Pharmacologic Interaction Between Ifosfamide and Aprepitant in Treated Patients With Soft Tissue Sarcoma (IPIAP-STM)

This trial is a multicentric study aiming to assess the evolution of the serum ifosfamide concentrations and its serum metabolites in patients treated for an Soft Tissue Sarcoma and co-exposed to Aprepitant.

The study will be conducted on a population of patients treated with Doxorubicin and Ifosfamide. The Aprepitant can be prescribed to patients from cycle 2, according to the current recommendations. Doxorubicin, Ifosfamide and Aprepitant will be administered in the context of routine care. The follow-up during the treatment period and the clinical, biological and radiological assessments will be performed according to the standard of each centre.

Patients will be followed during the two first cycles of treatment. For the pharmacokinetic study, blood samples will be collected at different time points during the 2 treatment cycles.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Patients starting a treatment with Doxorubicin and Ifosfamide

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Montpellier, France, 34298
    • Institut régional du Cancer de Montpellier (ICM)
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse - Oncopole

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Anatomopathologic diagnosis of soft tissue sarcoma (localized, local recidive or metastatic).
3. Patient receiving doxorubicin and ifosfamide chemotherapy (treatment decided during Multidisciplinary consultation meetings) (neoadjuvant, adjuvant or palliative treatment).

4. Screening laboratory values must meet the following criteria:

   1. Hemoglobin > 9.0 g/dL, Neutrophils > 1500/mm3, Platelets > 100000/mm3
   2. Creatinine clearance (MDRD formula) > 60ml/min.
   3. AST/ALT < 2.5 x ULN (5 x ULN in patients with hepatic metastasis).
5. Evaluable disease (measurable per RECIST or not), if applicable.
6. Patient must provide written informed consent prior to any study specific procedures.
7. Patient affiliated to a Social Health Insurance in France.

Exclusion Criteria:

1. Previous treatment with Ifosfamide.
2. Patient who has already started doxorubicin and ifosfamide treatment.

3. Any medical condition that can increase the patient's risk

   1. Active infection
   2. Active hepatitis or cirrhosis
   3. Recipients of organ transplants or immunocompromised patients, including Human Immunodeficiency Virus (HIV) infection
4. Pregnant or breastfeeding women
5. Any psychological, familial, geographical or sociological condition which does not allow to respect the medical follow-up and/or compliance to study procedure
6. Patient protected by law

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients starting a treatment with Doxorubicin and Ifosfamide	Drug: Patients starting a treatment with Doxorubicin and Ifosfamide; 9 blood samples will be collected at each Cycle: Cycle 1 (Day 1-Day 2-Day 3); Cycle 2 (Day 1-Day 2-Day 3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evolution of 2d-Ifo plasma concentrations between the 1st cycle (without co-exposure to the Aprepitant) and the 2nd cycle (with co-exposure to the Aprepitant)	Cycle 2 Day 3 for each patient

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03	Cycle 3 Day 1 for each patient
Evolution of plasma concentrations of ifosfamide and its serum metabolites between the first and second cycles	Cycle 3 Day 1 for each patient
The rate of objective responses determined according to the criteria RECIST v 1.1	Cycle 3 Day 1 for each patient

Collaborators and Investigators

• Sponsor: Institut Claudius Regaud

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2018
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: April 20, 2018
• First Submitted That Met QC Criteria: April 20, 2018
• First Posted (Actual): May 2, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Doxorubicin; Soft Tissue Sarcoma; Ifosfamide; Aprepitant
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Ifosfamide; Doxorubicin
• Other Study ID Numbers: 17 SARC 04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No