Content - SAKK 21/12

SAKK 21/12 - Testosterone blocker against breast cancer

We investigate in the phase I/II SAKK21-12 trial, the efficacy of the steroid 4-Hydroxy-Testosterone (4-OH-T) as a treatment for breast cancer in an advanced stage. In other phase I trials and trials with animals, this steroid was able to significantly constrain the growth of TR-positive tumors. Such tumors have receptors for testosterone (proteins that pick up testosterone signals telling the cells to grow). We treat patients with a salve, because 4-OH-T has shown that it has a strong first-pass-effect (large amounts of the active substance do not reach the intended area), when patients are treated with pills. Women with wide spread or locally advanced breast cancer, where a local therapy is not possible, can be part of this trial.  We undertake this trial because despite the fact that the prognosis for patients suffering from breast cancer has improved, still about a quarter of all affected women suffer under recurred or further spread tumors. Moreover, the therapy options for tumors with an aggressive growth are limited.

Study chairs:

Dr. Marcus Vetter, University Hospital Basel, +41 61 265 25 25

Prof. Dr. Beat Thürlimann, Cantonal Hospital of St.Gallen, +41 71 494 18 88

  • Contacts at the hospitals

  • Inclusion criteria

    • Patient must give written informed consent before registration.

    • Post-menopausal women

    • Locally advanced or metastatic, histologically confirmed breast adenocarcinoma requiring therapy and not suitable for local treatment.

      • Stratum A: endocrine responsive-HER2neg BC, specifically: ERpos (≥1%), PRpos (≥1%), HER2neg; or ERpos(≥1%), PRneg, HER2neg

      • Stratum B: triple negative BC (ERneg (<1%), PRneg (<1%), HER2neg) and ARpos (>0%).

    • Positive AR of the most recent formalin-fixed paraffin-embedded (FFPE) biopsy determined by central pathology (Stratum B only). Note: TNBC patients with only locally assessed ARpos (>0%) status are not allowed to enter the trial in Phase II.

      • Stratum A: Patients had 1 line of prior endocrine treatment for advanced disease with a treatment duration of ≥6 months and no evidence of progression at 6 months. No previous chemotherapy for advanced disease is allowed.

      • Stratum B: TN-ARpos BC patients had ≤2 lines of prior chemotherapy treatment for advanced disease.

    • Patient is suitable for endocrine treatment.

    • Presence of ≥1 measurable or evaluable lesion according to RECIST 1.1.

    • Tumor assessment to be performed within 28 days before or on registration.

    • Baseline PRO questionnaire (FACT-ES) has been completed (Phase II only).

    • WHO performance status 0-1.

    • Age ≥ 18 years.

    • Adequate hematological values: hemoglobin ≥100 g/L, ANC ≥1.5x109/L, platelets ≥100x109/L.

    • Adequate hepatic function: total bilirubin ≤1.5xULN, ALT ≤2.5xULN (except for liver metastases ≤5xULN).

    • Adequate renal function: serum creatinine ≤1.5xULN.

  • Exclusion criteria

    • Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.

    • Uncontrolled central nervous system (CNS) metastases, pulmonary carcinomatous lymphangiosis (i.e., >50% invasion), or liver metastases on >1/3 of the liver on ultrasound or computed tomography (CT).

    • Unsuitable for endocrine therapy (e.g. due to rapidly progressing disease or impending 6.2.3complication).

    • Indication for chemotherapy.

    • Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out PRO forms, or interfering with compliance for oral drug intake.

    • Concurrent treatment with other experimental drugs in a clinical trial within 30 days prior to trial treatment start or other anti-cancer therapy within 14 days. Treatment with bisphosphonates/denosumab is allowed. Bisphosphonates/denosumab treatment had to be started at least 3 months before registration.

    • Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes).

    • Known hypersensitivity to trial drug(s) or hypersensitivity to any other component of the trial drugs.

    • Local tumor relapse only that is amenable to surgical treatment.

    • Previous treatment with formestane (4-OHA).

    • Radiotherapy (RT) within 4 weeks prior to treatment start .

    • Concurrent estrogen or progestin therapy in any formulation.

    • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow‐up.

Locations for this trial:

Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Kantonsspital Baden
Im Ergel 1
4600 Baden
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Spital Thurgau, Kantonsspital Frauenfeld
Waldeggstrasse 8A
0 8501 Frauenfeld
Kantonsspital Luzern
Spitalstrasse
0 6000 Luzern
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Kantonsspital Winterthur
Brauerstrasse 15
0 8401 Winterthur
Oncocare/Klinik Engeried
Riedweg 15
0 3012 Bern
OnkoZentrum Zürich
Seestrasse 259
0 8038 Zürich
Hirslanden Klinik St. Anna Luzern
Sankt-Anna-Strasse 32
0 6006 Luzern
Spital STS AG Thun
Krankenhausstrasse 12
0 3600 Thun