TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen | RxWiki

TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen

Overview[ - collapse ][ - ]

Purpose	Recently, there has been a rising trend of delaying childbearing and hence more women are diagnosed with breast cancer before completing their families. Given the continuous decline in recurrences and death secondary to breast cancer and the reassuring data on the safety of pregnancy following breast cancer more women are inquiring into the possibility of preserving fertility following chemotherapy. The challenge remains in using a regimen that is devoid of cyclophosphamide, but is as effective as the standard regimens that incorporate cyclophosphamide. The combination doxorubicin (50 mg/m2) and paclitaxel (200 mg/m2) (AP) followed by 12 weeks of paclitaxel (80 mg/m2) (P) emerges as a treatment option with convincing results regarding its effectiveness in the early setting, and could be potentially associated with less ovarian toxicity being devoid of cyclophosphamide.
Condition	Breast Cancer
Intervention	Drug: Doxorubicin Drug: paclitaxel
Phase	Phase 2
Sponsor	Jules Bordet Institute
Responsible Party	Jules Bordet Institute
ClinicalTrials.gov Identifier	NCT02053597
First Received	January 27, 2014
Last Updated	February 12, 2014
Last verified	January 2014

Tracking Information[ + expand ][ + ]

First Received Date	January 27, 2014
Last Updated Date	February 12, 2014
Start Date	February 2014
Estimated Primary Completion Date	December 2019
Current Primary Outcome Measures	Change from baseline in ovarian function [Time Frame: At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy] [Designated as safety issue: No]Ovarian function will be evaluated using serum FSH, estradiol and AMH. Ovarian failure is defined as serum FSH >40 IU/L. Ovarian insufficiency is defined as serum FSH level from 20 - 40 IU/L. Ovarian reserve will be evaluated by serum AMH. Adequate ovarian reserve is defined as serum AMH >1 ng/ml. Menstrual function will be evaluated by collecting information of the 1st day of last menstrual cycle, and cycle length (days between two menstruating periods). Ovarian function will be evaluated using serum FSH, estradiol and AMH. Ovarian failure is defined as serum FSH >40 IU/L. Ovarian insufficiency is defined as serum FSH level from 20 - 40 IU/L. Ovarian reserve will be evaluated by serum AMH. Adequate ovarian reserve is defined as serum AMH >1 ng/ml. Change from baseline in menstrual function [Time Frame: At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy] [Designated as safety issue: No]Menstrual function will be evaluated by collecting information of the 1st day of last menstrual cycle, and cycle length (days between two menstruating periods). In patients menstruating regularly after 12 months of chemotherapy cessation, information on menstrual cycle will be collected at 6-monthly intervals until developing menopause, disease recurrence, becoming pregnant, whichever occurs earlier, for a maximum period of 5 years after end of chemotherapy.
Current Secondary Outcome Measures	Ovarian reserve [Time Frame: At 12 months following the end of chemotherapy.] [Designated as safety issue: No]A serum AMH determination will be performed at 12 months after the end of chemotherapy. An adequate ovarian reserve is defined as serum AMH >1 ng/ml at that timepoint. Occurence of Adverse Events [Time Frame: From the signature of informed consent until until the end of study treatment/treatment discontinuation visit 30 days after the last dose of study medication] [Designated as safety issue: Yes]This study will use the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0, for adverse event reporting. Impact of treatment on the behavior of menstruation after menses resumption [Time Frame: At 18, 24 and 60 months after end of chemotherapy.] [Designated as safety issue: No]In patients menstruating regularly after 12 months of chemotherapy cessation, information on menstrual cycles will be collected at 18, 24 and up to 60 months after end of chemotherapy, until developing menopause, disease recurrence or becoming pregnant, whichever occurs earlier. This information will include the date of last menstrual period, menstruation duration and if 2 or more consecutive menstrual cycles were missed, allowing to assess irregularity and possible cessation of menses. Evaluate the impact of a cyclophosphamide-free regimen on sexual function [Time Frame: At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.] [Designated as safety issue: No]Patient will complete two validated health-related quality of life questionnaires, one on menopausal symptoms (FACT-ES version 4) and the other on sexual functioning (FSAQ). Evaluate the impact of the regimen on peripheral neurotoxicity [Time Frame: At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.] [Designated as safety issue: Yes]Patient will complete one validated health-related quality of life questionnaire on peripheral neurotoxicity (FACT-Taxane version 4). Pregnancy rate after cessation of chemotherapy [Time Frame: From end of chemotherapy up until 60 months after.] [Designated as safety issue: No]Number of pregnancies among participants. Event-free survival [Time Frame: From the date of registration up until 60 months after the end of chemotherapy.] [Designated as safety issue: No]Event-free survival will be calculated from the date of registration to the study to developing local, loco-regional or distant metastasis, secondary malignancies or death. All patients will be considered for the primary efficacy analysis (ITT analysis).

Descriptive Information[ + expand ][ + ]

Brief Title	TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen
Official Title	A Phase II TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen Composed of Doxorubicin and Paclitaxel
Brief Summary	Recently, there has been a rising trend of delaying childbearing and hence more women are diagnosed with breast cancer before completing their families. Given the continuous decline in recurrences and death secondary to breast cancer and the reassuring data on the safety of pregnancy following breast cancer more women are inquiring into the possibility of preserving fertility following chemotherapy. The challenge remains in using a regimen that is devoid of cyclophosphamide, but is as effective as the standard regimens that incorporate cyclophosphamide. The combination doxorubicin (50 mg/m2) and paclitaxel (200 mg/m2) (AP) followed by 12 weeks of paclitaxel (80 mg/m2) (P) emerges as a treatment option with convincing results regarding its effectiveness in the early setting, and could be potentially associated with less ovarian toxicity being devoid of cyclophosphamide.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Breast Cancer
Intervention	Drug: Doxorubicin All patients will receive four cycles of doxorubicin (A) (50 mg/m2) Drug: paclitaxel All patients will receive four cycles paclitaxel (P) (200 mg/m2), given on a three-weekly basis for four cycles, followed by weekly paclitaxel (P) (80 mg/m2) for twelve weeks.
Study Arm (s)	Experimental: doxorubicin and paclitaxel All patients will receive four cycles of doxorubicin (A) (50 mg/m2) and paclitaxel (P) (200 mg/m2), given on a three-weekly basis for four cycles, followed by weekly paclitaxel (P) (80 mg/m2) for twelve weeks.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	45
Estimated Completion Date	December 2019
Estimated Primary Completion Date	September 2015
Eligibility Criteria	Inclusion Criteria: 1. Age ≤ 40 years. 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. 3. Non-metastatic primary invasive carcinoma of the breast eligible for adjuvant or neoadjuvant chemotherapy. 4. Negative estrogen (ER) and progesterone receptor (PgR) status. 5. Baseline left ventricular ejection fraction (LVEF) ≥50% measured by an echocardiogram or MUGA. 6. Interested in maintaining menstrual and/or ovarian function following completion of chemotherapy. 7. Known HER2/neu status. 8. Negative pregnancy test within 14 days prior to starting chemotherapy. 9. Adequate hematologic, hepatic and renal function. 10. Signed informed consent. Exclusion Criteria: 1. History of prior malignant disease (breast or non-breast) or non-malignant condition which was treated with chemotherapy, pelvic irradiation or any therapy that could potentially affect ovarian function. 2. Previous history of amenorrhea > 3 months within the last 2 years (excluding pregnancy). 3. Ovarian insufficiency defined as serum FSH > 20 IU/L at the local laboratory, anytime during the menstrual cycle. 4. Any ovarian pathology or abnormalities at the screening pelvic ultrasound, except for functional follicular cysts. 5. Pregnant or breastfeeding patients. 6. Inability or unwillingness to use effective contraception during and up to 3 months after the last dose of study medication. Effective methods include the following: non-hormonal intrauterine device, barrier method - condoms, diaphragm - also in conjugation with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed. 7. Concurrent use of any other cytotoxic or hormonal agent, namely GnRH agonists. 8. Prior pre-existing peripheral neuropathy of any cause, including diabetes mellitus, alcohol abuse, HIV infection, autoimmune and hereditary neuropathies, amyloidosis, hypothyroidism, vitamin deficiencies. 9. Serious cardiac illness, uncontrolled hypertension or medical condition that would affect administration of chemotherapy and compliance to study procedures. 10. Known sensitivity to any of the study medications.
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Ana Catarina Pinto, MD, MSc +32(0)2 541 3099 ana-catarina.pinto@bordet.be
Location Countries	Belgium

Administrative Information[ + expand ][ + ]

NCT Number	NCT02053597
Other Study ID Numbers	CE2142
Has Data Monitoring Committee	No
Information Provided By	Jules Bordet Institute
Study Sponsor	Jules Bordet Institute
Collaborators	Not Provided
Investigators	Principal Investigator: Ana Catarina Pinto, MD, MSc Jules Bordet InstitutePrincipal Investigator: Hatem Azim, MD, PhD Jules Bordet InstitutePrincipal Investigator: Isabelle Demeestere, MD, PhD Hôpital Erasme
Verification Date	January 2014

Locations[ + expand ][ + ]

GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk	Antwerp, Wilrijk, Belgium, 2610 Contact: Annemie Prové, MD \| +32 (0)3 443 37 37 Principal Investigator: Annemie Prové, MD Not yet recruiting
Jules Bordet Institute	Brussels, Belgium, 1000 Contact: Philippe Aftimos, MD \| aftimos@bordet.be Principal Investigator: Ana Catarina Pinto, MD, MSc Not yet recruiting
Hôpital Erasme	Brussels, Belgium, 1070 Contact: Philippe Simon, MD, PhD \| +32 (0)2 555 3685 \| philippe.simon@erasme.ulb.ac.be Principal Investigator: Philippe Simon, MD, PhD Not yet recruiting
Clinique et Maternité Sainte Elisabeth	Namur, Belgium, 5000 Contact: Géraldine Mineur \| +32 (0)81 720 548 \| geraldine.mineur@cmsenamur.be Principal Investigator: Peter Vuylsteke, MD, PhD Not yet recruiting