A Prospective, Multicenter, Open-label 12 Week Neoadjuvant Phase II Trial Optimizing Taxane Therapy in Elderly Patients With Low Response

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
TEVA
Information provided by (Responsible Party):
West German Study Group
ClinicalTrials.gov Identifier:
NCT02214381
First received: July 31, 2014
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

Comparison of pre-surgical Myocet/ Cyclophosphamide (MC) q3w followed by either MC or Paclitaxel - depending on early response assessment by ultrasound or by toxicity for elderly non frail primary breast cancer patients with increased risk of relapse.


Condition Intervention Phase
Early Primary Breast Cancer in the Elderly.
Drug: Myocet
Drug: Cyclophosphamide
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Open-label Comparison of Pre-surgical Myocet/ Cyclophosphamide (MC) q3w Followed by Either MC or Paclitaxel - Depending on Early Response Assessment by Ultrasound or by Toxicity for Elderly Non Frail Primary Breast Cancer Patients With Increased Risk of Relapse.

Resource links provided by NLM:


Further study details as provided by West German Study Group:

Primary Outcome Measures:
  • Comparison of pCR rates in patients with early response and no severe toxicity (Group 1) and in other patients (Group 2). [ Time Frame: After 5 years of follow-up. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of febrile neutropenia (FN) after 1 x MC in patients with primary prophylaxis (PP) vs. others. [ Time Frame: After 5 years of follow-up. ] [ Designated as safety issue: Yes ]
  • Toxicity in the 4 x MC versus 2 x MC followed 6 x Pac arm as measured by adverse events. [ Time Frame: After 5 years of follow-up. ] [ Designated as safety issue: Yes ]
  • Number of pCR in non-responders to MC. [ Time Frame: After 5 years of follow-up. ] [ Designated as safety issue: Yes ]
  • G-CSF use in terms of primary or secondary prophylaxis per patient including occurence febrile neutropenia per patient per cycle [ Time Frame: After 5 years of follow-up. ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: July 2014
Estimated Study Completion Date: July 2021
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mycet/Cyclophosphamid
4 x Myocet 60 mg/m² q3w in combination with 4 x cyclophosphamide 600 mg/m² q3w depending on early response assessment by ultrasound or on toxicity profile.
Drug: Myocet
Other Name: Doxorubicin
Drug: Cyclophosphamide
Active Comparator: Myocet/Cyclophosphamide/Paclitaxel
2 x Myocet 60 mg/m² q3w in combination with 2 x cyclophosphamide 600 mg/m² q3w followed by 6 x paclitaxel 80 mg/m² q1w depending on early response assessment by ultrasound or on toxicity profile.
Drug: Myocet
Other Name: Doxorubicin
Drug: Cyclophosphamide Drug: Paclitaxel

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

General Inclusion Criteria for ADAPT:

  • Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)
  • Candidate for chemotherapy on the basis of conventional criteria
  • Histologically confirmed unilateral primary invasive carcinoma of the breast
  • Clinical T1 - T4a-c
  • All clinical N (cN)
  • No clinical evidence for distant metastasis (M0)
  • Known HR status and HER2 status (local pathology)
  • Tumor block available for central pathology review
  • Performance Status ECOG <= 1 or KI >= 80%
  • Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
  • The patient must be accessible for treatment and follow-up
  • Patients must qualify for neoadjuvant treatment
  • LVEF > 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to chemotherapy)

    • Laboratory requirements :

      • Leucocytes ≥ 3.5 x 109/L
      • Platelets ≥ 100 x 109/L
      • Hemoglobin ≥ 10 g/dL
      • Total bilirubin ≤ 1 x ULN
      • ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x UNL
      • Creatinine ≤ 175 µmol/L (2 mg/dl)

Additional inclusion criteria ADAPT Elderly:

  • ≥ 70 years old
  • Charlson scale ≤ 2
  • HR+/HER2- disease: if RS and sequential testing are available N0-1/RS 12-25/poor response or N0-1/RS ≥26
  • All G3 with Ki-67 ≥40% in tumors >1cm
  • All N2
  • All TN
  • All subtypes

General Exclusion Criteria for ADAPT:

  • Known hypersensitivity reaction to the compounds or incorporated substances
  • Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
  • Non-operable breast cancer including inflammatory breast cancer
  • Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
  • Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry (concurrent participation in non-interventional post authorization safety studies not influencing the primary study endpoints is allowed, e.g. WSG PROTROCA for evaluation of primary/secondary G-CSF prophylaxis)
  • Male breast cancer
  • Sequential breast cancer
  • Reasons indicating risk of poor compliance
  • Patient not able to consent

Additional Exclusion Criteria ADAPT Elderly:

  • Known polyneuropathy ≥ grade 2
  • Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study
  • Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.)
  • Uncompensated cardiac function (current unstable ventricular arrhythmia requiring treatment, history of symptomatic CHF NYHA classes II-IV), history of myocardial infarction or unstable angina pectoris within 12 months of enrollment, history of severe hypertension, CAD - coronary artery disease)
  • Severe dyspnea
  • Pneumonitis
  • Abnormal blood values:
  • Thrombocytopenia > CTCAE grade 1
  • Increases in ALT/AST > CTCAE grade 1
  • Hypokalaemia > CTCAE grade 1
  • Neutropenia > CTCAE grade 1
  • Anaemia > CTCAE grade 1
  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: NCT02214381

Locations
Germany
Ev. Krankenhaus Bethesda Brustzentrum Niederrhein
Moenchengladbach, Germany, 41061
Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern
Munich, Germany, 81337
Sponsors and Collaborators
West German Study Group
TEVA
Investigators
Principal Investigator: Nadia Harbeck, Prof. Dr. Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern, Munich, Germany
Study Chair: Ulrike Nitz, Prof. Dr. Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
  More Information

No publications provided

Responsible Party: West German Study Group
ClinicalTrials.gov Identifier: NCT02214381     History of Changes
Other Study ID Numbers: WSG-AM06 / ADAPT Elderly
Study First Received: July 31, 2014
Last Updated: August 7, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by West German Study Group:
breast
cancer
elderly

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Cyclophosphamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 22, 2014