Premenopausal Endocrine Responsive Chemotherapy Trial

NCT00066807 | Terminated Phase 3 Results DMC

• 5 other identifiers: IBCSG 26-02 / BIG 4-02NABCI-IBCSG-26-02EU-204012005-002626-59CDR0000318832
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 6

Brief Summary

The PERCHE trial evaluated the worth of adding adjuvant chemotherapy for premenopausal women with steroid hormone receptor positive early invasive breast cancer who receive ovarian function suppression plus either tamoxifen or exemestane for five years. The use of chemotherapy was determined by randomization. The method of ovarian function suppression (GnRH analogue for five years, surgical oophorectomy or ovarian irradiation) and the choice of tamoxifen or exemestane were determined by the investigator or by randomization in the IBCSG 25-02 TEXT trial \[recommended option\]. The trial was terminated early due to poor accrual.

Conditions

Breast Cancer

Keywords

stage IIIA breast cancer; stage I breast cancer; stage II breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival

  For first time at a median follow up approximately 5 years

Secondary Outcomes (3)

• Overall Survival

  For first time at a median follow up approximately 5 years

• Systemic Disease-free Survival

  For first time at a median follow up approximately 5 years

• Sites of First Treatment Failure

  For first time at a median follow up approximately 5 years

Study Arms (2)

OFS plus T or E

EXPERIMENTAL

Ovarian function suppression (OFS) by triptorelin for 5 years or surgical oophorectomy or ovarian irradiation PLUS tamoxifen (T) or exemestane (E) for 5 years.

Drug: exemestane; Drug: tamoxifen; Drug: triptorelin; Procedure: oophorectomy; Procedure: ovarian irradiation

Chemotherapy plus OFS plus T or E

EXPERIMENTAL

Chemotherapy plus ovarian function suppression (OFS) by triptorelin for 5 years or surgical oophorectomy or ovarian irradiation PLUS tamoxifen (T) or exemestane (E) for 5 years.

Drug: chemotherapy; Drug: exemestane; Drug: tamoxifen; Drug: triptorelin; Procedure: oophorectomy; Procedure: ovarian irradiation

Interventions

chemotherapy DRUG

Planned duration of chemotherapy: 2 months if an anthracycline is included (e.g., 4 cycles of EC or AC) or 4 months if no anthracycline is given (e.g., 6 cycles of CMF) is recommended. Unless medically contraindicated, an anthracycline-containing regimen using epirubicin should be given.

Also known as: Ellence, Epirubicin Ebewe

Chemotherapy plus OFS plus T or E

exemestane DRUG

Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.

Also known as: Aromasin

Chemotherapy plus OFS plus T or E; OFS plus T or E

tamoxifen DRUG

Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.

Also known as: Nolvadex

Chemotherapy plus OFS plus T or E; OFS plus T or E

triptorelin DRUG

Triptorelin (GnRH analogue) 3.75 mg by intramuscular injection every 28 days for 5 years from randomization, unless relapse or intolerance should occur earlier or surgical oophorectomy or ovarian irradiation is subsequently performed.

Also known as: GnRH analog, Trelstar Depot

Chemotherapy plus OFS plus T or E; OFS plus T or E

oophorectomy PROCEDURE

Bilateral surgical oophorectomy via laparotomy or laparoscopy.

Chemotherapy plus OFS plus T or E; OFS plus T or E

ovarian irradiation PROCEDURE

Bilateral ovarian irradiation.

Chemotherapy plus OFS plus T or E; OFS plus T or E

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer confined to the breast and axillary nodes * No distant metastatic disease * Tumor detected in the internal mammary chain by sentinel node procedure allowed * Must have undergone 1 of the following procedures for primary breast cancer within the past 12 weeks and have no known clinical residual locoregional disease: * Total mastectomy with or without adjuvant radiotherapy * Breast-conserving surgery (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins clear\* of invasive cancer and ductal carcinoma in situ) followed by radiotherapy NOTE: \*If all other margins are clear, a positive posterior (deep) margin is permitted, provided the excision was performed down to the pectoral fascia and all tumor has been removed OR a positive anterior (superficial; abutting skin) margin is allowed provided all tumor was removed * Prior axillary lymph node dissection or negative axillary sentinel node biopsy required * Patients with microscopically positive axillary sentinel nodes allowed provided they were evaluated on a clinical trial evaluating microscopically positive lymph nodes * No locally advanced, inoperable breast cancer, including any of the following characteristics: * Inflammatory breast cancer * Supraclavicular node involvement * Enlarged internal mammary nodes (unless pathologically negative) * No prior ipsilateral or contralateral invasive breast cancer * Histologically diagnosed synchronous bilateral invasive breast cancer within the past 2 months allowed if the bilateral disease meets all other eligibility criteria * Hormone receptor status: * Estrogen receptor and/or progesterone receptor positive in each tumor * At least 10% of tumor cells positive by immunohistochemistry PATIENT CHARACTERISTICS: Age * Premenopausal Sex * Female Menopausal status * Premenopausal * Estradiol in the premenopausal range after surgery Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * No systemic hepatic disease that would preclude prolonged follow-up Renal * No systemic renal disease that would preclude prolonged follow-up Cardiovascular * No prior deep venous thrombosis and/or embolism unless patient is medically suitable * No systemic cardiovascular disease that would preclude prolonged follow-up Pulmonary * No systemic pulmonary disease that would preclude prolonged follow-up Other * Not pregnant or nursing * Fertile patients must use effective nonhormonal contraception * No other prior or concurrent invasive malignancy except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ without invasion, contralateral or ipsilateral carcinoma in situ of the breast * No prior or concurrent nonbreast invasive malignancy within the past 5 years that is nonrecurrent including any of the following: * Stage I papillary thyroid cancer * Stage Ia carcinoma of the cervix * Stage Ia or b endometrioid endometrial cancer * Borderline or stage I ovarian cancer * No other nonmalignant systemic disease that would preclude prolonged follow-up * No history of noncompliance with medical regimens * No psychiatric, addictive, or other disorder that would preclude study compliance or giving informed consent PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior neoadjuvant or adjuvant chemotherapy * Neoadjuvant or adjuvant trastuzumab (Herceptin®) allowed Endocrine therapy * No prior neoadjuvant or adjuvant endocrine therapy after breast cancer diagnosis * No prior tamoxifen or other selective estrogen-receptor modulator (e.g., raloxifene) within 1 year before the breast cancer diagnosis * No other concurrent oral or transdermal hormonal therapy, including any of the following: * Estrogen * Progesterone * Androgens * Aromatase inhibitors * Hormone replacement therapy * Oral or other hormonal contraceptives, including implant and depot injections * Raloxifene or other selective estrogen-receptor modulators Radiotherapy * See Disease Characteristics * No prior ovarian irradiation Surgery * See Disease Characteristics * No prior bilateral oophorectomy Other * No other prior neoadjuvant therapy * No other concurrent investigational agents * No concurrent bisphosphonates unless bone density has been documented at least 1.5 standard deviations below the young adult normal mean or the patient is participating in a randomized clinical trial setting testing bisphosphonates in the adjuvant breast cancer setting

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• National Cancer Institute (NCI): collaborator
• Breast International Group: collaborator

Study Sites (6)

National Institute of Oncology

Budapest, 1122, Hungary

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Related Publications (1)

• Francis P, Fleming G, Nasi ML, et al.: Tailored treatment investigations for premenopausal women with endocrine responsive (ER+ and/or PGR+) breast cancer: the SOFT, TEXT, and PERCHE trials. [Abstract] The Breast 12 (Suppl 1): A-P104, S44, 2003.

  BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Drug Therapy; Epirubicin; exemestane; Tamoxifen; Triptorelin Pamoate; Gonadotropin-Releasing Hormone; Ovariectomy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Castration; Endocrine Surgical Procedures; Surgical Procedures, Operative; Urogenital Surgical Procedures; Gynecologic Surgical Procedures

Limitations and Caveats

Trial terminated early due to poor accrual. Adverse event data is available ONLY for selected Grade 3-5 AEs for chemotherapy arm. 25 of 29 patients were co-enrolled in TEXT (IBCSG 25-02), which reports AEs and outcomes of endocrine therapy.

Results Point of Contact

• Title: Rudolf Maibach, Executive Officer for International Trial Activities
• Organization: IBCSG

rudolf.maibach@ibcsg.org

+41 31 389 91 96

Study Officials

• Rosalba Torrisi, MD

  Breast International Group, European Institute of Oncology, Milano, Italy

  STUDY CHAIR

• Edith A. Perez, MD

  North American Intergroup, Mayo Clinic Jacksonville, Jacksonville, USA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2003
• First Posted: August 7, 2003
• Study Start: August 1, 2003
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: October 28, 2016
• Results First Posted: April 11, 2016

Record last verified: 2016-09

Locations

HU (1); IT (2); CH (3)