechia, Finland, Greece, Hungary, India, Ireland, Italy, Korea, Republic of, Malaysia, Pakistan, Peru, Philippines, Poland, Romania, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Nausea and Vomiting, Chemotherapy-Induced

Intervention(s)

Drug: Oral dexamethasone

Drug: IV ondansetron hydrochloride

Drug: IV Casopitant (GW679769)

Drug: Oral Casopitant (GW679769)

Primary Outcome(s)

Number of participants who achieved complete response [Time Frame: Up to 120 hours of cycle 1 of HEC]

Secondary Outcome(s)

Number of participants who use of anti-emetic rescue medication [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Number of participants with adverse events (AE) and serious adverse events (SAE) [Time Frame: Up to 24 month after last dose of investigational product]

Percentage of participants with impact on daily life activities for the first 120 hours following the first cycle of chemotherapy as assessed by the FLIE questionnaire-interpretation [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Number of participants who received anti-emetic rescue medication [Time Frame: Up to 120 hours of cycle 1 of HEC]

Number of participants who reported significant nausea (>=25 mm on the VAS) [Time Frame: Up to 120 hours of cycle 1 of HEC]

Number of participants with first emetic event [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Number of participants who achieved a complete response during the overall (0-120 hours) phase following subsequent cycles of HEC [Time Frame: Up to 120 hours of cycle of HEC 2 to 6]

Number of participants who achieved complete response during the acute (0-24 hours) and the delayed (24-120 hours) phase following the first cycle of HEC [Time Frame: Up to 120 hours of cycle 1 of HEC]

Number of participants with nausea as assessed by a categorical scale, over the first 120 hours following HEC [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Summary of mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) [Time Frame: Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months]

Number of participants who vomited/retched [Time Frame: Up to 120 hours of cycle 1 of HEC]

Number of participants who achieved complete protection, defined as no vomiting/retching, no significant nausea and no rescue medication [Time Frame: Up to 120 hours of cycle 1 of HEC]

Number of participants with abnormalities of Grade 3 and 4 in laboratory parameters (clinical chemistry and hematology) [Time Frame: Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months]

Participant satisfaction with the prophylactic anti-emetic regimens, as assessed by the participant satisfaction questionnaire [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Summary of mean respiratory rate [Time Frame: Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months]

Maximum nausea score (to assess the severity of nausea), as assessed by a visual analogue scale (VAS) [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Number of participants who achieved total control, defined as no vomiting/retching, no nausea and no rescue medication [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Number of participants who reported nausea (>=5 mm on the VAS) [Time Frame: Up to 120 hours of cycle 1 of HEC]

Summary of abnormal electrocardiogram findings [Time Frame: Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months]

Summary of mean heart rate [Time Frame: Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months]

The impact on participants daily life activities for the first 120 hours following the first cycle of chemotherapy as assessed by the Functional Living Index-Emesis (FLIE) questionnaire-Score [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

The willingness of participant to use the same treatment during future chemotherapy, as assessed by the participant willingness questionnaire [Time Frame: Up to 120 hours of each HEC cycle (up to 24 months)]

Secondary ID(s)

NKV102551

Source(s) of Monetary Support

Please refer to primary and secondary sponsors