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

• Status: Unknown status
• Trial end date: 2020-10-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: West German Study Group
• Collaborators: TEVA; Teva Pharmaceuticals USA
• Treatments: Albumin-Bound Paclitaxel; Cyclophosphamide; Doxorubicin; Paclitaxel

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