Panther: A Study Comparing Biweekly and Tailored EC-T Versus Three Weekly FEC-T in Breast Cancer Patients

Condition(s) targeted: Breast Cancer

Intervention: Epirubicin, cyclophosphamide, docetaxel (Drug); Epirubicin, cyclophosphamide, 5-fluorouracil, docetaxel (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Karolinska University Hospital

Official(s) and/or principal investigator(s):
Jonas Bergh, MD, PhD, Principal Investigator, Affiliation: Karolinska University Hospital

Overall contact:
Mats Hellström, Phone: +46 8 51773677, Email: mats.hellstrom@karolinska.se

This is an adjuvant, open, prospective, randomized study to compare:

A. Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week, to

B. Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel (FEC→T).

Patients with primary node-positive or high risk lymph node negative breast cancer will be eligible for the study.

The primary objective of the phase 3 study is to compare breast cancer relapse-free survival (BCRFS) between the dtEC→dtT and FE100C→T. To detect a five-year BCRFS difference of 0. 710 to 0. 790 about 762 patients per arm will be needed. They will be recruited during three years and followed another two years for breast cancer events.

Secondary objectives are to compare

1. Distant disease-free survival (DDFS)

2. Event-free survival and

3. Overall survival

4. Health-related quality of life

5. Outcome in relation to tumour biological factors and polymorphism patterns

Tumour tissue will be obtained and stored for studies of prognostication and therapy prediction.

Official title: PANTHER. A Randomized Phase 3 Study Comparing Biweekly and Tailored Epirubicin + Cyclophosphamide Followed by Biweekly Tailored Docetaxel (dtEC→dtT) Versus Three Weekly Epirubicin + Cyclophosphamide + 5-fluorouracil Followed by Docetaxel (FEC→T) in Lymph Node Positive or High Risk Lymph Node Negative Breast Cancer Patients

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Breast cancer relapse-free survival

Secondary outcome:

Distant disease-free survival

Event-free survival

Overall survival

Health-related quality of life

Outcome in relation to tumour biological factors and polymorphism patterns

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Histological proven invasive primary breast cancer, with at least 5 (recommended 10)

removed axillary lymph nodes OR negative sentinel node biopsy performed for the node negative cohort. Interval between definitive surgery that includes axillary lymph node dissection and registration must be less than 60 days. Paraffin block from the primary tumour must be retained (not mandatory for Austrian sites). Frozen tumour tissue is strongly recommended to be stored.

- Receptor negative or positive tumours with 1 or more positive axillary lymph nodes

(more than 0. 2 mm) OR axillary node negative breast cancers if the primary tumour is larger than 20 mm and receptor negative (Er and Pgr with no receptor content) and being Elston grade III. In Germany high risk node negative breast cancer patients are not eligible until labelling for docetaxel includes node-negative disease.

- Macroscopically and microscopically free margins after radical surgery (no cancer

cells at borders of resection).

- No proven distant metastases (negative chest/pulmonary X-ray, bone scintigram (when

clinical signs of skeletal metastases or elevated ALP) supplemented with normal conventional X-ray of hot spots, normal liver function test and haematological function tests; when abnormal values, CT or ultrasound of the liver, patient can be included if no metastases are demonstrated.

- Female age 18-65.

- Ambulant patients (ECOG 1 or less).

- No major cardiovascular morbidity NYHA I or II. (Appendix 3).

- Written informed consent according to the local ethics committee requirements.

- Patients of childbearing potential should have a negative pregnancy test within seven

days of registration. (In Austria, pregnancy tests have to be repeated monthly during the treatment phase).

Exclusion Criteria:

- Previous neo-adjuvant treatment.

- Non-radical surgery (histopathological positive margins).

- Proven distant metastases.

- Pregnancy or lactation.

- Other serious medical condition.

- Previous or concurrent malignancies at other sites, except basal cell carcinoma

and/or squamous cell carcinoma in situ of the skin or cervix. Patients with previous breast cancer (invasive and/or ductal carcinoma in situ) in the other breast without loco-regional (large lung volumes) radiotherapy, without objective findings for relapse, with > 5 years since diagnosis can be included.

- Abnormal laboratory values precluding the possibility to safely deliver the used

cytotoxic agents in the study.

- Hypersensitivity to drugs formulated in polysorbate 80.

- Peripheral neuropathy grade ≥2.

Mats Hellström, Phone: +46 8 51773677, Email: mats.hellstrom@karolinska.se

Central Hospital, Gävle, Sweden; Recruiting
Per Edlund, MD, PhD, Principal Investigator
Johan Ahlgren, MD, PhD, Sub-Investigator

Sahlgrenska University Hospital, Göteborg, Sweden; Recruiting
Zakaria Einbeigi, MD, PhD, Principal Investigator
Per Karlsson, MD, PhD, Sub-Investigator
Stig Holmberg, MD, PhD, Sub-Investigator

Central Hospital, Karlstad, Sweden; Recruiting
Eva Karlsson, PhD
Lena Hermansson, RN
Eva Karlsson, PhD, Principal Investigator

Linköping University Hospital, Linköping, Sweden; Recruiting
Annika Malmström, MD, Principal Investigator

Lund University Hospital, Lund, Sweden; Recruiting
Per Malmström, MD, PhD, Principal Investigator

Malmö General University Hospital, Malmö, Sweden; Recruiting
Martin Söderberg, MD, Principal Investigator

Karolinska University Hospital, Dept of Oncology, Stockholm, Sweden; Recruiting
Jonas Bergh, Email: jonas.bergh@ki.se
Tommy Fornander, MD, PhD, Sub-Investigator
Sam Rotstein, MD, PhD,, Sub-Investigator
Birgitta Wallberg, MD, Sub-Investigator

Central Hospital, Sundsvall, Sweden; Recruiting
Lena Carlsson, MD, Principal Investigator

Norrlands University Hospital, Umeå, Sweden; Recruiting
Nils-Olof Bengtsson, MD, Principal Investigator

Uppsala Academic Hospital, Uppsala, Sweden; Recruiting
Henrik Lindman, MD, PhD, Principal Investigator

Örebro University Hospital, Örebro, Sweden; Recruiting
Kenneth Villman, MD, Principal Investigator

Swedish website for the study

Starting date: February 2007
Last updated: August 26, 2010