CR1447 in Endocrine Responsive-HER2neg and TN-ARpos Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02067741
Recruitment Status : Recruiting
First Posted : February 20, 2014
Last Update Posted : December 21, 2017
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief Summary:

SAKK 21/12 is a stratified, multicenter Phase II first in-human trial with transdermal CR1447 (4-OH-testosterone) and is directed to patients with endocrine responsive-HER2neg and TN-ARpos metastatic or locally advanced breast cancer.

The trial will be conducted in Switzerland with max. 90 patients. CR1447 has a very good safety and tolerability profile and combines two mechanisms of action, interaction with the AR and the aromatase enzyme may have a higher activity than drugs with a single mechanism and might offer the possibility of non-chemotherapy based endocrine therapy to the limited treatment options in TN-ARpos BC. Transdermal application of CR1447 might have the advantage to continuously release of 4-OHT into the blood stream, thus omitting a first pass effect.

In Phase II the main objective is to assess activity and to determine the efficacy and tolerability of CR1447. Phase II will consist of two strata, into which patients will be stratified according to their hormonal receptor status: Stratum A for patients with endocrine responsive-HER2neg disease, regardless of their AR status and Stratum B for patients with triple-negative and determined ARpos disease. Patients with triple-negative disease tested negative for AR will be excluded from the trial.

In both strata patients will be treated with 400 mg of CR1447 until disease progression, patients' wish or physicians' decision to end treatment. Biopsies of one defined metastatic lesion in those patients who gave informed consent will be performed at baseline and within the third week of treatment with CR1447.

Measurement of AR expression, expression of downstream targets of ERα, ERβ, PR, AR, angiogenesis and other translational studies as described in this protocol should help confirming the hypothesis of an increased benefit of CR1447 due to its dual action, efficacy of topical application, tolerability and in deciding whether one should proceed to a large randomized trial.

Condition or disease Intervention/treatment Phase
Metastatic Breast Adenocarcinoma Breast Cancer Drug: CR1447 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Stratified, Multicenter Phase II Trial of Transdermal CR1447 (4-OH-testosterone) in Endocrine Responsive-HER2 Negative and Triple Negative-androgen Receptor Positive Metastatic or Locally Advanced Breast Cancer
Study Start Date : May 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Stratum A - HER2neg BC RD - CR1447
Stratum A - patients with endocrine responsive-HER2neg BC
Drug: CR1447
400 mg, corresponding to two 4 g stick packs applications twice daily
Other Name: 4-OHT

Experimental: Stratum B - ARpos B - CR1447
Stratum B - patients with triple-negative and confirmed ARpos BC
Drug: CR1447
400 mg, corresponding to two 4 g stick packs applications twice daily
Other Name: 4-OHT

Primary Outcome Measures :
  1. Disease control at 24 weeks (DC24) [ Time Frame: at 24 weeks ]

    DC24 is obtained in a patient who achieves complete response (CR) or partial response (PR) within the first 24 ± 2 weeks of treatment or stable disease (SD) for at least 24 weeks after treatment start according to the RECIST 1.1 criteria.

    For patients without CR or PR and no PD before 24 weeks:

    • If the tumor assessment at 24 ± 2 weeks is missing but a later assessment shows SD, the patient will be counted as obtaining DC24.
    • If the tumor assessment at 24 ± 2 weeks is missing and there are no further tumor assessments or the subsequent assessment shows PD, the patient will be counted as not obtaining DC24.

    Tumor assessments showing CR or PR have to be confirmed after 4 weeks.

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 30 days after treatment discontinuation and thereafter monthly until all adverse events related to the trial drug have resolved ]
  2. PK analysis of CR1447 [ Time Frame: at baseline, 3 and 6 months of treatment ]
  3. Estradiol levels during treatment [ Time Frame: at baseline, 3 and 6 months of treatment ]
  4. mRNA expression signature of downstream target genes of the ERα, ERβ, PR, AR and angiogenesis in biopsies [ Time Frame: measured at baseline (day 0) and at treatment and within the third week of treatment ]
  5. Ki67 expression [ Time Frame: measured at baseline (day 0) and at treatment and within the third week of treatment ]
  6. Disease control at 12 weeks (DC12) [ Time Frame: at 12 ± 1 weeks ]
  7. Change in tumor size at 12 weeks [ Time Frame: at 12 weeks ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02067741

Contact: Karin Rothgiesser +41 31 389 91 91

Kantonsspital Aarau Recruiting
Aarau, Switzerland, CH-5001
Contact: Elena Kralidis, MD    +41 62 838 60 53   
Principal Investigator: Elena Kralidis, MD         
Kantonsspital Baden Recruiting
Baden, Switzerland, CH-5404
Contact: Clemens Caspar, MD    +41 56 486 25 11   
Principal Investigator: Clemens Caspar, MD         
Universitätsspital Basel Recruiting
Basel, Switzerland, CH-4031
Contact: Marcus Vetter, MD    +41 61 265 25 25   
Principal Investigator: Marcus Vetter, MD         
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli Recruiting
Bellinzona, Switzerland, CH-6500
Contact: Olivia Pagani, MD    +41 91 811 84 35   
Principal Investigator: Olivia Pagani, MD         
Oncocare / Klinik Engeried Recruiting
Bern, Switzerland, 3012
Contact: Markus Borner, Prof    +41 31 306 95 04   
Principal Investigator: Markus Borner, Prof         
Inselspital Bern Recruiting
Bern, Switzerland, CH-3010
Contact: Manuela Rabaglio, MD    +41 31 632 43 70   
Principal Investigator: Manuela Rabaglio, MD         
Kantonsspital Graubünden Recruiting
Chur, Switzerland, CH-7000
Contact: Roger von Moos, MD, PD    +41 81 256 66 47   
Principal Investigator: Roger von Moos, MD, PD         
Kantonsspital Frauenfeld / Brustzentrum Thurgau Recruiting
Frauenfeld, Switzerland, CH-8501
Contact: Mathias Fehr, MD    +41 52 723 72 53   
Principal Investigator: Mathias Fehr, MD         
Luzerner Kantonsspital Recruiting
Luzern, Switzerland, CH-6000
Contact: Stefan Aebi, Prof    +41 41 205 58 60   
Principal Investigator: Stefan Aebi, Prof         
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Salome Riniker, MD    +41 71 494 19 77   
Principal Investigator: Salome Riniker, MD         
Spital STS AG Recruiting
Thun, Switzerland, CH-3600
Contact: Daniel Rauch, MD    +41 33 226 26 45   
Principal Investigator: Daniel Rauch, MD         
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, CH-8401
Contact: Andreas Müller, MD    +41 52 266 25 52   
Principal Investigator: Andreas Müller, MD         
Onkozentrum - Klinik im Park Recruiting
Zurich, Switzerland, CH-8002
Contact: Andreas Trojan, MD    +41 43 344 33 33   
Principal Investigator: Andreas Trojan, MD         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Study Chair: Marcus Vetter, MD Universitätsspital Basel
Study Chair: Beat Thürlimann, Prof Cantonal Hospital of St. Gallen

Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT02067741     History of Changes
Other Study ID Numbers: SAKK 21/12
SNCTP000000389 ( Other Identifier: SNCTP )
First Posted: February 20, 2014    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
Post-menopausal women
topical application CR1447
endocrine responsive-HER2neg breast cancer
triple negative-androgen receptor positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs