Adjuvant Breast Cancer Study of the Netherlands Working Party for Autotransplantation in Solid Tumors

February 24, 2009 updated by: University Medical Center Groningen

A Prospective Randomized Feasibility and Phase II Adjuvant Breast Cancer Study of the Netherlands Working Party for Autotransplantation in Solid Tumors.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • The Netherlands Cancer Institute
      • Amsterdam, Netherlands, 1105 AZ
        • Academic Medical Center
      • Amsterdam, Netherlands, 1007 MB
        • Free University Hospital
      • Enschede, Netherlands, 7511 JX
        • Medisch Spectrum Twente
      • Groningen, Netherlands, 9713 GZ
        • University Medical Centre Groningen
      • Leiden, Netherlands, 2333 JS
        • Leiden University Medical Centre
      • Maastricht, Netherlands, 6202 AZ
        • University Hospital Maastricht
      • Nijmegen, Netherlands, 6525 GA
        • University Medical Centre Nijmegen St. Radboud
      • Rotterdam, Netherlands, 3075 EA
        • Erasmus MC, Daniel den Hoed Cancer Center
      • Utrecht, Netherlands, 3584 CX
        • University Medical Centre Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion criteria:

  1. 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
  2. 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
  3. No prior chemotherapy or radiotherapy
  4. No evidence of distant metastases
  5. Age < 50 years
  6. Performance status (ECOG-ZUBROD) 0 or 1;
  7. Normal bone marrow function, WBC > 4.0 x 109/l, platelets > 100 x 109/l;
  8. Adequate renal function (creatinine clearance > 60 ml/min.);
  9. Adequate hepatic function (serum bilirubin < 25 umol/l);
  10. Study treatment must begin within 6 weeks of surgery;
  11. No other malignancy except adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin;
  12. 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.;
  13. Availability for follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum degree of non-hematological toxicity.

Secondary Outcome Measures

Outcome Measure
Total number of hospital days
Quality of life evaluations during and following high-dose chemotherapy (up to 1 year)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Study Director: Elisabeth G.E. de Vries, MD, PhD, University Medical Center Groningen
  • Study Director: Sjoerd Rodenhuis, MD, PhD, The Netherlands Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Study Registration Dates

First Submitted

February 23, 2009

First Submitted That Met QC Criteria

February 24, 2009

First Posted (Estimate)

February 25, 2009

Study Record Updates

Last Update Posted (Estimate)

February 25, 2009

Last Update Submitted That Met QC Criteria

February 24, 2009

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • METc 2004/110
  • CKTO 2005-15

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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