Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer
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| ClinicalTrials.gov Identifier: NCT00194792 |
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Recruitment Status :
Terminated
First Posted : September 19, 2005
Results First Posted : June 6, 2017
Last Update Posted : July 11, 2017
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Estrogen Receptor-positive Breast Cancer HER2-negative Breast Cancer Progesterone Receptor-positive Breast Cancer Stage I Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer | Drug: exemestane Drug: triptorelin pamoate Drug: capecitabine Drug: methotrexate Drug: vinorelbine tartrate Drug: paclitaxel Procedure: therapeutic conventional surgery Radiation: radiation therapy Other: laboratory biomarker analysis | Phase 2 |
PRIMARY OBJECTIVES:
I. To assess the pathologic response rate in patients with operable breast cancer treated with a two part, neoadjuvant regimen consisting of complete hormonal blockade (CHB) for 2 weeks followed by four three-week cycles of Xeloda, Methotrexate and Navelbine with continuation of complete hormonal blockade.
SECONDARY OBJECTIVES:
I. To assess the clinical response rate in patients with surgically resectable breast cancer treated with complete hormonal blockade and four three-week cycles of Xeloda, Methotrexate and Navelbine.
II. To assess the toxicity associated with these regimens. III. To assess the relapse rate, overall and disease-free survival in patients with operable breast cancer when treated with neoadjuvant CHB and XMN + CHB followed by adjuvant treatment using XMN or Taxol.
IV. To assess whether the phenotype of breast cancer changes with treatment. V. To assess whether phenotypic changes in breast tumors predict outcome.
OUTLINE:
NEOADJUVANT CHB: Patients receive exemestane orally (PO) daily for 14 weeks. Premenopausal patients also receive triptorelin pamoate intramuscularly (IM) once monthly for 4 months beginning 2 weeks before the initiation of exemestane.
NEOADJUVANT CHEMOTHERAPY: Patients receive capecitabine PO twice daily (BID) on days 1-14 and methotrexate intravenously (IV) and vinorelbine ditartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses.
SURGERY: Patients then undergo definitive surgical resection with or without radiation therapy.
ADJUVANT CHEMOTHERAPY: Patients with microscopic complete response (pCR) or disease that has been down-staged to =< 1 cm with no positive nodes receive capecitabine PO BID on days 1-14 and methotrexate IV and vinorelbine ditartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses. Patients with down-staged T and 0 or 1 positive node receive paclitaxel IV over 1 hour once weekly for 12 weeks.
ADJUVANT HORMONAL THERAPY: Patients receive hormonal therapy for 5 years.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 28 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, A Phase II Study |
| Study Start Date : | August 2005 |
| Actual Primary Completion Date : | July 2011 |
| Actual Study Completion Date : | July 2011 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (hormone therapy and chemotherapy)
See detailed description
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Drug: exemestane
Given PO
Other Names:
Drug: triptorelin pamoate Given IM
Other Names:
Drug: capecitabine Given PO
Other Names:
Drug: methotrexate Given IV
Other Names:
Drug: vinorelbine tartrate Given IV
Other Names:
Drug: paclitaxel Given IV
Other Names:
Procedure: therapeutic conventional surgery Undergo lumpectomy or mastectomy Radiation: radiation therapy Undergo radiation therapy
Other Names:
Other: laboratory biomarker analysis Correlative studies |
- Number of Participants With Clinical Response [ Time Frame: 1 month ]Defined as a > 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease.
- Number of Participants With Microscopic Pathologic Complete Response and Macroscopic Pathologic Complete Response [ Time Frame: From date of treatment start to surgery ]Defined as no evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection and the examining pathologist cannot identify gross residual tumor mass in the surgical specimen.
- Disease-free Survival [ Time Frame: Up to 5 years ]Kaplan-Meier estimate assessed at 5 years
- Overall Survival [ Time Frame: Up to 5 years ]From the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive. Kaplan-Meier estimate assessed at 5 years.
- Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities [ Time Frame: Monthly during neoadjuvant treatment and then 6 months following treatment (including surgery) ]Count of all incidences of grade 2, 3, 4 adverse events and fatal toxicities
- Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation [ Time Frame: During adjuvant and neoadjuvant chemotherapy ]Count of patients with dose reduction, treatment interruption, or treatment discontinuation.
- Correlation of Molecular Markers With Response, Time to Progression, and Survival [ Time Frame: Weekly during CHB and XMN and pacitaxel ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Have histologically confirmed, operable ER or PR +, HER2/neu negative, radiographically measurable breast cancer > 1cm (Operable lesions are T1c - T3 and N0 - N2a; histologic confirmation should be by core needle biopsy only)
- Be chemotherapy naive
- Have an ECOG performance status of =< 2
- Be assessed for menopausal status (For study purposes, postmenopausal is defined as: a prior documented bilateral oophorectomy, or a history of at least 12 months without spontaneous menstrual bleeding, or age 60 or older with a prior hysterectomy without oophorectomy, or Age less than 60 with a prior hysterectomy without oophorectomy [or in whom the status of the ovaries is unknown], with a documented FSH level demonstrating confirmatory elevation in the postmenopausal range for the lab)
- All premenopausal patients must have a baseline FSH and LH
- ANC >= 1,500
- Platelet count >= 100,000
- Serum creatinine =< 1.5 x IULN
- Estimated creatinine clearance > 50 ml/min
- Have staging studies and tumor assessment prior to registration
- Bone density exam must be done within the first 3 months of complete hormonal blockade
- Have a negative pregnancy test within seven days prior to registration if of childbearing potential
- Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures
Exclusion Criteria:
- Primary tumor =< 1 cm, not measurable; inflammatory disease
- Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded (Women of childbearing potential who are not using a reliable and appropriate contraceptive method are excluded; patients must agree to continue contraception for 30 days from the last study drug administration)
- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil
- Previous enrollment in an investigational drug study within the last 4 weeks
- Evidence of distant metastatic disease
- Prior chemotherapy or hormonal therapy for breast cancer
- Prior malignancy other than adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, other stage I or II cancer from which the patient has been disease free for at least 5 years
- History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance with oral drug intake
- Any other life-threatening illness (e.g. serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication or myocardial infarction
- Major surgery within four weeks of the start of study treatment without complete recovery
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
- Known, existing uncontrolled coagulopathy
- Unwillingness to give informed consent
- Unwillingness to participate or inability to comply with the protocol for the duration of the study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00194792
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: | Hannah Linden | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| Responsible Party: | Hannah Linden, Principal Investigator, University of Washington |
| ClinicalTrials.gov Identifier: | NCT00194792 |
| Other Study ID Numbers: |
6277 NCI-2010-00549 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) |
| First Posted: | September 19, 2005 Key Record Dates |
| Results First Posted: | June 6, 2017 |
| Last Update Posted: | July 11, 2017 |
| Last Verified: | June 2017 |
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Vinorelbine Capecitabine Methotrexate Exemestane Triptorelin Pamoate Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents |
Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors |