Clinical trial NCT02053597: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Primary breast cancer
Young women
Ovarian function
Sexual function
Eligible for adjuvant or neoadjuvant chemotherapy
Negative hormone-receptor status
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
First posted: 2014-02-03
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change from baseline in ovarian function
timeFrame: At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy
measure: Change from baseline in menstrual function
timeFrame: At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy
Secondary outcomes:
measure: Ovarian reserve
timeFrame: At 12 months following the end of chemotherapy.
measure: Occurence of Adverse Events
timeFrame: 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
measure: Impact of treatment on the behavior of menstruation after menses resumption
timeFrame: At 18, 24 and 60 months after end of chemotherapy.
measure: Evaluate the impact of a cyclophosphamide-free regimen on sexual function
timeFrame: At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.
measure: Evaluate the impact of the regimen on peripheral neurotoxicity
timeFrame: At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.
measure: Pregnancy rate after cessation of chemotherapy
timeFrame: From end of chemotherapy up until 60 months after.
measure: Event-free survival
timeFrame: From the date of registration up until 60 months after the end of chemotherapy.
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk
state: Wilrijk
city: Brussels
country: Belgium
facility: Jules Bordet Institute
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte Elisabeth
Study officials:
affiliation: Jules Bordet Institute
name: Daphné Tkint de Roodenbeke, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jules Bordet Institute
name: Hatem Azim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Erasme
name: Isabelle Demeestere, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: