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

NCT00891761 | Withdrawn Phase 3

• 1 other identifier: 112512
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 3

Brief Summary

This is a phase III study designed to demonstrate the superiority of single-dose 90 mg intravenous (IV) casopitant over placebo, each in combination with ondansetron and dexamethasone, for the prevention of emesis over the first 0-120 hours (overall phase) following initiation of the cisplatin infusion in the first cycle of highly emetogenic chemotherapy (HEC). Eligibility is limited to subjects who are scheduled to receive their first cycle of chemotherapy which includes at least 60 mg/m2 of cisplatin administered on Day 1 only of a 21 day or 28 day cycle. All subjects will receive IV ondansetron and oral dexamethasone on Day 1 prior to initiation of the cisplatin infusion, followed by oral dexamethasone on Days 2-4. Additionally, subjects will be randomized to receive single-dose 90 mg IV casopitant or matching placebo prior to initiation of a cisplatin-based HEC regimen.

Conditions

Cancer; Chemotherapy-Induced Nausea and Vomiting; Nausea and Vomiting; Solid Tumor Cancer

Keywords

cisplatin; nausea; vomiting; cancer; lung cancer

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects who achieve a complete response (defined as no vomiting/retching and no rescue therapy).

  Overall phase (0-120 hours) following initiation of the first cycle of a cisplatin-based HEC regimen.

Secondary Outcomes (15)

• The proportion of subjects who vomit/retch

  Acute, delayed and overall phases of Cycle 1

• The proportion of subjects who receive anti-emetic rescue medication

  Acute, delayed and overall phases of Cycle 1

• Maximum nausea score (to assess the severity of nausea), assessed by a Visual Analogue Scale (VAS).

  Acute, delayed and overall phases of Cycle 1

• The proportion of subjects reporting significant nausea, defined as a maximum nausea score of at least 25 mm on the VAS.

  Acute, delayed and overall phases of Cycle 1

• The proportion of subjects who achieve a complete response

  Acute (0-24 hrs) and delayed (24-120 hrs) phases of Cycle 1

Study Arms (2)

Active Comparator

ACTIVE COMPARATOR

Patients receive IV casopitant (active), IV ondansetron and oral dexamethasone on Day 1 as well as oral dexamethasone on Days 2-4 of each cycle of cisplatin-based highly emetogenic chemotherapy for the prevention of chemotherapy induced nausea and vomiting.

Drug: Dexamethasone; Drug: IV casopitant (active); Drug: Ondansetron

Placebo Comparator

PLACEBO COMPARATOR

Patients receive IV casopitant (placebo), IV ondansetron and oral dexamethasone on Day 1 as well as oral dexamethasone on Days 2-4 of each cycle of cisplatin-based highly emetogenic chemotherapy for the prevention of chemotherapy induced nausea and vomiting.

Drug: Dexamethasone; Drug: IV casopitant (placebo); Drug: Ondansetron

Interventions

Dexamethasone DRUG

16 mg administered orally within 75 minutes prior to the initiation of cisplatin on Day 1, followed by 8 mg doses twice daily (bid) at approximately 12+/-4 hour intervals on days 2, 3, and 4, starting at approximately the same time of day as the Day 1 dose was administered.

Active Comparator

IV casopitant (placebo) DRUG

IV casopitant (placebo) administered within 75 minutes prior to the start of cisplatin-based highly emetogenic chemotherapy on study day 1.

Placebo Comparator

IV casopitant (active) DRUG

Single-dose 90 mg IV casopitant administered within 75 minutes prior to the start of cisplatin-based highly emetogenic chemotherapy on study Day 1.

Active Comparator

Ondansetron DRUG

32mg IV ondansetron administered over not less than 15 minutes, with administration started and completed within the 75 minutes prior to the initiation of cisplatin therapy on study Day 1.

Active Comparator; Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. Refer to Section 4.1 for the list of chemotherapy agents that may be added to oxaliplatin.
• 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 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.

You may not qualify if:

• 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.
• 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:
• 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);

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Tampa, Florida, 33614, United States

Location

GSK Investigational Site

Robbinsdale, Minnesota, 55422, United States

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Neoplasms; Vomiting; Nausea; Lung Neoplasms

Interventions

Dexamethasone; casopitant; Exercise; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 1, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: April 17, 2015

Record last verified: 2015-04

Locations

US (2); CA (1)