Back to resultsTRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen (TRIUMPH)
Primary Purpose
Breast Cancer
Status
Withdrawn
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Doxorubicin
paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Primary breast cancer, Young women, Ovarian function, Sexual function, Eligible for adjuvant or neoadjuvant chemotherapy, Negative hormone-receptor status
Eligibility Criteria
Inclusion Criteria:
- Age ≤ 40 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Non-metastatic primary invasive carcinoma of the breast eligible for adjuvant or neoadjuvant chemotherapy.
- Negative estrogen (ER) and progesterone receptor (PgR) status.
- Baseline left ventricular ejection fraction (LVEF) ≥50% measured by an echocardiogram or MUGA.
- Interested in maintaining menstrual and/or ovarian function following completion of chemotherapy.
- Known HER2/neu status.
- Negative pregnancy test within 14 days prior to starting chemotherapy.
- Adequate hematologic, hepatic and renal function.
- Signed informed consent.
Exclusion Criteria:
- 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.
- Previous history of amenorrhea > 3 months within the last 2 years (excluding pregnancy).
- Ovarian insufficiency defined as serum FSH > 20 IU/L at the local laboratory, anytime during the menstrual cycle.
- Any ovarian pathology or abnormalities at the screening pelvic ultrasound, except for functional follicular cysts.
- Pregnant or breastfeeding patients.
- 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.
- Concurrent use of any other cytotoxic or hormonal agent, namely GnRH agonists.
- Prior pre-existing peripheral neuropathy of any cause, including diabetes mellitus, alcohol abuse, HIV infection, autoimmune and hereditary neuropathies, amyloidosis, hypothyroidism, vitamin deficiencies.
- Serious cardiac illness, uncontrolled hypertension or medical condition that would affect administration of chemotherapy and compliance to study procedures.
- Known sensitivity to any of the study medications.
Sites / Locations
- GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk
- Jules Bordet Institute
- Hôpital Erasme
- Clinique et Maternité Sainte Elisabeth
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
doxorubicin and paclitaxel
Arm Description
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.
Outcomes
Primary Outcome Measures
Change from baseline in ovarian function
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
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.
Secondary Outcome Measures
Ovarian reserve
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
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
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
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
Patient will complete one validated health-related quality of life questionnaire on peripheral neurotoxicity (FACT-Taxane version 4).
Pregnancy rate after cessation of chemotherapy
Number of pregnancies among participants.
Event-free survival
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).
Full Information
NCT ID
NCT02053597
First Posted
January 27, 2014
Last Updated
September 16, 2015
Sponsor
Jules Bordet Institute
1. Study Identification
Unique Protocol Identification Number
NCT02053597
Brief Title
TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen
Acronym
TRIUMPH
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Withdrawn
Why Stopped
due to evolving scientific knowledge in the field that would make the questions being addressed in the trial less relevant
Study Start Date
October 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jules Bordet Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Primary breast cancer, Young women, Ovarian function, Sexual function, Eligible for adjuvant or neoadjuvant chemotherapy, Negative hormone-receptor status
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
doxorubicin and paclitaxel
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
All patients will receive four cycles of doxorubicin (A) (50 mg/m2)
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from baseline in ovarian function
Description
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.
Time Frame
At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy
Title
Change from baseline in menstrual function
Description
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.
Time Frame
At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy
Secondary Outcome Measure Information:
Title
Ovarian reserve
Description
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.
Time Frame
At 12 months following the end of chemotherapy.
Title
Occurence of Adverse Events
Description
This study will use the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0, for adverse event reporting.
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
Title
Impact of treatment on the behavior of menstruation after menses resumption
Description
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.
Time Frame
At 18, 24 and 60 months after end of chemotherapy.
Title
Evaluate the impact of a cyclophosphamide-free regimen on sexual function
Description
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).
Time Frame
At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.
Title
Evaluate the impact of the regimen on peripheral neurotoxicity
Description
Patient will complete one validated health-related quality of life questionnaire on peripheral neurotoxicity (FACT-Taxane version 4).
Time Frame
At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.
Title
Pregnancy rate after cessation of chemotherapy
Description
Number of pregnancies among participants.
Time Frame
From end of chemotherapy up until 60 months after.
Title
Event-free survival
Description
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).
Time Frame
From the date of registration up until 60 months after the end of chemotherapy.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≤ 40 years.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Non-metastatic primary invasive carcinoma of the breast eligible for adjuvant or neoadjuvant chemotherapy.
Negative estrogen (ER) and progesterone receptor (PgR) status.
Baseline left ventricular ejection fraction (LVEF) ≥50% measured by an echocardiogram or MUGA.
Interested in maintaining menstrual and/or ovarian function following completion of chemotherapy.
Known HER2/neu status.
Negative pregnancy test within 14 days prior to starting chemotherapy.
Adequate hematologic, hepatic and renal function.
Signed informed consent.
Exclusion Criteria:
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.
Previous history of amenorrhea > 3 months within the last 2 years (excluding pregnancy).
Ovarian insufficiency defined as serum FSH > 20 IU/L at the local laboratory, anytime during the menstrual cycle.
Any ovarian pathology or abnormalities at the screening pelvic ultrasound, except for functional follicular cysts.
Pregnant or breastfeeding patients.
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.
Concurrent use of any other cytotoxic or hormonal agent, namely GnRH agonists.
Prior pre-existing peripheral neuropathy of any cause, including diabetes mellitus, alcohol abuse, HIV infection, autoimmune and hereditary neuropathies, amyloidosis, hypothyroidism, vitamin deficiencies.
Serious cardiac illness, uncontrolled hypertension or medical condition that would affect administration of chemotherapy and compliance to study procedures.
Known sensitivity to any of the study medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daphné Tkint de Roodenbeke, MD, PhD
Organizational Affiliation
Jules Bordet Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hatem Azim, MD, PhD
Organizational Affiliation
Jules Bordet Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Isabelle Demeestere, MD, PhD
Organizational Affiliation
Hôpital Erasme
Official's Role
Principal Investigator
Facility Information:
Facility Name
GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk
City
Antwerp
State/Province
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Jules Bordet Institute
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Hôpital Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Clinique et Maternité Sainte Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium
12. IPD Sharing Statement
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TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen
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