A Parp Inhibitor (BMN 673) for Inoperable Advanced eNDometrial cAncer (PANDA)

August 5, 2021 updated by: University College, London

A Single Arm Phase II Trial of BMN 673 for Inoperable, Advanced Endometrial Cancer With Retrospective PTEN, MSI and MRE11 Analysis

A Single Arm Phase II Trial of BMN 673 for Inoperable, Advanced Endometrial Cancer With Retrospective PTEN, MSI and MRE11 Analysis

PTEN= Phosphatase and tensin homolog MSI= Microsatellite instability MRE11= Double-strand break repair protein MRE11A

This trial will investigate whether the drug BMN 673 has therapeutic benefit in the treatment of advanced endometrial cancer. Nearly 8,000 patients are diagnosed with endometrial cancer in the UK every year. A significant proportion are either diagnosed with advanced disease which may be inoperable and/or metastatic (i.e spread to other organs outside the endometrium), or curable disease which relapses following first line treatment. There is no established standard of care for these patients as both chemo and hormone therapy has limited effectiveness and survival benefit. Survival rates have not improved in the past 20 years. Furthermore there are no so called 'targeted' drugs licensed for its treatment i.e. drugs that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. This leaves an unmet need for effective systemic treatments for advanced, inoperable and metastatic endometrial cancer.

BMN 673 has been shown to be potentially effective in treating cancers known to behave similarly to endometrial disease, both in the laboratory and in Phase I studies involving patients with advanced cancers. Similarly the drug appears to be relatively tolerable. A Phase II trial such as the one proposed by this application could demonstrate activity that might lead to a new effective treatment for patients with inoperable, advanced, recurrent or metastatic endometrial cancer, while the proposed substudy also presents the possibility of discovering a subset of patients more likely to derive benefit from BMN 673.

This trial is for adult women (18 and above) with advanced, inoperable or metastatic endometrial cancer. Patients will be recruited from approximately 15 National Health Service (NHS) Trusts based in the United Kingdom (UK). The study is expected to last approximately 18-24 months in terms of recruitment time, and a maximum of 100 eligible women will be registered. All patients will receive BMN 673 until their disease worsens or their doctor decides they should stop treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Bristol, United Kingdom, BS2 8ED
        • Bristol Haematology and Oncology Centre
      • Kent, United Kingdom
        • East Kent Hospitals University NHS Foundation Trust
      • London, United Kingdom, SE1 9RT
        • Guy's Hospital
      • London And Surrey, United Kingdom
        • The Royal Marsden Hospital (London and Surrey)
      • Newcastle, United Kingdom, NE7 7DN
        • Northern Centre for Cancer Care
    • East Sussex
      • Brighton, East Sussex, United Kingdom, BN2 5BE
        • Royal Sussex County Hospital
    • Greater Glasgow
      • Glasgow, Greater Glasgow, United Kingdom, G12 0YN
        • The Beatson West of Scotland Cancer Centre
    • Greater London
      • London, Greater London, United Kingdom, EC1A 7BE
        • St Bartholomew's Hospital
      • London, Greater London, United Kingdom, NW1 2BU
        • University College Hospital
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M20 4BX
        • The Christie Hospital
    • Lothian
      • Edinburgh, Lothian, United Kingdom, EH4 2XU
        • Western General Hospital
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • The Churchill Hospital
    • South Glamorgan
      • Cardiff, South Glamorgan, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
    • South Yorkshire
      • Leeds, South Yorkshire, United Kingdom, LS9 7TF
        • St James's University Hospital
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Royal Marsden Hospital (Sutton)
    • Wirral
      • Bebington, Wirral, United Kingdom, CH63 4JY
        • The Clatterbridge Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Histologically confirmed endometrial cancer. All histological subtypes except for carcinosarcoma are eligible
  • Evidence of inoperable, advanced, recurrent or metastatic disease by imaging and/or histological criteria
  • ≤ 1 previous line of systemic cancer therapy for inoperable, advanced, recurrent or metastatic endometrial cancer. Chemotherapy in the adjuvant setting is not considered a prior line of therapy unless recurrence occurred during adjuvant treatment or ≤ 6 months after the last treatment; first line treatment of advanced disease must include at least one cytotoxic agent to be considered as a line of therapy; prior hormonal treatment is not considered a line of therapy in any setting
  • Written informed consent obtained prior to any screening procedures
  • Patients must give consent for provision of archival histological tissue for the purposes of translational research. If archival tissue is not available or is of insufficient quantity and/or quality, the patient will have the option to consent to undergo biopsy where feasible. If biopsy is not feasible or the patient does not give consent for biopsy when archival tissue is not available, the patient will not be eligible for the trial. The quality and quantity of archival tissue will be assessed by a suitably qualified individual, usually a histopathologist, at site to ensure adequate tissue sample available for testing PTEN, MSI and MRE11
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
  • Life expectancy ≥ 12 weeks
  • Patient has at least one site of measurable disease on radiological imaging (i.e. target lesion) as per RECIST v1.1
  • Evidence of non-childbearing status and must not be lactating OR must have postmenopausal status
  • Adequate bone marrow and organ function

Exclusion Criteria:

  • Prior treatment with a poly adenosine diphosphate ribose polymerase (PARP) inhibitor
  • Progressive disease ≤ 3 months after platinum-based chemotherapy
  • Active uncontrolled infection including known Hepatitis B, Hepatitis C or HIV
  • Obstruction of the gastrointestinal tract or other reason preventing effective oral administration of medication
  • Serious concomitant non-malignant disease, uncontrolled organ dysfunction or medical disorder considered by the Investigator to make the subject unsuitable for trial participation including any psychiatric disorder that prevents informed consent
  • Significant active cardiovascular disease
  • Symptomatic brain metastases
  • Immunosuppressant therapy or considered to be otherwise immunocompromised
  • Myelodysplastic syndrome/acute myeloid leukaemia
  • Major surgery ≤ 28 days prior to registration, or ongoing clinically significant post-surgical complications
  • Chemotherapy, radiotherapy (a single fraction of palliative radiotherapy is allowed provided that the site being treated is not subsequently used as a target lesion as per RECIST v1.1 for the purpose of assessing tumour response on trial), immunotherapy or other investigational therapy for cancer ≤ 21 days prior to registration (42 days for nitrosoureas, mitomycin-C)
  • Unresolved clinically significant toxicities from prior systemic therapy
  • Known hypersensitivity to any of the agents or excipients to be administered
  • Unwillingness or inability to comply with the trial protocol
  • Patients with a history of other malignancy ≤ 3 years prior to registration with the exceptions of a) cone-biopsied in situ carcinoma of the cervix uteri; b) basal or squamous cell carcinoma of the skin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BMN 673
BMN 673 daily until progression, death, unacceptable toxicity, withdrawal of consent or any other criterion felt by the Investigator to preclude continuation of treatment.
Drug: BMN 673
Starting oral dose of 1.0 mg once daily to be taken until progression, death, unacceptable toxicity, withdrawal consent or any other criterion felt by the Investigator to preclude continuation of treatment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS) rate
Time Frame: 6 months
Measured from date of first BMN 673 dose to first progression (defined using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1) or death, whichever is the sooner.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to 30 months
Up to 30 months
Best Response
Time Frame: Up to 30 months
Measured from the date of first BMN 673 dose.
Up to 30 months
Response at each radiological assessment
Time Frame: Up to 30 months
Up to 30 months
Duration of Response (DoR)
Time Frame: Up to 30 months
Up to 30 months
Median PFS
Time Frame: Up to 30 months
Up to 30 months
Safety and toxicity
Time Frame: Up to 30 months
Common Terminology Criteria for Adverse Events (CTCAE) v4.03 grade 3-4 toxicity; dose reductions, omissions, delays; exposure; compliance.
Up to 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University College, London

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medivation, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rebecca Kristeleit, University College, London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 30, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 6, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UCL/13/0045
  • 2013-003469-32 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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