Adjuvant Breast Cancer Study of the Netherlands Working Party for Autotransplantation in Solid Tumors
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Purpose
Objectives of the study:
This randomized multicenter phase II study compares the tolerability, toxicity and quality of life between two high-dose chemotherapy regimens based on cyclophosphamide, thiotepa and carboplatin.
Regimen A: full dose CTC. Regimen B: two courses of CTC (tCTC) with 33% dose reduction.
Primary endpoints are:
- Maximum degree of non-hematological toxicity.
Secondary endpoint:
- Total number of hospital days.
- Quality of life evaluations during and following high-dose chemotherapy (up to 1 year).
- Effect of therapeutic dose monitoring of CTC or tCTC.
Trial design:
This investigation is a multicenter prospective randomized phase II study. Patients eligible for the study will be identified after mastectomy or wide tumor excision with axillary clearance. Following randomization, all patients will receive four courses of cyclophosphamide, epirubicin and fluorouracil (FEC). Patients with early progressive disease at any time will be taken off study. The first chemotherapy course must be given as soon as possible after the surgical procedure, preferably within 3 weeks, but not later than 6 weeks since primary surgery. After the third or fourth FEC course G-CSF is administered and peripheral stem cells will be harvested. All radiation therapy (including radiation therapy administered as part of a breast conserving strategy) must be postponed until all chemotherapy has been concluded.
Questionnaires, comprising the Rotterdam Symptom Checklist (RSCL) and the Short-Form General Health Survey (SF-36) will be sent by mail before randomization, after chemotherapy, 3 months thereafter, further on every l/2 yr till at least 1 year follow-up as performed earlier. [6, 28, 29].
All patients will be randomized before the initiation of chemotherapy.
- The 'standard' treatment arm will include 4 courses of FEC followed by high-dose chemotherapy with a single course of full dose CTC followed by peripheral stem cell reinfusion. Subsequently, conventional external beam radiotherapy to the breast or chest wall and to the regional lymph node areas including the axilla and the parasternal area will be administered following guidelines of the individual center. Patients with hormone receptor positive disease will go on to receive 5 years of tamoxifen. Patients with receptor positive disease who have not entered menopause will be advised to undergo ovarian ablation as well.
- The 'experimental' treatment arm will be identical to the 'standard' one, except that the single course of CTC will be replaced by 2 courses of tCTC each followed by peripheral stem cell reinfusion.
| Condition | Intervention | Phase |
|---|---|---|
|
High-Risk Breast Cancer |
Procedure: stem cell reinfusion Drug: Chemotherapy |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Prospective Randomized Feasibility and Phase II Adjuvant Breast Cancer Study of the Netherlands Working Party for Autotransplantation in Solid Tumors. |
- Maximum degree of non-hematological toxicity.
- Total number of hospital days
- Quality of life evaluations during and following high-dose chemotherapy (up to 1 year)
| Estimated Enrollment: | 50 |
| Study Start Date: | October 2004 |
-
Procedure: stem cell reinfusion
High-dose chemotherapy with the alkylating agent combination CTC appears to add significantly to the efficacy of conventional dose chemotherapy in patients with high-risk breast cancer, provided that the HER-2/neu gene is not amplified in the tumor. As a high-dose chemotherapy regimen, CTC is associated with significant toxicity [31,32]. Although high-dose alkylating therapy seems to be effective, there is virtually nothing known about the dose-response curve for this combination (for a detailed discussion see the classical paper by E. Frei III [32]. If one assumes that the efficacy increase levels off with increasing dose, the efficacy of tCTC might be almost as great as that of CTC, but with considerably less toxicity. In addition, two closely spaced courses of tCTC might further increase the efficacy of the regimen. There are some suggestions that a double transplant may be more effective than a single one, in multiple myeloma and in Ewing sarcoma. A similar suggestion has also been made for breast cancer (study of Nitz et al ref 4, table 1).
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Modified radical mastectomy (or breast conserving surgery) and axillary clearance, histologically confirmed stage IIA, IIB or IIIA adenocarcinoma (excluding supraclavicular lymph nodes) of the breast, with 4 or more involved axillary lymph nodes. Presence of tumor cells near or in the resection margins at microscopic examination is acceptable
- The primary tumor must be immunohistochemically negative for HER-2/neu expression. An immunohistochemistry score of 1+ is also acceptable. A score of 3+ is not acceptable. A score of 2+ is only acceptable if a FISH analysis (or equivalent) has clearly shown that there is no HER-2/neu gene-amplification
- No prior chemotherapy or radiotherapy
- No evidence of distant metastases
- Age < 50 years
- Performance status (ECOG-ZUBROD) 0 or 1;
- Normal bone marrow function, WBC > 4.0 x 109/l, platelets > 100 x 109/l;
- Adequate renal function (creatinine clearance > 60 ml/min.);
- Adequate hepatic function (serum bilirubin < 25 umol/l);
- Study treatment must begin within 6 weeks of surgery;
- No other malignancy except adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin;
- No significant prior or concomitant disorder that might interfere with adherence to the intensive treatment regimen, including but not limited to a history of angina, myocardial infarction or heart failure, severe lung function impairment, peptic ulcer disease, etc.;
- Availability for follow-up.
Contacts and Locations| Netherlands | |
| The Netherlands Cancer Institute | |
| Amsterdam, Netherlands, 1066 CX | |
| Free University Hospital | |
| Amsterdam, Netherlands, 1007 MB | |
| Academic Medical Center | |
| Amsterdam, Netherlands, 1105 AZ | |
| Medisch Spectrum Twente | |
| Enschede, Netherlands, 7511 JX | |
| University Medical Centre Groningen | |
| Groningen, Netherlands, 9713 GZ | |
| Leiden University Medical Centre | |
| Leiden, Netherlands, 2333 JS | |
| University Hospital Maastricht | |
| Maastricht, Netherlands, 6202 AZ | |
| University Medical Centre Nijmegen St. Radboud | |
| Nijmegen, Netherlands, 6525 GA | |
| Erasmus MC, Daniel den Hoed Cancer Center | |
| Rotterdam, Netherlands, 3075 EA | |
| University Medical Centre Utrecht | |
| Utrecht, Netherlands, 3584 CX | |
| Study Director: | Elisabeth G.E. de Vries, MD, PhD | University Medical Centre Groningen |
| Study Director: | Sjoerd Rodenhuis, MD, PhD | The Netherlands Cancer Institute |
More Information
Publications:
| ClinicalTrials.gov Identifier: | NCT00851110 History of Changes |
| Other Study ID Numbers: | METc 2004/110, CKTO 2005-15 |
| Study First Received: | February 23, 2009 |
| Last Updated: | February 24, 2009 |
| Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Keywords provided by University Medical Centre Groningen:
|
high dose breast cancer adjuvant |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases |
Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 22, 2013