Clinical Trials /

AZD4547 & Anastrozole or Letrozole (NSAIs) in ER+ Breast Cancer Patients Who Have Progressed on NSAIs (RADICAL)

NCT01791985

Description:

This study is looking at a new drug called AZD4547 which is being tested for the treatment of oestrogen receptor positive breast cancer. AZD4547 is a drug which specifically "blocks" proteins called fibroblast growth factor receptors (FGFR1) that are involved in the processes that help cancer cells to grow. These proteins may also be responsible for the development of resistance to hormonal therapies used to treat some breast cancers. AZD4547 is not yet approved for use in breast cancer and is therefore being used in this study as a research drug. The investigators will also test the theory that it is not necessary for high levels of FGFR1 to be present in the body to see benefit from AZD4547. (Stage 1 only)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AZD4547 & Anastrozole or Letrozole (NSAIs) in ER+ Breast Cancer Patients Who Have Progressed on NSAIs (RADICAL)
  • Official Title: A Single Arm Phase IIa Study (With Combination SRI) to Assess the Safety & Efficacy of AZD4547 in Combination With Either Anastrozole or Letrozole in ER+ Breast Cancer Patients Who Have Progressed on Treatment With Anastrozole or Letrozole

Clinical Trial IDs

  • ORG STUDY ID: C/23/2011
  • SECONDARY ID: 2011-000454-32
  • NCT ID: NCT01791985

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
AZD4547 / anastrozole or letrozoleSingle arm study

Purpose

This study is looking at a new drug called AZD4547 which is being tested for the treatment of oestrogen receptor positive breast cancer. AZD4547 is a drug which specifically "blocks" proteins called fibroblast growth factor receptors (FGFR1) that are involved in the processes that help cancer cells to grow. These proteins may also be responsible for the development of resistance to hormonal therapies used to treat some breast cancers. AZD4547 is not yet approved for use in breast cancer and is therefore being used in this study as a research drug. The investigators will also test the theory that it is not necessary for high levels of FGFR1 to be present in the body to see benefit from AZD4547. (Stage 1 only)

Detailed Description

      The study will be carried out in two stages. Stage 1 is to find a suitable dose of AZD4547
      which can be used together with a class of drugs called nonsteroidal aromatase inhibitors
      (e.g. anastrozole or letrozole) i.e. a dose which does not cause too many unacceptable side
      effects.

      Patients with hormone sensitive (oestrogen receptor positive) breast cancer, whose current
      treatment with anastrozole or letrozole has recently stopped working properly will be
      eligible for this stage.

      Stage 2 will then assess the efficacy of AZD4547, based on the change in tumour size at 12
      weeks (or progression if prior to week 12), when used in combination with either anastrozole
      or letrozole in patients with hormone sensitive (oestrogen receptor positive) breast cancer,
      who have progressed on treatment with either anastrozole or letrozole in any setting.

      In both stages, the study will look at how well the new treatment is tolerated.

      Each patient is only allowed to take part in either stage 1 or 2.

      The study will be run in 9 Hospitals across England and Scotland.
    

Trial Arms

NameTypeDescriptionInterventions
Single arm studyExperimentalNSAI (anastrozole (1mg) or letrozole (2.5mg)), orally, once daily but together with twice daily AZD4547 (80mg). AZD4547 will be given on an intermittent schedule of one week on / one week off.
  • AZD4547 / anastrozole or letrozole

Eligibility Criteria

        Main Eligibility Criteria

          -  Written informed consent and ability to comply with study protocol

          -  Aged ≥ 25 years of age

          -  Post menopausal women with histological confirmation of breast cancer with documented
             positive oestrogen receptor status (ER+) of primary or metastatic tumour tissue

          -  ECOG performance status 0-1 and minimum life expectancy of 12 weeks

          -  Fulfils criteria for previous treatment of breast cancer:

          -  Safety run-in: Relapse during a single regimen of adjuvant endocrine therapy with
             either anastrozole or letrozole or

          -  Progression during first line endocrine therapy with anastrozole or letrozole for
             advanced breast cancer Phase IIa: Progressing or progression at some point during
             breast cancer treatment on endocrine therapy with a non-steroidal AI*
             Co-administration of a targeted agent with the non-steroidal AI is permitted providing
             all toxicities have recovered to CTCAE Grade 1 or below.

          -  Prior chemotherapy in the advanced and adjuvant setting is permitted.

          -  Prior treatment with exemestane with or without everolimus is permitted.

             *anastrozole or letrozole does not have to be the most recent therapy

          -  Safety run-in: At least 1 lesion (measurable/non measurable) that can be accurately
             assessed by CT/MRI/plain x-ray at baseline and follow-up Phase IIa: At least 1
             measurable lesion ≥ 10mm in longest diameter (or ≥ 15mm in the short axis for nodal
             disease) at baseline that can be accurately assessed by CT/MRI at baseline and follow
             up. Patients with bone only metastatic cancer must have a lytic or mixed lytic-blastic
             lesion that can be accurately assessed by CT or MRI.

          -  Adequate haematological, hepatic and renal function

          -  Phase IIa: Mandatory provision of tumour biopsy for assessment of oncology biomarkers

          -  Safety run-in: Study entry must be preceded by a minimum of 21 days of anastrozole or
             letrozole treatment

          -  Phase IIa: No restriction to duration of anastrozole or letrozole treatment prior to
             study entry.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:25 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of AZD4547 to be used in combination with a standard dose of anastrozole or letrozole, as assessed by Dose limiting toxicity
Time Frame:DLT assessment window - days 1 to 28 of cycle 1
Safety Issue:
Description:This is the primary outcome measure in the Safety Run-In part of the study

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Imperial College London

Trial Keywords

  • Breast Cancer
  • AZD4547
  • Safety Run-In
  • FGFR1
  • ER positive breast cancer
  • Single arm phase IIa study

Last Updated

April 4, 2017