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

NCT02127151 | Withdrawn Phase 2

• 2 other identifiers: UCL/13/00452013-003469-32
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) rate

  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 Outcomes (6)

• Best Response

  Up to 30 months

• Overall survival (OS)

  Up to 30 months

• Response at each radiological assessment

  Up to 30 months

• Duration of Response (DoR)

  Up to 30 months

• Median PFS

  Up to 30 months

Study Arms (1)

BMN 673

EXPERIMENTAL

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

Interventions

BMN 673 DRUG

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.

BMN 673

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College, London: lead
• Medivation, Inc.: collaborator

Study Sites (16)

Royal Sussex County Hospital

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, Greater Glasgow, G12 0YN, United Kingdom

Location

St Bartholomew's Hospital

London, Greater London, EC1A 7BE, United Kingdom

Location

University College Hospital

London, Greater London, NW1 2BU, United Kingdom

Location

The Christie Hospital

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Western General Hospital

Edinburgh, Lothian, EH4 2XU, United Kingdom

Location

The Churchill Hospital

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Velindre Cancer Centre

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

Location

St James's University Hospital

Leeds, South Yorkshire, LS9 7TF, United Kingdom

Location

Royal Marsden Hospital (Sutton)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

The Clatterbridge Cancer Centre

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

East Kent Hospitals University NHS Foundation Trust

Kent, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden Hospital (London and Surrey)

London and Surrey, United Kingdom

Location

Northern Centre for Cancer Care

Newcastle, NE7 7DN, United Kingdom

Location

Related Links

• Trial page on the University College London (UCL) Cancer Trials Centre website

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Rebecca Kristeleit

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 30, 2014
• Study Start: October 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: August 6, 2021

Record last verified: 2021-08

Locations

GB (16)