Aprepitant for Prevention of Acute and Delayed Nausea and Vomiting in Patients Receiving a High-emetogenic Dose of Cyclophosphamide for Peripheral Blood Stem Cells Harvesting (PG-APRE1)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Azienda Ospedaliera di Perugia.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Azienda Ospedaliera di Perugia
ClinicalTrials.gov Identifier:
NCT01088022
First received: March 16, 2010
Last updated: NA
Last verified: March 2010
History: No changes posted
  Purpose

Title of the study Aprepitant for prevention of acute and delayed nausea and vomiting: a phase III, double-blind, randomized, placebo-controlled trial in patients receiving a high-emetogenic dose of cyclophosphamide for peripheral blood stem cells harvesting

Objective(s) Primary objective: to confirm and extend the investigators preliminary data on the efficacy and safety of combined aprepitant, palonosetron and dexamethasone in preventing CINV after high emetic therapy with cyclophosphamide 3 g/m2 compared with the palonosetron and dexamethasone regimen.

Secondary objective: to monitor peripheral blood stem cell harvest. Methodology Single centre, randomized, double-blind, placebo-controlled phase III trial Endpoints Primary endpoint: the complete response (CR) rate defined as the number of patients with no emetic episodes and no rescue medication in the first 120 hours post-chemotherapy.

Secondary endpoints:

  • CR rates for acute (0-24 h) and delayed (24-120 h) phases;
  • complete control rate (CC) defined as no emetic episode, no rescue medication use and no more than mild nausea;
  • number of emetic episodes;
  • severity of nausea;
  • impact of CINV on daily life as measured by the Functional Living Index-Emesis (FLIE) (total score > 108 = no impact);
  • peripheral blood stem cell harvest;
  • tolerability (adverse events, drug-related adverse events, serious adverse events; discontinuation of treatment due to an adverse event). Adverse events will be classified using NCI Common Toxicity Criteria.

Number of patients A total of 120 patients will be enrolled Inclusion criteria - Male or female patients ≥ 18 years of age

  • Patient is able to understand study procedure and agrees to participate in the study by giving written informed consent.
  • Patient is scheduled to receive a highly emetogenic cyclophosphamide IV chemotherapy (3 g/m2) for autologous PBSC harvesting
  • Karnofsky score ≥60
  • Normal laboratory values
  • Normal ECG
  • HBV-, HCV- and HIV- negative
  • Negative urine pregnancy test for women of childbearing age Treatment Eligible patients will be randomized to receive oral doses of Aprepitant (125 mg day 1, 80 mg days 2 and 3), dexamethasone (8 mg/day for 3 days) and a single intravenous dose of palonosetron (0.25 mg on day 1) versus placebo plus dexamethasone (8 mg/day for 3 days) and a single intravenous dose of palonosetron (0.25 mg on day 1) Duration of study 3 years Criteria for evaluation Efficacy and safety data will be obtained using the patient's daily diary (days 1 through 5) reporting the number of episodes of retching and vomiting, severity of nausea (using a categorical scale of none, mild, moderate or severe), and overall quality of life. The FLIE 8 questionnaire will be completed on days 1 (before starting chemotherapy) and 6 (after chemotherapy). All side effects attributed to this combination therapy will be recorded daily.

Safety parameters: medical history, clinical examination and weight, vital signs, laboratory tests (hematology, chemistry, urine analysis and urine pregnancy test for women of childbearing age).

Statistical aspects Sample size was defined assuming the cumulative incidence rate of the primary endpoint to be 68% in the treatment group and 41% in the control group. With balanced allocation in the two groups, considering a two sided test with α=0.05 and ß=0.20 a total of 110 patients is needed. As few withdrawals and drop-outs are expected a total of 120 patients will be enrolled.

Intention to treat approach will be used for all efficacy analysis. The primary endpoint will be analysed by binomial logistic models. The dependent variable will be vomiting yes/no during the first 120 hours after chemotherapy. Anti-emetic treatment, gender and age will enter as explicative variables.

Dichotomous secondary endpoints will also be analysed by binomial logistic models. Multinomial logistic models will analyze the severity of nausea, stratified in 4 classes.

Generalized Linear Models will investigate quantitative variables such as number of retching or vomiting episodes and peripheral blood stem cell harvest.

In all tests, p value <0.05 will be considered statistically significant. No interim analyses are planned.


Condition Intervention Phase
Nausea
Vomiting
Drug: Aprepitant, Palonosetron, Dexamethasone
Drug: Placebo, Palonosetron, Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Aprepitant for Prevention of Acute and Delayed Nausea and Vomiting: a Phase III, Double-blind, Randomized, Placebo-controlled Trial in Patients Receiving a High-emetogenic Dose of Cyclophosphamide for Peripheral Blood Stem Cells Harvesting

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera di Perugia:

Primary Outcome Measures:
  • Patient's daily diary (days 1 through 5). The FLIE 8 questionnaire will be completed on days 1 and 6. Safety parameters: medical history, clinical examination and weight, vital signs, laboratory tests. [ Time Frame: first 6 days / patient ] [ Designated as safety issue: Yes ]

    Patient's daily diary (days 1 through 5) reporting the number of episodes of retching and vomiting, severity of nausea (using a categorical scale of none, mild, moderate or severe), and overall quality of life. The FLIE 8 questionnaire will be completed on days 1 (before starting chemotherapy) and 6 (after chemotherapy). All side effects attributed to this combination therapy will be recorded daily.

    Safety parameters: medical history, clinical examination and weight, vital signs, laboratory tests.



Estimated Enrollment: 120
Study Start Date: April 2010
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant, Palonosetron, dexametasone Drug: Aprepitant, Palonosetron, Dexamethasone
Aprepitant 125-mg capsule 80-mg capsule 80-mg capsule Palonosetron 0.25 mg i.v. Dexamethasone 8 mg i.v. 8 mg os 8 mg os
Other Name: Emend
Placebo Comparator: Placebo, Palonosetron, Dexamethasone Drug: Placebo, Palonosetron, Dexamethasone
Aprepitant 125-mg placebo capsule 80-mg placebo capsule 80-mg placebo capsule Palonosetron 0.25 mg i.v. Dexamethasone 8 mg i.v. 8 mg os 8 mg os

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients ≥ 18 years of age
  • Patient is able to understand study procedure and agrees to participate in the study by giving written informed consent.
  • Patient is scheduled to receive a highly emetogenic cyclophosphamide IV chemotherapy (3 g/m2) for autologous PBSC harvesting
  • Karnofsky score ≥60
  • Normal laboratory values
  • Normal ECG
  • HBV-, HCV- and HIV- negative
  • Negative urine pregnancy test for women of childbearing age
  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: NCT01088022

Contacts
Contact: Leonardo Flenghi, M.D. +39-0755784110 flenghi@yahoo.it

Locations
Italy
Azienda Ospedaliera di Perugia - Hematology dept. Not yet recruiting
Perugia, Italy, 06100
Principal Investigator: Leonardo Flenghi, M.D.         
Sponsors and Collaborators
Azienda Ospedaliera di Perugia
Investigators
Principal Investigator: Leonardo Flenghi, M.D. Azienda Ospedaliera di Perugia
  More Information

No publications provided

Responsible Party: Leonardo Flenghi M.D., Azienda Ospedaliera di Perugia
ClinicalTrials.gov Identifier: NCT01088022     History of Changes
Other Study ID Numbers: PG-APRE1
Study First Received: March 16, 2010
Last Updated: March 16, 2010
Health Authority: Italy: Ministero della Sanità (AIFA)

Keywords provided by Azienda Ospedaliera di Perugia:
the complete response (CR) rate defined as the number of patients with no emetic episodes and no rescue medication in the first 120 hours post-chemotherapy

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Cyclophosphamide
Dexamethasone
Dexamethasone acetate
Aprepitant
Fosaprepitant
Dexamethasone 21-phosphate
BB 1101
Palonosetron
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 18, 2014