Incidence of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With the Docetaxel-Cyclophosphamide Regimen in Early Breast Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT01298193
First received: February 11, 2011
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

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-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 chemonaïve 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.


Condition Intervention Phase
Breast Cancer
Drug: Aprepitant
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Open Label, Non-comparative Trial to Determine the Incidence of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With the Docetaxel-Cyclophosphamide Regimen in Early Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Spanish Breast Cancer Research Group:

Primary Outcome Measures:
  • To determine the incidence of complete response, 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 [ Time Frame: Up to 21 days after cycle 1 of chemoteraphy treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate in cycle 2 the efficacy of aprepitant (days 1, 2 and 3) as secondary prevention in patients without complete response in cycle 1 [ Time Frame: Up to 21 days after cycle 2 of chemoteraphy treatment ] [ Designated as safety issue: No ]
  • To evaluate the toxicity of study drug (cycle 2) in those patients. [ Time Frame: Up to 30 days after completion of or discontinuation from the study. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 212
Study Start Date: May 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant

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).

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
Efficacy phase (second cycle)

  Eligibility

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

Inclusion Criteria:

  1. Female patient ≥ 18 years of age.
  2. Patient has a histological confirmed early-stage (I to III) breast cancer.
  3. Patient is able to understand study procedures and agrees to participate in the study by giving written informed consent.
  4. Patient is naïve to moderate or highly emetogenic chemotherapy per Hesketh criteria (see Appendix 7.1).
  5. Patient is scheduled to receive of chemotherapy with Docetaxel-Cyclophosphamide (Docetaxel 75mg/m2 and Cyclophosphamide 600mg/m2) administered every 21 days.
  6. Patient has a predicted life expectancy ≥ 4 months.
  7. Functional State 0-1 ECOG Scale (see Appendix 12.2).
  8. Patient has an adequate organ function including the following:

    • Bone marrow reserve: Absolute Neutrophil Count >1500/mm3 and WBC count >3000/mm3; Platelet Count >100.000/mm3
    • Hepatic: AST (aspartate transaminase) <2.5 x upper limit of normal; ALT (alanine transaminase) <2.5 x upper limit of normal; Bilirubin within the normal limit.
    • Renal: Creatinine <1.5 x upper limit of normal.
  9. 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 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.)
  10. Patient is able to read, understand and complete study questionnaires.

Exclusion Criteria:

  1. Patient is scheduled to receive any chemotherapy treatment different to the Docetaxel-Cyclophosphamide chemotherapy.
  2. Patient has received or will receive radiation therapy to the abdomen, chest or pelvis in the month prior to the study enter.
  3. Patient has vomited in the 24 hours prior to Treatment Day 1.
  4. Patient has a history of treatment with emetogenic chemotherapy of moderate or high level per Hesketh (see Appendix 7.1).
  5. 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.
  6. Patient currently uses any illicit drugs, including marijuana, or has current evidence of alcohol abuse as determined by the investigator.
  7. Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.
  8. 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.
  9. Patient has a history of hypersensitivity to aprepitant, 5-HT3 antagonists, or dexamethasone.
  10. Patient is pregnant or breast feeding.
  11. Patient has participated in a study with aprepitant or has taken a non approved (investigational) drug within the last 4 weeks.
  12. Patient is taking systemic corticosteroid therapy at any dose; topical and inhaled corticosteroids are permitted.
  13. 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
    • rifampicin or rifabutin
    • St. John's Wort
  14. Patient is taking, or will be taking within 7 days of Day 1 of cycle 2 the following CYP3A4 substrates:

    • terfenadine
    • cisapride
    • astemizole
    • pimozide
  15. Patient is taking, or will be taking within the 7 days of Day 1 of cycle 2 the following CYP3A4 inhibitors:

    • clarithromycin
    • ketoconazole, itraconazole
  16. Patient will be taking an antiemetic within 48 hours of Day 1 of cycle 2. Prohibited antiemetics include:

    • 5-HT3 antagonists (ondansetron, granisetron, dolasetron, tropisetron or palonosetron)
    • phenothiazines (e.g., prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine)
    • butyrophenones (e.g., haloperidol or droperidol)
    • benzamides (e.g., metoclopramide or alizapride)
    • domperidone
    • cannabinoids
    • herbal therapies with potential antiemetic properties
    • scopolamine
    • cyclizine
  17. Patient has used benzodiazepines or opiates, except for single daily doses of triazolam, temazepam or midazolam in the 48 hours prior to Day 1 of cycle 2. Continuation of chronic benzodiazepines or opiate therapy is permitted provided it was iniciated at least 48 hours before enrollment.
  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: NCT01298193

Locations
Spain
Corporación Sanitaria Parc Taulí
Sabadell, Barcelona, Spain, 08208
Hospital Universitario Principe de Asturias
Alcalá de Henares, Madrid, Spain
Fundación Hospital de Alcorcón
Alcorcón, Madrid, Spain, 28922
Centro Oncológico de Galicia
A Coruña, Spain, 15009
Complejo Hospitalario Universitario A Coruña
A Coruña, Spain, 15006
Hospital del Mar
Barcelona, Spain, 08003
Hospital Clinic i Provincial
Barcelona, Spain, 08036
Complejo Hospitalario de Jaén
Jaén, Spain, 23007
Hospital Universitario Arnau de Vilanova
Lleida, Spain
Complexo Hospitalario Xeral Calde
Lugo, Spain
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital Arnau de Vilanova
Valencia, Spain, 46015
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain, 50009
Sponsors and Collaborators
Spanish Breast Cancer Research Group
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Antonio Llombart, MD Hospital Universitario Arnau de Vilanova
Principal Investigator: Carlos Jara, MD Fundación Hospital Alcorcón
  More Information

Additional Information:
No publications provided

Responsible Party: Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01298193     History of Changes
Other Study ID Numbers: GEICAM/2009-02, 2010-022689-29
Study First Received: February 11, 2011
Last Updated: June 7, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Spanish Breast Cancer Research Group:
Early-stage breast cancer patients

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Cyclophosphamide
Aprepitant
Fosaprepitant
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 18, 2014