Breast Cancer MedDRA version: 14.0 Level: PT Classification code 10006201 Term: Breast cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.0 Level: PT Classification code 10006202 Term: Breast cancer stage IV System Organ Class: 10029104 - Neoplasms beni
Conditions
Interventions
Product Name: Filgrastim
Product Code: MK-4214
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Filgrastim
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient understands the study procedures, alternative treatments available, the risks involved with the study, and agrees to participate by giving written informed consent. 2. Female who is = 18 years of age on the day of signing informed consent. 3. Female who is not free from menses for > 1 year, or posthysterectomy/oophorectomy, or surgically sterilized, is willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with Visit 1 through 6 Months after the last dose of chemotherapy in the Randomized Blinded Trial or Open-Label Extension. Adequate contraceptive methods include for example, intrauterine device, diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. 4. Patient has been diagnosed with Stage II, III, or IV breast cancer, classification according to American Joint Committee on Cancer, 7th Edition (See Appendix 6.6), and based on clinical disease characteristics is considered by the investigator to be an appropriate candidate for treatment with the combination of doxorubicin and docetaxel at the protocol-specified full doses. NOTE: Patient must receive full dose of chemotherapy in Cycle 1 in order to be eligible for randomization. 5. Patients with Stage II or III disease who have not received prior chemotherapy. Patients with Stage IV disease who have not received prior chemotherapy for metastatic disease (prior neo-adjuvant and/or adjuvant chemotherapy for early stage breast cancer is allowed, provided time since last dose of chemotherapy is > 1 year). Prior or concomitant hormonal breast cancer therapy is allowed. 6. Patient satisfies the Eastern Cooperative Oncology Group performance status (ECOG) of = 2 (Appendix 6.4). 7. In those cases of prior neo-adjuvant or adjuvant use of an anthracycline, patient will be able to receive a full course of doxorubicin-docetaxel chemotherapy at the protocol-specified doses for 4-6 cycles (duration of therapy in accordance with institutional standards of care) without exceeding a total cumulative anthracycline dose of 550 mg/m2. The calculation should include doxorubicin received on the current study as well as anthracyclines and/or anthracenediones received in prior adjuvant chemotherapy. 8. Patient has adequate cardiac, bone marrow, liver, kidney and other organ function for chemotherapy with doxorubicin in combination with docetaxel at the protocolspecified dosing, according to general treatment guidelines and institutional standards of care. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 175
Exclusion criteria
Exclusion criteria: 1. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of receiving study therapy. 2. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study or within 6 months after the last dose of chemotherapy. 3. Patient has known sickle cell disorder. 4. Patient has received a systemic anti-infective agent within 72 hours of randomization. 5. Patient has received filgrastim, pegfilgrastim or any granulocyte-colony-stimulating factors (G-CSF) or recombinant granulocyte–macrophage colony-stimulating factors (GM-CSF) or is expected to receive erythropoietin, darbepoetin, or another colonystimulating factor other than study drug for the duration of the study. NOTE: Prior erythropoietin or darbepoetin use > 6 weeks prior to randomization is permissible. 6. Patient is expected to take lithium during the course of the trial (lithium may potentiate the release of neutrophils). 7. Patient has a hypersensitivity to filgrastim or pegfilgrastim or any of the excipients of MK-4214 or Neupogen. 8. Patient has received biologics as targeted therapy (e.g. Herceptin within 4 weeks of randomization into the study. 9. Patient has undergone radiation therapy within 4 weeks of randomization with the exception of spot radiation (irradiation to = 25% of total marrow) for the treatment of bone metastases. 10. Patient has had prior bone marrow or stem cell transplant. 11. Patient has hypersensitivity or intolerance to filgrastim or any of the excipients of MK-4214. 12. Patient is allergic or intolerant to latex (latex is a component of the pre-filled syringes of MK-4214 and Neupogen 13. Patient has known central nervous system (CNS) metastases and/or carcinomatous meningitis. 14. Patient has undergone a major surgical procedure within 4 weeks prior to study start. 15. Patient with a history of a prior malignancy, other than breast cancer, with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by her treating physician. 16. Patient is taking anticoagulation therapy (with exception of low dose aspirin), or has a known bleeding disorder, or a history of increased bleeding tendencies, spontaneously or subsequent to minor traumas. 17. Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To compare DSN, defined as the number of days with ANC < 0.5 x 109/L, during Cycle 1, in patients with breast cancer receiving MK-4214 or Neupogen™ as adjunct to chemotherapy with doxorubicin in combination with docetaxel.; Secondary Objective: 1. To evaluate the incidence of FN, defined as an oral temperature of = 38.3ºC, persisting for at least one hour, concurrent with an ANC < 0.5 x 109/L within 24 hours of the fever, by cycle and across all cycles of chemotherapy in patients treated with MK-4214 or Neupogen™ . 2. To evaluate the incidence of hospitalization due to infection by cycle and across all cycles of chemotherapy in patients treated with MK-4214 or Neupogen™ 3. To evaluate the usage (incidence) of IV anti-infective agents by cycle and across all cycles of chemotherapy in patients treated with MK-4214 or Neupogen™ 4. To assess the safety and tolerability of MK-4214 and Neupogen™ 5. To evaluate the incidence of anti-rG-CSF antibodies in patients treated with MK-4214 or Neupogen™ ;Primary end point(s): Duration of severe neutropenia in Cycle 1 as defined as the number of days with ANC < 0.5 x 109/L, during Cycle 1.;Timepoint(s) of evaluation of this end point: Planned analysis is after the last patient has their last visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Febrile Neutropenia, defined as an oral temperature of = 38.3°C persisting for at least an hour, concurrent with an ANC < 0.5 109/L within 24 hours of the fever, by cycle, and across all cycles of chemotherapy - Hospitalization for infection by cycle and across all cycles of chemotherapy - Hospitalization for IV anti-infectives by cycle and across all cycles of chemotherapy - Depth of ANC nadir in Cycle 1 -Time to ANC recovery in Cycle 1. This time begins at the start of chemotherapy and is defined as the number of days required for the ANC to reach ANC = 2 x 109/L. - Immunogenicity testing to assess the potential development of antibodies directed against G-CSF ; Timepoint(s) of evaluation of this end point: Planned analysis is after the last patient has her last visit, with the exception of immunogenicity testing, which will be completed after patients have their 6-month follow up visit (about 2 years after last patient enrolls). | — |
Countries
Argentina, Belarus, Brazil, Chile, Croatia, Georgia, Germany, India, Italy, Latvia, Lithuania, Macedonia, the former Yugoslav Republic of, Mexico, Peru, Philippines, Romania, Russian Federation, Serbia, South Africa, Ukraine
Contacts
Public ContactSteven Hildemann
MSD Regional Business Support Center GmbH
Outcome results
None listed