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

NCT00431236 | Completed Phase 3

• 1 other identifier: NKV102551
• Study Type: interventional
• Target: 810
• Locations: 22 countries
• Sites: 80

Brief Summary

This is a Phase III trial designed to demonstrate that casopitant when added to dexamethasone and ondansetron is more effective in the prevention of vomiting then dexamethasone and ondansetron alone, in patients who receive a cisplatin-based highly emetogenic chemotherapy.

Conditions

Nausea and Vomiting, Chemotherapy-Induced

Keywords

cisplatin; CINV; highly emetogenic

Outcome Measures

Primary Outcomes (1)

• Number of participants who achieved complete response

  Complete response was defined as no vomiting/retching and no rescue therapy) over the first 120 hours following the initiation of their first cycle of a cisplatin-based HEC regimen. Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that was not productive of gastrointestinal contents (also known as "dry heaves").

  Up to 120 hours of cycle 1 of HEC

Secondary Outcomes (22)

• 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

  Up to 120 hours of cycle 1 of HEC

• Number of participants who achieved a complete response during the overall (0-120 hours) phase following subsequent cycles of HEC

  Up to 120 hours of cycle of HEC 2 to 6

• Maximum nausea score (to assess the severity of nausea), as assessed by a visual analogue scale (VAS)

  Up to 120 hours of each HEC cycle (up to 24 months)

• Number of participants who use of anti-emetic rescue medication

  Up to 120 hours of each HEC cycle (up to 24 months)

• Number of participants with first emetic event

  Up to 120 hours of each HEC cycle (up to 24 months)

Interventions

Oral Casopitant (GW679769) DRUG

IV Casopitant (GW679769) DRUG

IV ondansetron hydrochloride DRUG

Oral dexamethasone DRUG

Also known as: IV ondansetron hydrochloride, IV Casopitant (GW679769), Oral Casopitant (GW679769)

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.
• 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.

You may not qualify if:

• 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 steroids and inhaled corticosteroids with a steroid dose of≤10 mg prednisone daily or its equivalent are permitted.
• Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this course of cisplatin therapy.
• Has received an investigational drug within the 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication, and/or is scheduled to receive any investigational drug during the study.
• Has received moderately and/or highly emetogenic medication within the 48 hours prior to the first dose of study medication. (Opioid narcotics for cancer pain will be permitted if the subject has been on such medication for at least 7 days and has not experienced nausea or emesis from the narcotics.)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (80)

GSK Investigational Site

Capital Federal, Buenos Aires, C1405CUB, Argentina

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GSK Investigational Site

Córdoba, Córdoba Province, X5000JFK, Argentina

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GSK Investigational Site

Rosario, Santa Fe Province, S2000KZE, Argentina

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GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

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GSK Investigational Site

Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Sofia, 1756, Bulgaria

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Varna, 9010, Bulgaria

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Zagreb, 10 000, Croatia

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Zagreb, 10000, Croatia

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GSK Investigational Site

Zagreb, Croatia

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GSK Investigational Site

Brno, 625 00, Czechia

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GSK Investigational Site

Brno, 65691, Czechia

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GSK Investigational Site

Jihlava, 586 01, Czechia

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GSK Investigational Site

Ostrava, 708 52, Czechia

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Prague, 150 06, Czechia

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GSK Investigational Site

Tábor, 390 19, Czechia

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GSK Investigational Site

Helsinki, 00029, Finland

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GSK Investigational Site

Kangasala, 36280, Finland

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Turku, 20520, Finland

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GSK Investigational Site

Athens, 13122, Greece

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GSK Investigational Site

Kavala, 65403, Greece

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GSK Investigational Site

Papagos, Athens, 15669, Greece

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Thessaloniki, 564 29, Greece

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GSK Investigational Site

Thessaloniki, 57010, Greece

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GSK Investigational Site

Budapest, 1529, Hungary

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GSK Investigational Site

Mátraháza, 3233, Hungary

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GSK Investigational Site

Székesfehérvár, 8000, Hungary

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GSK Investigational Site

Kochi, 682026, India

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GSK Investigational Site

Tirupati, 517507, India

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Dublin, 9, Ireland

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Tallaght, Dublin, 24, Ireland

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GSK Investigational Site

Wilton, Cork, Ireland

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GSK Investigational Site

Monteforte Irpino, Campania, 83024, Italy

Location

GSK Investigational Site

Rome, Lazio, 00149, Italy

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GSK Investigational Site

Rome, Lazio, 00184, Italy

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GSK Investigational Site

Sassari, Sardinia, 07100, Italy

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GSK Investigational Site

Pisa, Tuscany, 56124, Italy

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GSK Investigational Site

George Town, 11600, Malaysia

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GSK Investigational Site

Kubang Kerian, 16150, Malaysia

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Sarawak, 93586, Malaysia

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GSK Investigational Site

Islamabad, 1590, Pakistan

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Karachi, 54000, Pakistan

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GSK Investigational Site

Karachi, 74800, Pakistan

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Lahore, 53400, Pakistan

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GSK Investigational Site

Lahore, 54600, Pakistan

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GSK Investigational Site

Baguio City, Benguet, 2600, Philippines

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GSK Investigational Site

Manila, 1000, Philippines

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GSK Investigational Site

Quezon City, 1100, Philippines

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GSK Investigational Site

Bialystok, 15-540, Poland

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GSK Investigational Site

Bydgoszcz, 85-796, Poland

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GSK Investigational Site

Krakow, 31-115, Poland

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GSK Investigational Site

Olsztyn, 10-357, Poland

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GSK Investigational Site

Poznan, 60-569, Poland

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GSK Investigational Site

Poznan, 61-866, Poland

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GSK Investigational Site

Bucharest, 022328, Romania

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GSK Investigational Site

Iași, 700106, Romania

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GSK Investigational Site

Timișoara, 300239, Romania

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GSK Investigational Site

Banská Bystrica, 975 17, Slovakia

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GSK Investigational Site

Bratislava, 826 06, Slovakia

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GSK Investigational Site

Poprad, 058 87, Slovakia

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GSK Investigational Site

Seoul, 120-752, South Korea

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GSK Investigational Site

Seoul, 135-710, South Korea

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GSK Investigational Site

Seoul, 138-736, South Korea

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GSK Investigational Site

Ávila, 05071, Spain

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Madrid, 28035, Spain

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GSK Investigational Site

Murcia, 30008, Spain

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GSK Investigational Site

Valencia, 46009, Spain

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GSK Investigational Site

Taichung, 404, Taiwan

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GSK Investigational Site

Taichung, 40705, Taiwan

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GSK Investigational Site

TaoYuan Hsien, 333, Taiwan

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GSK Investigational Site

Bangkok, 10400, Thailand

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GSK Investigational Site

Chiang Mai, 50200, Thailand

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GSK Investigational Site

Kharkiv, 61024, Ukraine

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GSK Investigational Site

Kyiv, 03115, Ukraine

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GSK Investigational Site

Lviv, 79031, Ukraine

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GSK Investigational Site

Sympheropol, 95023, Ukraine

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GSK Investigational Site

Uzhhorod, 88014, Ukraine

Location

Related Publications (1)

• Grunberg SM, Rolski J, Strausz J, Aziz Z, Lane S, Russo MW, Wissel P, Guckert M, Wright O, Herrstedt J. Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jun;10(6):549-58. doi: 10.1016/S1470-2045(09)70109-3. Epub 2009 May 8.

  PMID: 19428297 RESULT

MeSH Terms

Conditions

Nausea; Vomiting

Interventions

casopitant; Ondansetron; Dexamethasone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2007
• First Posted: February 5, 2007
• Study Start: November 6, 2006
• Primary Completion: October 9, 2007
• Study Completion: October 9, 2007
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

SL (3); KR (3); ES (5); GR (5); HU (3); IT (5); PL (6); TW (3); RO (3); TH (2); FI (3); UA (5); BE (3); CR (3); PA (5); PH (3); IE (3); BU (2); AR (4); CZ (6); MY (3); IN (2)