The Effects Of GW679769 (Casopitant) On The Pharmacokinetics Of Docetaxel In Subjects With Cancer

NCT00440128 | Completed Phase 1

• 1 other identifier: NKV100781
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of the study is to evaluate the effect of the study drug (GW679769) on a commonly used chemotherapy drug (docetaxel) which will be given I.V. Blood samples will be taken to see if the GW679769 alters the blood levels of the chemotherapy. The study will last about 2 weeks with a final follow-up visit 6 weeks later.

Conditions

Nausea and Vomiting, Chemotherapy-Induced

Keywords

Casopitant,; Neurokinin-1 Receptor Antagonist,; Drug-Interaction,; CYP3A; NK-1 Receptor Antagonist,; GW679769,; Docetaxel,

Outcome Measures

Primary Outcomes (1)

• Plasma levels of study drugs will be taken on Day 1 & 8.

  Plasma samples of study drugs

  taken on Day 1 & 8.

Secondary Outcomes (7)

• Safety is evaluated by: -AEs monitored at each visit

  starting at Day 1.

• -Physical exam, vital signs, & ECOG performance status score

  at Screening, Day 1,8,&15.

• -ECG

  at Screening & Day 15.

• -Serum Pepsinogen levels monitored

  at Screening & Followup

• Terminal half-life (t1/2, as data permit), AUC(0-t), volume of distribution at steady state (Vdss), and clearance (Cl) of docetaxel

  on Day 1 and 8.

Study Arms (2)

Docetaxel

ACTIVE COMPARATOR

Docetaxel

Drug: Docetaxel

Docetaxel/Casopitant

EXPERIMENTAL

Docetaxel/Casopitant

Drug: Casopitant/Docetaxel

Interventions

Docetaxel DRUG

Docetaxel

Docetaxel

Casopitant/Docetaxel DRUG

Casopitant/Docetaxel

Also known as: Docetaxel, Casopitant

Docetaxel/Casopitant

Eligibility Criteria

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

You may qualify if:

• Male or female
• years of age
• A female is eligible to enter and participate in this study if she is of:
• Non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had at least one of the following:
• Has had a hysterectomy, or
• Has had a bilateral oophorectomy (ovariectomy), or
• Has had a bilateral tubal ligation, or • Is considered post-menopausal (defined as amenorrheic for ≥ 1 year) and having serum follicle stimulating hormone (FSH) and serum estradiol concentrations consistent with post-menopausal status.
• Childbearing potential, has a negative serum pregnancy or negative urine pregnancy test within 24 hours prior to administration of the first dose of study medication and agrees to one of the following:
• Complete abstinence from sexual intercourse from two weeks prior to administration of the first dose of investigational product until 30 days after the final dose of study medication.
• Use double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm) from two weeks prior to administration of the first dose of investigational product until 30 days after the final dose of study medication.
• Vasectomized partner who has been documented to be sterile prior to the female subject's entry and is the sole sexual partner for that female.
• NOTE: if women of childbearing potential are enrolled, they must use double-barrier contraception in addition to oral contraceptives during the active study treatment period until 6 weeks after the final dose of study medication.
• Histologically confirmed malignant solid tumor and is scheduled to receive at least 2 courses of chemotherapy with docetaxel as a single intravenous dose of 20 to 40 mg/m2 given over a duration of one hour and repeated weekly.
• Received eight or fewer previous doses of docetaxel. Subjects that have received more than eight doses of docetaxel must receive permission from the GSK medical monitor in order to be eligible for the study.
• ECOG performance status score of less than or equal to 2

You may not qualify if:

• Pregnant or lactating.
• Received radiation therapy to the abdomen or the pelvis in the 28 days prior to receiving the first dose of study medication or that are scheduled to receive radiation therapy to the abdomen or the pelvis in the six days following the first dose of study medication.
• Received a dose of docetaxel during the week prior to Day -1.
• Known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been stable for at least 3 months prior to receiving the first dose of study medication.
• Active systemic infection or any poorly controlled medical condition (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 regular treatment with high dose systemic corticosteroid therapy or steroid dose within 72 hours prior to receiving the first dose of study medication. Topical steroids and inhaled corticosteroids with a steroid dose of less than or equal to 10 mg prednisone daily (or its equivalent) are permitted if the subject has been on this dose for at least 14 days prior to dosing.
• Hypersensitivity or contraindication to ondansetron or other 5-HT3 receptor antagonist, dexamethasone, docetaxel, casopitant, or any component of the above mentioned medications.
• Received an investigational drug within the 28 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication, or is scheduled to receive any investigational drug during the study.
• Use of strong inhibitors of CYP3A4 or CYP3A5 prior to the first dose of study medication
• Use of drugs with a narrow therapeutic index that interact with the P-glycoprotein pathway within 14 days prior to the first dose of study medication until 14 days after the last dose of docetaxel including digoxin.
• Use of drugs with a narrow therapeutic index that are metabolized by CYP2C8 within 14 days prior to the first dose of study medication including repaglinide and torsemide.
• Disease that will significantly affect absorption of oral medications.
• Inadequate venous access for pharmacokinetic sampling.
• Unresolved Grade 2 or worse toxicity from prior therapy.
• Active peptic ulcer disease (PUD) or a history of PUD of unknown etiology. NOTE: Subject is eligible to enter and participate in this study if they have a history of PUD of known etiology with documentation from a gastroenterologist or other qualified physician of the etiology of the PUD and that effective treatment was provided with full eradication of ulcers and symptoms. Subjects who present with symptoms of gastroesophageal reflux disease (GERD) are eligible. However, if the investigator suspects PUD in such a subject, the subject must have a GI assessment to rule out PUD. If assessment is negative, subject may enter the study. For these subjects, appropriate steps must also have been taken to minimize the risk of reoccurrence. If PUD was non-steroidal anti-inflammatory drug (NSAID) induced, the subject should no longer be taking NSAID medication(s). If PUD was induced by H. pylori, the subject should have been appropriately treated.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Hot Springs, Arkansas, 71913, United States

Location

GSK Investigational Site

Iowa City, Iowa, 52242, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (1)

• Dandamudi UB, Adams LM, Johnson B, Bauman J, Morris S, Murray S, Webb RT, Gartner E, Hohl R, Lewis LD. Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer. Cancer Chemother Pharmacol. 2011 Apr;67(4):783-90. doi: 10.1007/s00280-010-1381-2. Epub 2010 Jun 17.

  PMID: 20556613 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study NKV100781 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Nausea; Vomiting

Interventions

Docetaxel; casopitant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2007
• First Posted: February 26, 2007
• Study Start: May 4, 2007
• Primary Completion: July 17, 2008
• Study Completion: July 17, 2008
• Last Updated: August 4, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (4)