Achtung, öffnet in einem neuen Fenster. | Drucken |

RAD001 - English summary - RADAR

A randomized discontinuation phase II study to determine the efficacy of RAD001 in breast cancer patients with bone metastases

Current Status: Open to Accrual

Trial design

Prospective, multi-centre, placebo-controlled, randomized discontinuation phase II study

design_radar_engl

Randomized discontinuation design of Radar

Treatment

Treatment with 10 mg RAD001 daily will be applied for 8 weeks. Thereafter the therapy response will be evaluated. Patients with complete or partial response should continue with RAD001. If a stable disease with no change of the metastases is ensured, patients will be randomised to receiving either RAD001 10 mg or placebo in 1:1 ratio. Patients with progression of disease after the 8 week run in treatment with RAD001 have to be taken off study.

Patient population

Inclusion criteria:

  1. Primary tumour or metastasis negative or positive (≥ 10% positive stained cells) for oestrogen- and/or progesterone receptor detected by immunohistochemistry
  2. Single or multiple bone metastasis (x-ray, CT or MRI) as only metastatic site
  3. Hormone receptor positive patients should have received an aromatase inhibitor in any given previous breast cancer therapy. Endocrine pre-treatment for metastatic bone disease is allowed. Previous treatment with bisphosphonates is allowed
  4. Up to one previous chemotherapy for metastatic disease is allowed
  5. Absolute neutrophil count ≥1,500 cells/µl, platelet count ≥100,000 cells/µl

Exclusion criteria:

  1. Concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive and/or replacement therapy)
  2. Need for chemotherapy or irradiation of bone metastasis during study treatment.
  3. Uncompensated diabetes mellitus; fasting value of blood sugar of >120 (mg/dl)
  4. Patients being treated with drugs recognized as being strong inhibitors or inducers of theisoenzyme CYP3A (e.g. Rifabutin, Rifampicin, Clarithromycin, Keto-conazole, Itroconazole, Ritinavir, Telithromycin, Erythromycin, Verapamil, Diltazem, see Appendix) within the last 5 days or the expected need for these treatments during study participation
  5. Pregnant or nursing women
  6. The patient is not accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or Coinvestigator's site

Primary Objective

To determine the time to progression (TTP) in patients with no change in bone metastases after an 8 week run in treatment with RAD001 compared to placebo.
Secondary Objectives

  1. To determine the objective response rate after 8 weeks of RAD00
  2. To determine the TTP in patients with a response after 8 weeks of RAD001
  3. To determine the overall clinical benefit defined as CR, PR or stable disease > 24 weeks for patients continuing RAD001 after the 8 week run in phase
  4. To determine the TTP separately for each stratum
  5. To evaluate the safety and toxicity of RAD001
  6. To assess the frequency of bone related events
  7. To assess changes of pain intensity during treatment

Primary Endpoint

Any progression of disease or disease related death of a patient belonged to the group with no change in metastases after a 8 week run in treatment with RAD001.

Study Report

RAD001 is an orally biovailable and well tolerated rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin). mTor is an intracellular protein kinase implicated in the control of cellular proliferation in neoplastic cells. Treatment with RAD001 has been shown to inhibit these signalling events and leads to growth retardation of tumour cells. In addition RAD001 in vitro stops the formation and activity of osteoclasts. Therefore a therapy of advanced breast cancer with progressive bone metastases seems to be reasonable with RAD001. Recently promising data became available for the combination of RAD001 with endocrine treatments in the metastatic as well as the neoadjuvant setting.

  • Study Group: German Breast Group
  • Sponsor: GBG Forschungs GmbH
  • Study Chair: Prof. Dr. Nicolai Maass
  • Study Co-Chairs: Prof. Dr. Nadia Harbeck
  • Clinical Project Management: Konstantin Reißmüller
  • Datamanagement / Biometry: Dr. Valentina Nekljudova
  • Enrolment period: Q II 2006 - Q IV 2010
  • Proposed accrual: 130
←   ↑