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

NCT02053597 | Withdrawn Phase 2

• 2 other identifiers: CE21422013-000173-77
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Cancer

Keywords

Primary breast cancer; Young women; Ovarian function; Sexual function; Eligible for adjuvant or neoadjuvant chemotherapy; Negative hormone-receptor status

Outcome Measures

Primary Outcomes (2)

• 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.

  At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy

• 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.

  At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy

Secondary Outcomes (7)

• Ovarian reserve

  At 12 months following the end of chemotherapy.

• Occurence of Adverse Events

  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

• Impact of treatment on the behavior of menstruation after menses resumption

  At 18, 24 and 60 months after end of chemotherapy.

• Evaluate the impact of a cyclophosphamide-free regimen on sexual function

  At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.

• Evaluate the impact of the regimen on peripheral neurotoxicity

  At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.

Study Arms (1)

doxorubicin and paclitaxel

EXPERIMENTAL

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.

Drug: Doxorubicin; Drug: paclitaxel

Interventions

Doxorubicin DRUG

All patients will receive four cycles of doxorubicin (A) (50 mg/m2)

doxorubicin and paclitaxel

paclitaxel DRUG

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.

doxorubicin and paclitaxel

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jules Bordet Institute: lead

Study Sites (4)

Jules Bordet Institute

Brussels, Brussels Capital, 1000, Belgium

Location

Hôpital Erasme

Brussels, Brussels Capital, 1070, Belgium

Location

Clinique et Maternité Sainte Elisabeth

Namur, Namur, 5000, Belgium

Location

GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk

Antwerp, Wilrijk, 2610, Belgium

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Daphné Tkint de Roodenbeke, MD, PhD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

• Hatem Azim, MD, PhD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

• Isabelle Demeestere, MD, PhD

  Erasme University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2014
• First Posted: February 3, 2014
• Study Start: October 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: September 17, 2015

Record last verified: 2015-09

Locations

BE (4)