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Fulvestrant +/- Akt Inhibition in Advanced Aromatase Inhibitor Resistant Breast Cancer (FAKTION)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01992952
Recruitment Status : Active, not recruiting
First Posted : November 25, 2013
Last Update Posted : August 10, 2022
Sponsor:
Collaborators:
AstraZeneca
Cenduit LLC
Covance
Cardiff and Vale University Health Board
Information provided by (Responsible Party):
Dr Margherita Carucci, Velindre NHS Trust

Study Description
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Brief Summary:

This is a two stage study, with an initial dose escalation phase I study and subsequent double blind randomised phase II controlled trial. Eligible patients are post-menopausal women with metastatic ER+ breast cancer not suitable for surgical resection. Patients should be suitable for endocrine treatment, but have received no more than 3 previous lines of endocrine treatment and up to 1 line of chemotherapy for metastatic disease. They will also have had progressive disease during treatment with an aromatase inhibitor. Following the dose-escalation in stage 1, patients will be randomised to receive fulvestrant plus either placebo or 480mg (or maximum tolerated dose) of AZD5363 oral capsules or tablets taken once daily.

Patients will receive fulvestrant in combination with either placebo or AZD5363 until disease progression. Patients may continue to receive fulvestrant and AZD5363/placebo treatment even after the last trial visit.


Condition or disease Intervention/treatment Phase
Estrogen Receptor Positive Breast Cancer Drug: AZD5363 Drug: Placebo Drug: Fulvestrant Phase 1 Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 149 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Randomised Placebo Controlled Trial of Fulvestrant +/- AZD5363 in Postmenopausal Women With Advanced Breast Cancer Previously Treated With a Third Generation Aromatase Inhibitor
Actual Study Start Date : May 2014
Actual Primary Completion Date : March 2019
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arms and Interventions
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Arm Intervention/treatment
Experimental: AZD5363 plus fulvestrant
Fulvestrant 500mg and AZD5363 4 days on 3 days off at dose determined in safety run in (maximum 480mg and minimum 320mg bd)
 Drug: AZD5363
Up to 480mg oral tablets twice a day, taken four days on, 3 days off treatment.

Drug: Fulvestrant
2 x 250mg injections, received on Days 1 and 15 of cycle 1, and on day 1 of each subsequent 28 day cycle.
Active Comparator: Placebo plus fulvestrant
Fulvestrant 500mg D1, D15 (cycle 1) and D1 of a 28 cycle thereafter. AZD5363 placebo 4 days on 3 days off
 Drug: Placebo
Placebo tablets taken twice a day, 4 days on treatment, 3 days off treatment

Drug: Fulvestrant
2 x 250mg injections, received on Days 1 and 15 of cycle 1, and on day 1 of each subsequent 28 day cycle.


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1b primary outcome measure: Maximum Tolerated Dose of AZD5363 in combination with fulvestrant [ Time Frame: 6 months ]
    To establish the MTD of AZD5363 in combination with fulvestrant and to establish a recommended phase 2 dose

  2. Phase 2 primary outcome: Progression free survival (PFS) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months after the last patient is randomised ]
    To establish the anti-tumour activity of the combination of AZD5363 with fulvestrant as measured by progression-free survival (PFS). This is the time from enrolment to any disease progression and/or any death, defined according to strict Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 criteria. Lesions will be compared to baseline measurements to assess progression.


Secondary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: Up to 12 months after the last patient is randomised ]
    To determine the number of patients reporting adverse events and to summarise the different types of adverse events experienced in each trial arm.

  2. Objective response rate [ Time Frame: Up to 12 months after the last patient is randomised ]
    The objective response rate will be used to determine the proportion of patients who responded to treatment.

  3. Overall survival [ Time Frame: Up to 12 months after the last patient is randomised ]
    The time from randomisation to death, with those still alive censored at date last seen

  4. The influence of mutational status of PIK3CA and the presence of complete loss of PTEN on outcome in the two treatment groups [ Time Frame: Up to 12 months after the last patient is randomised ]
    The mutational status of PIK3CA and the presence of complete loss of PTEN will be assessed at baseline.

  5. Fulvestrant pharmacokinetics [ Time Frame: Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 ]
    The minimum concentration (Cmin) of fulvestrant will be measured to determine whether AZD5363 affects the metabolism of fulvestrant.

  6. Number of patients requiring dose modifications [ Time Frame: Up to 12 months after the last patient is randomised ]
    The number of participants requiring dose modifications of AZD5363 and fulvestrant will be summarised for each trial arm. This will be broken down into the number of patients who withdraw from treatment and the number who were dose reduced while on treatment.


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

Inclusion Criteria:

  • Post-menopausal Women
  • Life expectancy 3 months
  • Histological confirmation of ER+ breast cancer
  • Clinical or histological confirmation of metastatic or locally advanced disease not amenable to surgical resection
  • Measurable or non-measurable disease
  • Adequate bone marrow, renal and hepatic function
  • Eastern Cooperative Oncology Group (ECOG) performance status < or equal to 2
  • Progressive disease whilst receiving an aromatase inhibitor (AI) for metastatic breast cancer (MBC)
  • Relapsed with metastatic disease whilst receiving an AI in adjuvant setting
  • Up to 3 prior lines of endocrine therapy for Advanced Breast Cancer
  • Up to 1 line of chemotherapy for Advanced Breast Cancer
  • Patient willing to donate archival tumour sample
  • Patient willing to donate baseline blood sample
  • Suitable for further endocrine therapy

Exclusion Criteria:

  • Previous treatment with fulvestrant or PI3K/mTOR(mammalian target of rapamycin )/Akt inhibitor therapy
  • Treatment with chemotherapy, immunotherapy or targeted, biologic or tumour embolisation within 21 days of study drug administration
  • Palliative radiotherapy within 7 days of study drug
  • Clinically significant abnormalities in glucose metabolism
  • Rapidly progressive visceral disease not suitable for further endocrine therapy
  • Known brain or leptomeningeal metastases
  • Any co-existing medical condition precluding trial entry including significant cardiac disease (to be defined in the protocol)
  • Concomitant medication unsuitable for combination with trial medication
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT01992952


Locations
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Sponsors and Collaborators
Velindre NHS Trust
AstraZeneca
Cenduit LLC
Covance
Cardiff and Vale University Health Board
Investigators
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Study Chair: Sacha Howell, FRCP PhD The University of Manchester and The Christie NHS Foundation Trust
Study Chair: Robert Jones, MRCP PhD Cardiff University and Velindre Cancer Centre
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Dr Margherita Carucci, Clinical Trial Manager, Velindre NHS Trust
ClinicalTrials.gov Identifier: NCT01992952    
Other Study ID Numbers: FAKTION
First Posted: November 25, 2013    Key Record Dates
Last Update Posted: August 10, 2022
Last Verified: August 2022
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
 Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs