Fosaprepitant in Patients Receiving Ifosfamide-based Regimen - Full Text View

Purpose

The goal of this clinical research study is to learn how different doses of fosaprepitant may effect how ifosfamide-based chemotherapy is absorbed by the body. Researchers also want to learn if fosaprepitant can help to control or prevent delayed nausea and/or vomiting that may be caused by chemotherapy. The safety of this drug will also be studied.

Fosaprepitant is designed to block the natural substance in the brain that causes nausea and vomiting. This may help to prevent and/or control nausea and vomiting caused by chemotherapy.

Condition	Intervention
Sarcoma Chemotherapy-induced Nausea and Vomiting Effects of Chemotherapy Adverse Effects of Medical Drugs	Drug: Fosaprepitant Drug: Dexamethasone Drug: 5HT3 receptor antagonist Drug: Ifosfamide-based chemotherapy (AI) Drug: Doxorubicin Drug: Mesna Drug: Ifosfamide Drug: Vincristine

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Evaluation of Fosaprepitant's Effect on Drug Metabolism in Sarcoma Patients Receiving Ifosfamide-based Multi-day Chemotherapy Regimen

Resource links provided by NLM:

MedlinePlus related topics: Cancer Nausea and Vomiting Soft Tissue Sarcoma

Drug Information available for: Dexamethasone Serotonin Dexamethasone acetate Vincristine sulfate Dexamethasone sodium phosphate Ifosfamide Mesna Doxorubicin Doxorubicin hydrochloride Aprepitant Fosaprepitant Fosaprepitant dimeglumine

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Plasma Areas Under the Concentration Curve (AUC) of Ifosfamide [ Time Frame: From Day 1 to Day 4 in two 21-days cycles ] [ Designated as safety issue: No ]
Effect of Fosaprepitant on Ifosfamide metabolism by pharmacokinetics (PK), Day 1 and Day 4 plasma AUC0-24s (area under curve during 24 hours) of ifosfamide. PK measures (AUC) for ifosfamide calculated for participants that complete 2 cycles of chemotherapy and PK blood collection. PK sampling during first 2 chemotherapy cycles, prior to chemotherapy infusion (baseline) and post-infusion (3 hour from initiation of ifosfamide), and 4 , 6, 8, and 24 hour time points from the initiation of ifosfamide infusion on day 1 and day 4 (last infusion of ifosfamide) in first 2 cycles for all patients.

Estimated Enrollment:	40
Study Start Date:	May 2012
Estimated Primary Completion Date:	May 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single Dose Day 1 Arm 1, Single Dose: Fosaprepitant 150 mg intravenous (IV) Day 1 of Cycle 1 or Day 1 of Cycle 2. Participants randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2); or Group 2 (No Fosaprepitant Cycle 1 and Fosaprepitant Cycle 2). Dexamethasone intravenously (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy. Doxorubicin 25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy.	Drug: Fosaprepitant 150 mg administered intravenously, delivered in either single dose or two doses, on Day 1 for single dose and on Days 1 and 4 for two doses, varying between Cycle 1 or Cycle 2 depending upon randomization to arm. Other Name: Fosaprepitant Dimeglumine Drug: Dexamethasone Intravenous push (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) Other Names: Dexamethasone acetate Decadron Drug: 5HT3 receptor antagonist 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy Drug: Ifosfamide-based chemotherapy (AI) Doxorubicin + Mesna + + Ifosfamide + Vincristine, chemotherapy cycles repeated every 3-4 weeks for up to 6 cycles. Chemotherapy drugs listed separately, individual dosages, etc. Drug: Doxorubicin 25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy. Other Names: Rubex Adriamycin Adriamycin RDF Adriamycin PFS Doxorubicin Hydrochloride Drug: Mesna Prior to ifosfamide (Day 1) - 500 mg/m2 (20% of ifosfamide dose) given simultaneously with ifosfamide and then daily continuous infusion (Days 1-4 completing infusion on day 4) - 1,500 mg/m2/day (60% of daily ifosfamide dose) for a total of 6 gm/m2. The mesna infusion complete 24 hours after last dose of ifosfamide. Other Name: Mesnex Drug: Ifosfamide 2.5 g/m2 IV bolus over 3 hours on days 1, 2, 3, 4 (total dose: 10 g/m2). Other Name: Ifex Drug: Vincristine 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.
Experimental: Two Doses Day 1 + Day 4 Arm 2, Two Doses: Fosaprepitant 150 mg IV Day 1 + Day 4 of Cycle 1 or Day 1 + Day 4 of Cycle 2. Participants randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2); or Group 2 (No Fosaprepitant Cycle 1 and Fosaprepitant Cycle 2). Dexamethasone intravenously (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy. Doxorubicin 25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy.	Drug: Fosaprepitant 150 mg administered intravenously, delivered in either single dose or two doses, on Day 1 for single dose and on Days 1 and 4 for two doses, varying between Cycle 1 or Cycle 2 depending upon randomization to arm. Other Name: Fosaprepitant Dimeglumine Drug: Dexamethasone Intravenous push (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) Other Names: Dexamethasone acetate Decadron Drug: 5HT3 receptor antagonist 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy Drug: Ifosfamide-based chemotherapy (AI) Doxorubicin + Mesna + + Ifosfamide + Vincristine, chemotherapy cycles repeated every 3-4 weeks for up to 6 cycles. Chemotherapy drugs listed separately, individual dosages, etc. Drug: Doxorubicin 25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy. Other Names: Rubex Adriamycin Adriamycin RDF Adriamycin PFS Doxorubicin Hydrochloride Drug: Mesna Prior to ifosfamide (Day 1) - 500 mg/m2 (20% of ifosfamide dose) given simultaneously with ifosfamide and then daily continuous infusion (Days 1-4 completing infusion on day 4) - 1,500 mg/m2/day (60% of daily ifosfamide dose) for a total of 6 gm/m2. The mesna infusion complete 24 hours after last dose of ifosfamide. Other Name: Mesnex Drug: Ifosfamide 2.5 g/m2 IV bolus over 3 hours on days 1, 2, 3, 4 (total dose: 10 g/m2). Other Name: Ifex Drug: Vincristine 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Arms

Assigned Interventions

Experimental: Single Dose Day 1

Arm 1, Single Dose: Fosaprepitant 150 mg intravenous (IV) Day 1 of Cycle 1 or Day 1 of Cycle 2. Participants randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2); or Group 2 (No Fosaprepitant Cycle 1 and Fosaprepitant Cycle 2). Dexamethasone intravenously (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy. Doxorubicin 25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy.

Drug: Fosaprepitant

150 mg administered intravenously, delivered in either single dose or two doses, on Day 1 for single dose and on Days 1 and 4 for two doses, varying between Cycle 1 or Cycle 2 depending upon randomization to arm.

Other Name: Fosaprepitant Dimeglumine

Drug: Dexamethasone

Intravenous push (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5)

Other Names:

Dexamethasone acetate
Decadron

Drug: 5HT3 receptor antagonist

5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy

Drug: Ifosfamide-based chemotherapy (AI)

Doxorubicin + Mesna + + Ifosfamide + Vincristine, chemotherapy cycles repeated every 3-4 weeks for up to 6 cycles. Chemotherapy drugs listed separately, individual dosages, etc.

Drug: Doxorubicin

25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy.

Other Names:

Rubex
Adriamycin
Adriamycin RDF
Adriamycin PFS
Doxorubicin Hydrochloride

Drug: Mesna

Prior to ifosfamide (Day 1) - 500 mg/m2 (20% of ifosfamide dose) given simultaneously with ifosfamide and then daily continuous infusion (Days 1-4 completing infusion on day 4) - 1,500 mg/m2/day (60% of daily ifosfamide dose) for a total of 6 gm/m2. The mesna infusion complete 24 hours after last dose of ifosfamide.

Other Name: Mesnex

Drug: Ifosfamide

2.5 g/m2 IV bolus over 3 hours on days 1, 2, 3, 4 (total dose: 10 g/m2).

Other Name: Ifex

Drug: Vincristine

2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Experimental: Two Doses Day 1 + Day 4

Arm 2, Two Doses: Fosaprepitant 150 mg IV Day 1 + Day 4 of Cycle 1 or Day 1 + Day 4 of Cycle 2. Participants randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2); or Group 2 (No Fosaprepitant Cycle 1 and Fosaprepitant Cycle 2). Dexamethasone intravenously (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy. Doxorubicin 25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy.

Drug: Fosaprepitant

150 mg administered intravenously, delivered in either single dose or two doses, on Day 1 for single dose and on Days 1 and 4 for two doses, varying between Cycle 1 or Cycle 2 depending upon randomization to arm.

Other Name: Fosaprepitant Dimeglumine

Drug: Dexamethasone

Intravenous push (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5)

Other Names:

Dexamethasone acetate
Decadron

Drug: 5HT3 receptor antagonist

5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy

Drug: Ifosfamide-based chemotherapy (AI)

Doxorubicin + Mesna + + Ifosfamide + Vincristine, chemotherapy cycles repeated every 3-4 weeks for up to 6 cycles. Chemotherapy drugs listed separately, individual dosages, etc.

Drug: Doxorubicin

25 mg/m2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m2) as part of AI Chemotherapy.

Other Names:

Rubex
Adriamycin
Adriamycin RDF
Adriamycin PFS
Doxorubicin Hydrochloride

Drug: Mesna

Prior to ifosfamide (Day 1) - 500 mg/m2 (20% of ifosfamide dose) given simultaneously with ifosfamide and then daily continuous infusion (Days 1-4 completing infusion on day 4) - 1,500 mg/m2/day (60% of daily ifosfamide dose) for a total of 6 gm/m2. The mesna infusion complete 24 hours after last dose of ifosfamide.

Other Name: Mesnex

Drug: Ifosfamide

2.5 g/m2 IV bolus over 3 hours on days 1, 2, 3, 4 (total dose: 10 g/m2).

Other Name: Ifex

Drug: Vincristine

2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with doxorubicin plus ifosfamide (AI) or AI and vincristine (VAI) is indicated.
Must be 18-65 years of age.
Male and Females of child bearing potential must use acceptable methods of birth control which include oral contraceptives, spermicide with either a condom, diaphragm or cervical cap, us of a intrauterine device (IUD) or abstinence.
Adequate hematologic (ANC >/= 1500/mm^3, platelet count >/= 100,000/mm^3), renal (serum creatinine </= 1.5 mg/dL), hepatic (serum bilirubin count </= 1.5 x normal and SGOT or SGPT </= 3 x normal) functions.
Karnofsky Performance Status >/= 60%
Signed informed consent form.
Patients are required to read and understand English to comply with protocol requirements.

Exclusion Criteria:

Pregnant or lactating women.
Patients with any co-morbid condition which renders patients at high risk of treatment complication.
Known allergy to fosaprepitant or any of its active components.
Patient has uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia or hypertension, or acute myocardial infarction within 3 months.
Patient has an active seizure disorder. (Patients with a previous history of seizure disorders will be eligible for the study, if they have had no evidence of seizure activity, and they have been free of antiseizure medication for the previous 5 years).
Prior surgery or radiotherapy (RT) within 2 weeks of study entry.
Psychological, social, familial, or geographical reasons that would prevent scheduled visits and follow-up.
Patients receiving any medication for pre-existing nausea/vomiting will be excluded.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490060

Contacts

Contact: Saroj Vadhan-Raj, MD

713-792-7966

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030-3722
Principal Investigator: Saroj Vadhan-Raj, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Merck

Investigators

Study Chair:

Saroj Vadhan-Raj, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01490060 History of Changes
Other Study ID Numbers:	2011-0620
Study First Received:	December 8, 2011
Last Updated:	March 28, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

cancer
fosaprepitant
Ifosfamide-based Multi-day Chemotherapy
Chemotherapy-induced nausea and vomiting
CINV
multi-day chemotherapy regimens
antiemetics
adverse effect
doxorubicin plus ifosfamide

AI
AI and vincristine
VAI
aprepitant
prevention
nausea
vomiting
emetogenic chemotherapy

Additional relevant MeSH terms:

Nausea
Vomiting
Sarcoma
Signs and Symptoms, Digestive
Signs and Symptoms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Mesna
Dexamethasone acetate
Dexamethasone
Aprepitant
Dexamethasone 21-phosphate
Isophosphamide mustard
Doxorubicin

Ifosfamide
Vincristine
BB 1101
Serotonin
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on May 21, 2013