Study to Determine the Feasibility, Evaluability and Variability in Markers of Drug Action in Castration Resistant Prostate Cancer (BIOMETHS)

July 25, 2016 updated by: Safia Barber, The Christie NHS Foundation Trust

BIOMETHS Study. A Methodology Study to Determine the Feasibility, Evaluability and Temporal Variability in Candidate Pharmacodynamic Markers of Drug Action in Castration Resistant Prostate Cancer

This is a biopsy feasibility study in which patients with castration resistant prostate cancer (CRPC) will be asked to donate primary and metastatic tumour tissue (both archival and de novo), blood samples, a urine specimen and clinical data for research.

Study Overview

Status

Status

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

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.

Detailed Description

The study aims to determine the feasibility of sampling and evaluability of biomarkers in CRPC tissue samples and circulating tumour cells (CTCs). Exploratory biomarker analysis may include, but will not be limited to, understanding the potential proof of mechanism (POM), proof of principle (POP) or predictive biomarkers of response to potential therapeutic agents for CRPC patients, or factors that may influence the development of CRPC.

This study is predicated on the continued development of agents targeting the PI3K pathway such as AZD(AstraZeneca Drug)8186 (PI3Kb); AZD5363 (Akt) and AZD2014 (mTOR) and anti-hormonals which are expected to deliver benefit in the management of tumours dependent on PI3K signalling as a result of e.g. phosphatase and tensin homolog (PTEN) deficiency or androgen receptor activation.

Loss of PTEN is common in CRPC. Current data indicate that AZD8186 inhibits PI3K downstream signalling in PTEN deficient but not in PTEN proficient cells and hence POM and efficacy will need to be determined in tumours with PTEN protein loss. In future studies, paired biopsy tumour tissue will be accessible for assessment of POM and PTEN status, either bone metastases lymph node metastases, or within the prostate tumour.

Recruitment of patients will be carried out in two stages as follows:

Stage 1 The first 10 eligible and consenting patients will be enrolled in the study and will undergo sequential biopsies. For all stage one participants, the PTEN status will be retrospectively determined from archival tumour samples by immuno-histochemistry (IHC).

The results of the PTEN analysis from Stage 1, will determine the number of patients in Stage 2 that must be PTEN positive or PTEN null. For this study the intent is to have equal numbers of each type i.e. ten PTEN positive and ten PTEN null.

Stage 2

In Stage 2, patients will be asked to sign a pre-screening consent form for their archival tumour sample to be analysed for PTEN status prior to undergoing any main study screening procedures. If their PTEN status matches one of the available slots they will be enrolled into the study.

Once a cohort reaches ten PTEN positive and ten PTEN null patients, it will close to recruitment.

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.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

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
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust

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

Male

Sampling Method

Non-Probability Sample

Study Population

Males (18+) with metastatic hormone refractory prostate cancer

Description

Inclusion Criteria:

  • Patients with metastatic prostate cancer post maximal androgen blockade (MAB) with primary or metastatic cancer deposits amenable to biopsy
  • Patients aged 18 years and older
  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • World Health Organisation (WHO) performance status 0 to 2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
  • Provision of archival tumour sample for PTEN status determination as directs group assignment
  • Provision of written informed consent
  • Provision of cancer tissue samples, willing to undergo 1-3 biopsies on 2 separate occasions
  • No change of cancer treatment anticipated until final biopsy/ blood samples have been taken
  • Serum testosterone level <50 ng/dL sustained by medical or surgical castration

Exclusion Criteria:

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous enrolment in the present study
  • As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
  • Evidence of any other significant clinical disorder or laboratory finding that made it undesirable for the patient to participate in the study
  • Any investigational agents or study drugs from a previous clinical study within 30 days of the first tissue collection
  • Radiotherapy to lesion to be biopsied within 4 weeks of biopsy
  • Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
  • Patients at increased risk of bleeding as a result of biopsy
  • History of bleeding disorders or thrombocytopenia (platelets <100)
  • Concomitant treatment with anticoagulant therapy such as warfarin/low molecular weight heparin (Aspirin not contra-indicated but consider temporary cessation if biopsy site has higher risk of bleeding e.g. liver)
  • Current urinary tract infection (UTI) or prostatitis
  • Known infection with HIV, Hepatitis B or Hepatitis C

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.
Metastatic CRPC
Patients with metastatic prostate cancer post maximal androgen blockade (MAB) with primary or metastatic cancer deposits amenable to biopsy. Patients will have biopsies, blood and urine samples taken.
Procedure: Biopsies, blood and urine samples

Session 1: Biopsies will be taken from the main study lesion and up to 2 metastatic sites at 1 visit or over 3 visits. Both formalin fixed and snap frozen material will be collected. At the session (i.e. once over the potential maximum of 3 visits in a session) a urine sample, blood samples for circulating tumour cells (CTC) and an exploratory blood sample (processed to plasma) will be taken.

Session 2: 7 days +/-3 following the last biopsy taken from Session 1, repeat biopsies from the same tumour sites will be obtained. In cases where this is not possible, it is acceptable to biopsy alternative lesions. As in Session 1 biopsies may be taken at 1 visit or over 3 visits and urine, CTC blood samples and an exploratory blood sample (processed to plasma) will be taken.

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
Time Frame
Percentage of formalin fixed cancer tissue samples evaluable for immunohistochemical analysis
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Baseline levels of biomarkers in formalin fixed cancer tissue samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Intra-lesion temporal variability between formalin fixed cancer tissue samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Intra-lesion spatial variability between formalin fixed cancer tissue samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)

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
Time Frame
Percentage of frozen cancer tissue samples evaluable for biomarker analysis
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Baseline levels of biomarkers in frozen cancer tissue samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Intra-lesion temporal variability between frozen cancer tissue samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Intra-lesion spatial variability between frozen cancer tissue samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Intra-patient, inter-lesion variability (where possible) between samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
Percentage concordance between biomarker measurements on circulating tumour cells (CTCs) and tumour samples
Time Frame: Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)
(1 to 3 visits)
Samples taken in session 1 (1 to 3 visits) and then 7 days +/- 3 days at session 2 (1 to 3 visits)

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.
The Christie NHS Foundation Trust

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.
AstraZeneca

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.
  • Study Chair: Tony Elliott, The Christie NHS Foundation Trust

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

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.
December 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.
July 1, 2016

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.
July 1, 2016

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 16, 2015

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 20, 2015

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 23, 2015

Study Record Updates

Last Update Posted (Estimate)

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.
July 26, 2016

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.
July 25, 2016

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.
July 1, 2016

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.
  • CFTSp063 / 12_DOG04_145

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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