Fosaprepitant in Patients Receiving Ifosfamide-based Regimen

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01490060
First received: December 8, 2011
Last updated: January 31, 2014
Last verified: January 2014
  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:


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.

  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:

  1. 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.
  2. Must be 18-65 years of age.
  3. 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.
  4. 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.
  5. Karnofsky Performance Status >/= 60%
  6. Signed informed consent form.
  7. Patients are required to read and understand English to comply with protocol requirements.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Patients with any co-morbid condition which renders patients at high risk of treatment complication.
  3. Known allergy to fosaprepitant or any of its active components.
  4. 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.
  5. 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).
  6. Prior surgery or radiotherapy (RT) within 2 weeks of study entry.
  7. Psychological, social, familial, or geographical reasons that would prevent scheduled visits and follow-up.
  8. Patients receiving any medication for pre-existing nausea/vomiting will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030-3722
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Saroj Vadhan-Raj, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
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: January 31, 2014
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
Fosaprepitant
Aprepitant
Dexamethasone 21-phosphate
Liposomal doxorubicin
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

ClinicalTrials.gov processed this record on August 20, 2014