Postoperative Use of Zoledronic Acid in Breast Cancer Patients After Neoadjuvant Chemotherapy (NATAN)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Austrian Breast & Colorectal Cancer Study Group
Novartis Pharmaceuticals
Information provided by (Responsible Party):
German Breast Group
ClinicalTrials.gov Identifier:
NCT00512993
First received: August 3, 2007
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to determine the event-free survival (EFS) after zoledronic acid for 5 years versus no postoperative treatment in patients with "chemo-insensitive" breast cancer (ypT1-4 and/or ypN1-3) after preoperative anthracycline/taxane containing chemotherapy


Condition Intervention Phase
Breast Cancer
Drug: Zoledronic acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Open Phase III Study Comparing the Postoperative Use of Zoledronic Acid Versus no Treatment in Patients With Histological Tumor Residuals After Preoperative Anthracycline and Taxane Containing Chemotherapy for Primary Breast Cancer

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • The event-free survival (EFS) after zoledronic acid for 5 years versus no postoperative treatment in patients with "chemo-insensitive" breast cancer (ypT1-4 and/or ypN1-3) after preoperative anthracycline/taxane containing chemotherapy. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The overall survival in both treatment arms. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • The EFS with respect to the interval between surgery and randomization. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • The bone-metastasis free-survival in both arms. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • The toxicity of and compliance to zoledronic acid. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • The predictive value of primary breast tumor response on the effect of postoperative treatment. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • The prognostic impact of chemotherapy induced amenorrhea in premenopausal patients. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 654
Study Start Date: December 2004
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment
Patients receive zoledronic acid (4mg) for 5 years. Additionally patients receive standard endocrine, radiologic and trastuzumab treatment, respectively
Drug: Zoledronic acid
Infusion of zoledronic acid (4 mg) every 4 weeks for six doses, followed by every 3 months for 8 doses, followed by every 6 months for 5 doses
Other Name: Zometa
No Intervention: Observation
Patients will be under observation and receive standard endocrine, radiologic and trastuzumab treatment, respectively

Detailed Description:

The study is restricted to patients having had primary systemic chemotherapy for stage II and III breast cancer. Participation in a preoperative chemotherapy trial investigating anthracycline and taxane based regimen is allowed, but not mandatory for all patients. Patients must have significant remaining tumor tissue in the breast and/or axillary lymph node. This implies resistance to further chemotherapy and a clinically relevant risk for relapse. Bisphosphonates have a distinct mechanism of action and have demonstrated efficacy in the treatment of breast cancer with metastasis to the bone as well as adjuvant treatment after surgery of primary breast cancer. The 3rd generation bisphosphonate zoledronic acid has a favorable toxicity profile and can be conveniently given to patients over a long term period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures;
  • Complete baseline documentation sent to GBG;
  • Prior preoperative chemotherapy for at least 4 cycles, of which at least two must contain a taxane and an anthracycline;
  • Completely resected unilateral or bilateral primary carcinoma of the breast with histologically detectable tumor residuals (ypT1-4) and/or histology confirmed involvement of axillary nodes (ypN1-3). Sentinel node biopsy is allowed, but complete axillary clearance is mandatory in node positive cases;
  • A maximum interval of 3 years from date of axillary surgery to entering this trial;
  • Age 18 years or older;
  • Karnofsky index >= 70%;
  • Life expectancy of at least 10 years, disregarding the diagnosis of cancer;
  • No clinical evidence of local recurrence or distant metastases. Complete staging work-up: All patients must have breast ultrasound, chest X-ray, ultrasound or CT scan of the liver within 3 months prior to registration, as well as (bilateral) mammography or breast MRI and bone scan within 8 months prior to registration. In case of a positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated;
  • Adequate renal and hepatic function (serum creatinine, bilirubin, and transaminases within 1.5 × upper normal range);
  • Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating center.

Exclusion Criteria:

  • Known hypersensitivity reaction to the investigational compound;
  • Prior postoperative chemotherapy;
  • Prior treatment with bisphosphonates since breast cancer surgery;
  • Pregnant or lactating patients. Patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration and must implement adequate non-hormonal contraceptive measures (barrier methods, intra uterine contraceptive devices, sterilization) during study treatment;
  • History of diseases with influence on bone metabolism, such as Paget's disease of bone and primary hyperparathyroidism or osteoporosis requiring treatment at the time of study entry or considered likely to become necessary within the six months
  • Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
  • Prior or concomitant secondary malignancy (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix)
  • Concurrent treatment with other experimental drugs or any other anti-cancer therapy;
  • Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute;
  • Serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or > 12.0 mg/dl (3.00 mmol/L)
  • Concurrent treatment with sex hormones. Prior treatment must be stopped before study entry;
  • Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures.
  • Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)
  • Male patients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00512993

  Show 93 Study Locations
Sponsors and Collaborators
German Breast Group
Austrian Breast & Colorectal Cancer Study Group
Novartis Pharmaceuticals
Investigators
Study Chair: Gunter von Minckwitz, Prof. MD GBG Forschungs GmbH, Hessen, Germany
Study Chair: Peter Dubsky, MD Austrian Breast & Colorectal Cancer Study Group
  More Information

Additional Information:
No publications provided

Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT00512993     History of Changes
Other Study ID Numbers: GBG 36, NATAN, ABCSG 29
Study First Received: August 3, 2007
Last Updated: May 22, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Breast Group:
Postoperative treatment with zoledronic acid
Preoperative anthracycline/taxane containing chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014