KV110721, A Study of Single Dose Intravenous Casopitant in Combination with Ondansetron and Dexamethasone for the Prevention of Oxaliplatin-Induced Nausea and Vomiting

Phase 1

Conditions: Prevention of nausea and vomiting due to first cycle of oxaliplatin based chemotherapy in patients with colorectal cancer receiving a combination with 5-fluorouracil and leucovorin, or in combination with capecitabine.

Registration Number: EUCTR2007-005169-36-SK

Lead Sponsor: GlaxoSmithKline Research and Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1. 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.
2. At least 18 years of age.
3. 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. Refer to Section 4.1 for the list of chemotherapy agents that may be added to oxaliplatin.
4. An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
5. 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 109/L)
• Platelets =100,000/mm3 (Standard units: =100.0 x 109/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.
6. Is willing and able to complete daily components of the Subject Diary for Cycle 1 and Cycle 2 without assistance from others.
7. A female subject is eligible to enter and participate in this study if she is of:
a. 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)
b. 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 spermic

Exclusion Criteria

1. 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.
2. Scheduled to receive chemotherapy with any cytotoxic agents or biological agents other than the protocol allowed chemotherapy described in Inclusion Criterion 3.
3. Is a female subject who is pregnant or lactating.
4. 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.
5. Has experienced emesis or clinically significant nausea in the 24 hours preceding the first dose of study medication or investigational product for each cycle of chemotherapy.
6. 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.
7. 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.
8. Has a known hypersensitivity or contraindication to ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
9. Has received an NK-1 receptor antagonist prior to the first study cycle of chemotherapy.
10. 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.
11. Has taken/received any medication of moderate or high emetogenic potential 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.
12. 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 mdication during the 120 hour assessment period for Cycle 1 of therapy only. This includes, but is not limited to:
• 5-HT3 receptor antagonists. Palonosetron is not permitted within 7 days prior to administration of study medication or investigational product;
• benzamide / benzamide derivatives;

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method