Incidence of Chemotherapy-Induced Nausea and Vomiting Associated With Docetaxel-Cyclophosphamide in Early Breast Cancer.

NCT01298193 | Completed Phase 4 Results

• 2 other identifiers: GEICAM/2009-022010-022689-29
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 13

Brief Summary

This is a prospective, multicenter, open label, non-comparative trial in Spain. The primary objective of this study is to determine the complete response, defined as no vomiting and no use of rescue treatment, in women with early-stage breast cancer treated with one cycle of Docetaxel-Cyclophosphamide and active therapy for the prevention of CINV (Chemotherapy-induced nausea and vomiting) day 1, 5-hydroxytryptamine 3 (5-HT3) antagonist plus 3 days of dexamethasone. A second step (efficacy phase) is designed to examine the efficacy and tolerability of aprepitant in the second cycle among patients who failed to the previous CINV prevention treatment. The study will focus on early-stage chemonaive breast cancer patients receiving docetaxel-cyclophosphamide and a 5-HT3 antagonist plus dexamethasone for the CINV prevention. The CINV incidence in those patients will be evaluated on the first cycle. All refractory patients, will be asked to participate in the second phase, where aprepitant on days 1, 2 and 3 will be added to their antiemetic regimen. Assuming a drop out of 5%, 212 patients will be included in the study. It is anticipated that around 48 patients will enter the efficacy phase. The duration of the study, from first patient visit to last patient visit will be approximately 21 months.

Conditions

Breast Cancer

Keywords

Early-stage breast cancer patients

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Response (CR)

  Complete response is defined as no vomiting and no use of rescue treatment within the first cycle of Docetaxel-Cyclophosphamide for the treatment of early-stage breast cancer patients. A vomiting episode is defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes are, by definition, separated by the absence of emesis and retching for at least 1 minute. The timing (date and time) of each vomiting episode will be recorded by the patient in each cycle diary at the time of occurrence. Assessments of efficacy will begin at the initiation of chemotherapy infusion (0 hours) until the morning of Day 6 (approximately 120 hours) after chemotherapy during 1-2 cycles.

  Up to 21 days after cycle 1 of chemotherapy treatment

Secondary Outcomes (8)

• Number of Participants With Complete Response (CR) in Cycle 2 for Patient Without Complete Response in Cycle 1

  Up to cycle 2, and average of 6 weeks

• Number of Participants With Treatment Related Adverse Events (AE) at Cycle 2

  Cycle 2, and average of 3 weeks

• Total Impact of Chemotherapy-Induced Nausea and Vomiting on Daily Life by the Functional Living Index-Emesis Questionnaire in Cycle 1

  Up to day 6

• Impact of Chemotherapy-Induced Nausea on Daily Life by the Functional Living Index-Emesis Questionnaire in Cycle 1

  Up to day 6

• Impact of Chemotherapy-Induced Vomiting on Daily Life by the Functional Living Index-Emesis Questionnaire in Cycle 1

  Up to day 6

Study Arms (1)

Aprepitant

EXPERIMENTAL

Observational phase (first cycle): Day 0 (Dexamethasone 8mg) Day 1 (5-HT3 antagonist, Ondansetron: 8 mg x2, Granisetron: 1mg x2,Tropisetron: 5 mg, Dexamethasone 24 mg) + Chemotherapy (Docetaxel 75mg/m2 and Cyclophosphamide 600mg/m2 ). Days 2 and 3 (Dexamethasone 16 mg). If not complete response: Efficacy phase (second cycle): Day 0 (Dexamethasone 8mg) Day 1 (Aprepitant: 125 mg,5-HT3 antagonist, Ondansetron: 8 mg x2, Granisetron: 1mg x2, Tropisetron: 5 mg, Dexamethasone 12 mg)+ Chemotherapy: Docetaxel 75mg/m2 and Cyclophosphamide 600mg/m2 . Days 2 and 3 (Aprepitant: 1 capsule of 80 mg daily, Dexamethasone 8 mg).

Drug: Aprepitant

Interventions

Aprepitant DRUG

Efficacy phase (second cycle)

Also known as: Rescue therapy:Patients may be provided with a prescription., - 5-HT3 antagonists, - Phenothiazines., - Butyrophenones (e.g., haloperidol or droperidol), - Benzamides (e.g., metoclopramide or alizapride), - Benzodiazepines, - Corticosteroids, - Domperidone

Aprepitant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patient ≥ 18 years of age.
• Patient has a histological confirmed early-stage (I to III) breast cancer.
• Patient is able to understand study procedures and agrees to participate in the study by giving written informed consent.
• Patient is naive to moderate or highly emetogenic chemotherapy per "Hesketh" criteria.
• Patient is scheduled to receive of chemotherapy with Docetaxel-Cyclophosphamide (Docetaxel 75mg/m2 and Cyclophosphamide 600mg/m2) administered every 21 days.
• Patient has a predicted life expectancy ≥ 4 months.
• Functional State 0-1 Eastern Cooperative Oncology Group (ECOG) Scale (see Appendix 12.2).
• Patient has an adequate organ function including the following:
• Bone marrow reserve: Absolute Neutrophil Count \>1500/mm3 and white blood cell (WBC) count \>3000/mm3; Platelet Count \>100.000/mm3
• Hepatic: aspartate aminotransferase (AST) \<2.5 x upper limit of normal; alanine aminotransferase (ALT) \<2.5 x upper limit of normal; Bilirubin within the normal limit.
• Renal: Creatinine \<1.5 x upper limit of normal.
• Premenopausal female patients must demonstrate a negative serum and/or urine pregnancy test within 3 days of study drug administration, and agree to use a double-barrier form of contraception for at least 14 days prior to, throughout and for at least 14 days following the last dose of study medication. Women taking oral contraceptive agents must agree to add a barrier form of contraception. Abstinence is also considered an acceptable form of contraception. (Note: A female patient who is not of reproductive potential is eligible without requiring the use of contraception. A female patient who is not of reproductive potential is defined as one who has either: 1) reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels in the postmenopausal range as determined by the laboratory, or 12 months of spontaneous amenorrhea); 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy; or 3) bilateral tubal ligation.)
• Patient is able to read, understand and complete study questionnaires.

You may not qualify if:

• Patient is scheduled to receive any chemotherapy treatment different to the Docetaxel-Cyclophosphamide chemotherapy.
• Patient has received or will receive radiation therapy to the abdomen, chest or pelvis in the month prior to the study enter.
• Patient has vomited in the 24 hours prior to Treatment Day 1.
• Patient has a history of treatment with emetogenic chemotherapy of moderate or high level per "Hesketh" (classification of emetogenic chemotherapy agents).
• Patient has an active infection (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy which, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk.
• Patient currently uses any illicit drugs, including marijuana, or has current evidence of alcohol abuse as determined by the investigator.
• Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.
• Patient has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk.
• Patient has a history of hypersensitivity to aprepitant, 5-HT3 antagonists, or dexamethasone.
• Patient is pregnant or breast feeding.
• Patient has participated in a study with aprepitant or has taken a non approved (investigational) drug within the last 4 weeks.
• Patient is taking systemic corticosteroid therapy at any dose; topical and inhaled corticosteroids are permitted.
• Patient is taking, or will be taking within 28 days of Day 1 of cycle 2 (cycle in which patients will start taking aprepitant) the following CYP3A4 inducers:
• phenytoin or carbamazepine
• barbiturates

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (13)

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario Príncipe de Asturias

Alcalá de Henares, Madrid, 28805, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Centro Oncológico de Galicia

A Coruña, 15009, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, 25189, Spain

Location

Complejo Hospitalario Xeral-Calde

Lugo, 27004, Spain

Location

Hospital Clínico Universitario San Carlos

Madrid, 28040, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, 46015, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Related Publications (1)

• Llombart-Cussac A, Ramos M, Dalmau E, Garcia-Saenz JA, Gonzalez-Farre X, Murillo L, Calvo L, Morales S, Caranana V, Gonzalez A, Fernandez-Morales LA, Moreno F, Casas MI, Angulo Mdel M, Camara MC, Garcia-Mace AI, Carrasco E, Jara-Sanchez C. Incidence of chemotherapy-induced nausea and vomiting associated with docetaxel and cyclophosphamide in early breast cancer patients and aprepitant efficacy as salvage therapy. Results from the Spanish Breast Cancer Group/2009-02 study. Eur J Cancer. 2016 May;58:122-9. doi: 10.1016/j.ejca.2016.01.015. Epub 2016 Mar 17.

  PMID: 26994459 RESULT

Related Links

• Sponsor's website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aprepitant; Serotonin 5-HT3 Receptor Antagonists; Phenothiazines; Butyrophenones; Haloperidol; Droperidol; Benzamides; Metoclopramide; alizapride; Benzodiazepines; Adrenal Cortex Hormones; Domperidone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Ketones; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; para-Aminobenzoates; Aminobenzoates; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Phenyl Ethers; Phenols; Benzazepines; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Piperidines

Results Point of Contact

• Title: Scientific Director / Medical Lead / Project Manager
• Organization: Spanish Breast Cancer Research Group

geicam@geicam.org

+34916592870

Study Officials

• Study Director

  Hospital Universitario Arnau de Vilanova

  STUDY DIRECTOR

• Study Director

  Fundación Hospital Alcorcón

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients that experiment emesis within the first cycle in spite of the administration of antiemetics, may opt to participate in a subsequent efficacy phase

Study Record Dates

• First Submitted: February 11, 2011
• First Posted: February 17, 2011
• Study Start: May 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: April 1, 2014
• Last Updated: March 7, 2023
• Results First Posted: September 27, 2019

Record last verified: 2023-03

Locations

ES (13)