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

A Phase I, Open-Label, Randomized, Two Period Crossover Study to Investigate the Effects of GW679769 on the Pharmacokinetics of Docetaxel in Subjects With Cancer

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.

Study Overview

• Status: Completed
• Conditions: Nausea and Vomiting, Chemotherapy-Induced
• Intervention / Treatment: Drug: Docetaxel; Drug: Casopitant/Docetaxel

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • GSK Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • GSK Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female
• 18 years of age

• A female is eligible to enter and participate in this study if she is of:

  1. 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.

  2. 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

NOTE: If the subject's performance status deteriorates between the screening Visit and the time of first dose of study drug to a score > 2, the subject will be excluded from the study

• Adequate hematologic and other physiological organ function as evidenced by Absolute Neutrophil Count ≥1500/mm3. Platelets ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL Serum creatinine < 1.5 mg/dL Total Bilirubin ≤ upper limit of the reference range Aspartate Transaminase (AST) < 2 x upper limit of the reference range Alanine Transaminase (ALT) < 2 x upper limit of the reference range Alkaline Phosphatase < 2.5 x upper limit of the reference range. Calculated creatinine clearance > 50 mL/min (measured by Cockcroft Gault Formula;)
• Written informed consent is obtained prior to any study-specific procedures or assessments.
• Able to swallow and retain oral medications.

Exclusion Criteria:

• 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 inducers of CYP3A4 or CYP3A5 (other than steroids described in Exclusion Criteria 5) within 14 days 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.
• Stool positive for occult blood. Test may be repeated once if subject did not abstain from red meat for the previous three days.
• Pepsinogen level below the lower limit of laboratory reference range (LLRR).
• Troponin level above 10% of the coefficient of variation of the assay as determined by the laboratory performing the test.
• Calculated QT interval (QTc) > 480 msecs.
• Clinically significant cardiac disease that would interfere with participation in the study as determined by the investigator.
• Known or suspected iron deficiency.
• Use of NSAIDS, including aspirin at any dose, and including COX2 inhibitors. These medications are prohibited 7 days prior to administration of study drug and for the duration of the study until 72 hours after the last dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Docetaxel	Drug: Docetaxel; Docetaxel
Experimental: Docetaxel/Casopitant	Drug: Casopitant/Docetaxel; Casopitant/Docetaxel; Other Names: Docetaxel; Casopitant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of study drugs will be taken on Day 1 & 8.	Plasma samples of study drugs	taken on Day 1 & 8.

Secondary Outcome Measures

Outcome Measure	Time Frame
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.
Lowest measured absolute neutrophil count.	on Day 1 and 8
Physical exam findings, blood pressure, heart rate, clinical laboratory tests, clinical monitoring/observation, and adverse events reporting.	on Day 1 and 8

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2007
• Primary Completion (Actual): July 17, 2008
• Study Completion (Actual): July 17, 2008

Study Registration Dates

• First Submitted: February 22, 2007
• First Submitted That Met QC Criteria: February 22, 2007
• First Posted (Estimate): February 26, 2007

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: GW679769,; CYP3A; Casopitant,; Neurokinin-1 Receptor Antagonist,; Drug-Interaction,; NK-1 Receptor Antagonist,; Docetaxel,
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Docetaxel; Casopitant
• Other Study ID Numbers: NKV100781

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: NKV100781
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register