Premenopausal Endocrine Responsive Chemotherapy Trial (PERCHE)

• ClinicalTrials.gov Identifier: NCT00066807
• Recruitment Status: Terminated
• First Posted: August 7, 2003
• Results First Posted: April 11, 2016
• Last Update Posted: October 28, 2016
• Sponsor: International Breast Cancer Study Group
• Collaborators: National Cancer Institute (NCI); Breast International Group
• Information provided by (Responsible Party): International Breast Cancer Study Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: chemotherapy; Drug: exemestane; Drug: tamoxifen; Drug: triptorelin; Procedure: oophorectomy; Procedure: ovarian irradiation	Phase 3

Detailed Description:

OBJECTIVES:

• Compare ovarian function suppression and tamoxifen or exemestane with vs without adjuvant chemotherapy in premenopausal women with endocrine-responsive resected breast cancer.
• Compare the disease-free and overall survival of patients treated with these regimens.
• Compare sites of first treatment failure in patients treated with these regimens.
• Compare the incidence of second nonbreast malignancies in patients treated with these regimens.
• Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.

PLANNED OUTLINE:

This is a randomized, multicenter study. Patients are stratified according to participating center, number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more), method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation), chemotherapy if randomized to arm II (not containing vs containing an anthracycline or taxane), and endocrine agent (tamoxifen vs exemestane vs selected by subsequent randomization in the TEXT trial). Treatment duration is five years.

Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

NOTE: Trial was terminated early due to poor accrual.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women With Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy
• Study Start Date: August 2003
• Actual Primary Completion Date: December 2006
• Actual Study Completion Date: December 2006

Arms and Interventions

Arm	Intervention/treatment
Experimental: OFS plus T or E; 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; Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.; Other Name: Aromasin; Drug: tamoxifen; Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.; Other Name: Nolvadex; Drug: triptorelin; 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.; Other Names: GnRH analog; Trelstar Depot; Procedure: oophorectomy; Bilateral surgical oophorectomy via laparotomy or laparoscopy.; Procedure: ovarian irradiation; Bilateral ovarian irradiation.
Experimental: Chemotherapy plus OFS plus T or E; 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; 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.; Other Names: Ellence; Epirubicin Ebewe; Drug: exemestane; Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.; Other Name: Aromasin; Drug: tamoxifen; Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.; Other Name: Nolvadex; Drug: triptorelin; 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.; Other Names: GnRH analog; Trelstar Depot; Procedure: oophorectomy; Bilateral surgical oophorectomy via laparotomy or laparoscopy.; Procedure: ovarian irradiation; Bilateral ovarian irradiation.

Outcome Measures

Primary Outcome Measures :

1. Disease-free Survival [ Time Frame: For first time at a median follow up approximately 5 years ]

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: For first time at a median follow up approximately 5 years ]
2. Systemic Disease-free Survival [ Time Frame: For first time at a median follow up approximately 5 years ]
3. Sites of First Treatment Failure [ Time Frame: For first time at a median follow up approximately 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Hungary

National Institute of Oncology

Budapest, Hungary, 1122

Italy

Centro di Riferimento Oncologico - Aviano

Aviano, Italy, 33081

European Institute of Oncology

Milan, Italy, 20141

Switzerland

Kantonsspital Graubuenden

Chur, Switzerland, CH-7000

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, 1011

Kantonsspital - St. Gallen

St. Gallen, Switzerland, CH-9007

Sponsors and Collaborators

International Breast Cancer Study Group

National Cancer Institute (NCI)

Breast International Group

Investigators

• Study Chair: 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

More Information

Publications:

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.

• Responsible Party: International Breast Cancer Study Group
• ClinicalTrials.gov Identifier: NCT00066807
• Other Study ID Numbers: IBCSG 26-02 / BIG 4-02; NABCI-IBCSG-26-02 ( International Breast Cancer Study Group ); EU-20401 ( Breast International Group ); 2005-002626-59 ( EudraCT Number ); CDR0000318832 ( Registry Identifier: CT.gov )
• First Posted: August 7, 2003
• Results First Posted: April 11, 2016
• Last Update Posted: October 28, 2016
• Last Verified: September 2016

Keywords provided by International Breast Cancer Study Group:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Tamoxifen; Epirubicin; Exemestane; Triptorelin Pamoate; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Hormonal