Clinical trial NCT02214381: A Prospective, Multicenter, Open-label 12 Week Neoadjuvant Phase II Trial Optimizing Taxane Therapy in Elderly Patients With Low Response
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Early Primary Breast Cancer
Keywords: breast cancer
elderly
Lead sponsor: West German Study Group
Sponsor class: OTHER
Collaborators: name: Teva Pharmaceuticals USA
First posted: 2014-08-12
Enrollment: 80
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Comparison of pCR rates in patients with early response and no severe toxicity (Group 1) and in other patients (Group 2).
timeFrame: After 5 years of follow-up.
Secondary outcomes:
measure: Incidence of febrile neutropenia (FN) after 1 x MC in patients with primary prophylaxis (PP) vs. others.
timeFrame: After 5 years of follow-up.
measure: Toxicity in the 4 x MC versus 2 x MC followed 6 x Pac arm as measured by adverse events.
timeFrame: After 5 years of follow-up.
measure: Number of pCR in non-responders to MC.
timeFrame: After 5 years of follow-up.
measure: G-CSF use in terms of primary or secondary prophylaxis per patient including occurence febrile neutropenia per patient per cycle
timeFrame: After 5 years of follow-up.
Other outcomes:
Locations:
city: Moenchengladbach
country: Germany
facility: Ev. Krankenhaus Bethesda Brustzentrum Niederrhein
city: Munich
country: Germany
facility: Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern
Study officials:
affiliation: Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern, Munich, Germany
name: Nadia Harbeck, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
name: Ulrike Nitz, Prof. Dr.
role: STUDY_CHAIR
References: