Incidence of Chemotherapy-Induced Nausea and Vomiting Associated With Docetaxel-Cyclophosphamide in Early Breast Cancer.
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Vomiting
Intervention: Aprepitant
Intervention description: Efficacy phase (second cycle)
Intervention MeSH terms: Phenothiazine; Droperidol; Haloperidol; Aprepitant; Metoclopramide; Domperidone; Alizapride; Serotonin 5-HT3 Receptor Antagonists
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Patients that experiment emesis within the first cycle in spite of the administration of antiemetics, may opt to participate in a subsequent efficacy phase
Masking: None (Open Label)
Enrollment: 212.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Early-stage breast cancer patients

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.
    

Eligibility 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 naive to moderate or highly emetogenic chemotherapy per "Hesketh" criteria.

          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 Eastern Cooperative Oncology Group (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 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.

          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
             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.)

         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" (classification of emetogenic chemotherapy agents).

          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
             initiated at least 48 hours before enrollment.