Prostate CancerPhase 1CaNCaP03NCT02324998
Study of Olaparib (± Degarelix) Given to Men With Intermediate/High Risk Prostate Cancer Before Prostatectomy
A Phase 1 study testing Olaparib and Degarelix in people with Prostate Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Despite recent advances in the treatment of Castrate-Resistant Prostate Cancer (CRPC), there remains an unmet medical need to identify and optimise additional treatment for those patients with early prostate cancer who are at greatest risk of relapse following first-line treatment with curative intent. Read more about this study
- Who is it for?
- Ages 18 to 73 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Olaparib and Degarelix
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2016to May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 73 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be included in the trial the patient must:
- Have given written informed consent to participate*
- Men aged 18 years or over
- Patients suitable for radical prostatectomy
- ECOG performance status of 0 or 1
- Access to archived diagnostic tissue or consent to undergo repeat biopsy, if necessary
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- Diagnosis of High risk or Intermediate risk prostate cancer, defined as:
- High risk disease: one or more of stage T2c - 3a, or PSA level >20ng/mL, or Gleason score ≥ 8
- Intermediate risk disease: two or more of: Stage T2 (any), PSA > 10, Gleason of ≥ 7
- Adequate bone marrow reserve and organ function (measured within 28 days prior to planned first olaparib administration) as demonstrated by the following values:
- Absolute neutrophil count ≥ 1.8 x 109/L
- Haemoglobin ≥ 117g/L
- Platelet count ≥ 135 x 109/L
- WBC ≥ 3.6 x 109/L
- Peripheral blood smear with no features of MDS/AML
- Adequate hepatic function:
- Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal (ULN) AND
- Total bilirubin ≤ 1.5 times the ULN unless in the presence of Gilbert's syndrome with an elevated indirect fraction
- Adequate renal function:
- Serum creatinine ≤ 1.5 times the ULN concurrent with creatinine clearance ≥ 50mL/min (calculated by Cockcroft and Gault equation)
- Willing to use two highly effective forms of contraception (see section 11.8) throughout their participation in the trial and for three months after their last dose of olaparib. Patients must refrain from donating sperm from the start of dosing up until sixteen weeks after discontinuing trial treatment
- Normal chest radiograph (CXR) and oxygen saturations
- Patients who are currently/have recently been involved in non-drug-based research are eligible to participate
- If the patient does not consent to participate in the optional genetic research (ctDNA studies on blood) or to optional additional biopsies there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the trial.
Who cannot join
- The presence of any of the following will preclude patient inclusion:
- Contraindication to olaparib or degarelix
- History of hypersensitivity to active or inactive excipients of olaparib
- Patients with known hypersensitivity to the degarelix active substance or mannitol must not receive degarelix.
- Current refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of olaparib
- As judged by the Investigator, any patient considered a poor medical risk due to a serious uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection including but not limited to:
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- Uncontrolled ventricular arrhythmia
- Recent myocardial infarction (within three months)
- Unstable spinal cord compression
- Superior vena cava syndrome
- Extensive bilateral lung disease on High Resolution Computed Tomography (HRCT)
- History of pneumonitis
- Active infection including hepatitis B, hepatitis C and Human Immunodeficiency Virus. Screening for chronic conditions is not required.
- Major surgery within 4 weeks prior to entry into the trial (excluding placement of vascular access). Patients must have recovered from side effects of any major surgery. Minor surgery (not including the diagnostic prostate biopsy) within 2 weeks prior to entry into the trial.
- Patients who have received (within last 3 months of trial entry) an investigational drug within a clinical trial will not be eligible to participate.
- Concomitant use of known potent CYP3A4 inhibitors and inducers. See section 10.4.1.1 for list and consider wash out periods.
- Blood transfusions within 1 month prior to the trial start
- ECG with mean resting QTc of ≥ 470ms (Fridericia; as per local reading) on two or more time points within a 24 hour period or family history of long QT syndrome
- Concomitant medications known to prolong the QT interval (see Appendix 1) or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age), History of Torsades de pointes.
- Judgement by the Investigator that the patient is unsuitable to participate in the trial and the patient is unlikely to comply with trial procedures, restrictions and requirements
- Patients with MDS or AML, or other previous malignancy except patients that have undergone treatment with curative intent for prior malignancy with no evidence of active prior malignancy are eligible.
- With the exception of alopecia, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE (version 4.03) Grade 1 at the time of starting olaparib treatment.
- Patients with a desire to have children following the trial will not be recruited
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Addenbrooke's Hospital, Cambridge University Hospitals Foundation Trust,
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: A Study Into the Pharmacodynamic Biomarker Effects of Olaparib (a PARP Inhibitor) ± Degarelix (a GnRH Antagonist) Given Prior to Radical Prostatectomy
Despite recent advances in the treatment of Castrate-Resistant Prostate Cancer (CRPC), there remains an unmet medical need to identify and optimise additional treatment for those patients with early prostate cancer who are at greatest risk of relapse following first-line treatment with curative intent.
This is a phase I study investigating the feasibility and tolerability of a short course of neoadjuvant treatment with olaparib, either as a monotherapy or in combination with degarelix) given in the window-of-opportunity prior to radical prostatectomy in men with early, localised intermediate-/high- risk prostate cancer. Our primary objective is to determine the pharmacodynamic biomarker effects of olaparib (a PARP inhibitor) in this patient population.
Read more
Participants will receive either single agent olaparib or olaparib in combination with degarelix (androgen deprivation) for two weeks prior to routine radical prostatectomy. We will use immunohistochemistry to quantify changes in the levels of biomarkers of PARP inhibition, e.g. PAR, gamma H2AX, pH2A(s129) and Rad51 foci, using tumour samples taken at baseline and at the time of radical prostatectomy. An intra-operative prostate biopsy will permit us to examine biomarker variability between the samples.
The incidence and severity of Adverse Events will be documented and we will assess the number of trial participants who undergo surgery on schedule. We will assess preliminary evidence of tumour response, e.g. pathological changes and Prostate Specific Antigen (PSA). We also intend to investigate changes to the ctDNA profile by comparing blood samples collected throughout the study.
- Conditions
- Prostate Cancer
- Being tested
- Olaparib, Degarelix
- Keywords
- Radical Prostatectomy, Prostate Cancer, PARP inhibition, Olaparib, Degarelix, Neoadjuvant, Pharmacodynamics, Pharmacokinetics, Biomarkers
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called AZD2281, Lynparza
PARP Inhibitor
DegarelixDrug
Also called Firmagon
Gonadotrophin releasing hormone blocker
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Olaparib Monotherapy Receives: Drug: Olaparib |
| Group B | Experimental | Olaparib in combination with degarelix Receives: Drug: Olaparib; Drug: Degarelix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of PARP Inhibition
Measure the degree of PARP inhibition by comparison of tumour samples taken from men with early prostate cancer at baseline and following treatment with olaparib (either alone or in combination with degarelix). Inhibition of PARP will be measured by the change in IHC levels of biomarkers such as PAR, gamma H2AX, pH2A(s129), Rad51 foci, FancD2 foci and ATM/ATR/CHK1/2.
Measured: Two week olaparib therapy (alone or in combination with degarelix)
Secondary outcomes (3)
Incidence and Severity of Adverse Events
Determine the incidence and severity of adverse events caused by treatment for 14 days with olaparib (either alone or in combination with degarelix) prior to radical prostatectomy. The severity of adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.03).
Measured: Two week olaparib therapy (alone or in combination with degarelix)
Feasibility of treatment approach
Assess the number of patients who undergo radical prostatectomy on schedule after 14 days of treatment with olaparib (either alone or in combination with degarelix).
Measured: Two week olaparib therapy (alone or in combination with degarelix)
Clinical benefit rate
To assess preliminary evidence of tumour response, e.g. pathological changes and Prostrate Specific Antigen (PSA) levels, following 14 days treatment with olaparib (±degarelix).
Measured: Two week olaparib therapy (alone or in combination with degarelix)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2014 (estimated)
- Study startDec 2016
- Primary completionMay 2019
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Simon C Pacey, MRCP, Ph.D, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02324998
- Sponsor's protocol ID
- CaNCaP03
- Other IDs
- 2014-004417-86, 2014
- Acronym
- CaNCaP03
- Status last verified
- Aug 2019
- First submitted
- 19 Dec 2014
- Last updated
- 29 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study Into the Pharmacodynamic Biomarker Effects of Olaparib (a PARP Inhibitor) ± Degarelix (a GnRH Antagonist) Given Prior to Radical Prostatectomy
- ClinicalTrials.gov ID
- NCT02324998
- Acronym / sponsor ID
- CaNCaP03 / CaNCaP03
- Conditions
- Prostate Cancer
- Keywords
- Radical Prostatectomy, Prostate Cancer, PARP inhibition, Olaparib, Degarelix, Neoadjuvant, Pharmacodynamics, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Dec 2016
- Primary completion
- May 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 24 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite recent advances in the treatment of Castrate-Resistant Prostate Cancer (CRPC), there remains an unmet medical need to identify and optimise additional treatment for those patients with early prostate cancer who are at greatest risk of relapse following first-line treatment with curative intent.
This is a phase I study investigating the feasibility and tolerability of a short course of neoadjuvant treatment with olaparib, either as a monotherapy or in combination with degarelix) given in the window-of-opportunity prior to radical prostatectomy in men with early, localised intermediate-/high- risk prostate cancer. Our primary objective is to determine the pharmacodynamic biomarker effects of olaparib (a PARP inhibitor) in this patient population.
Participants will receive either single agent olaparib or olaparib in combination with degarelix (androgen deprivation) for two weeks prior to routine radical prostatectomy. We will use immunohistochemistry to quantify changes in the levels of biomarkers of PARP inhibition, e.g. PAR, gamma H2AX, pH2A(s129) and Rad51 foci, using tumour samples taken at baseline and at the time of radical prostatectomy. An intra-operative prostate biopsy will permit us to examine biomarker variability between the samples.
The incidence and severity of Adverse Events will be documented and we will assess the number of trial participants who undergo surgery on schedule. We will assess preliminary evidence of tumour response, e.g. pathological changes and Prostate Specific Antigen (PSA). We also intend to investigate changes to the ctDNA profile by comparing blood samples collected throughout the study.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: OlaparibOlaparib Monotherapy |
| Group B | Experimental | Drug: Olaparib, Drug: DegarelixOlaparib in combination with degarelix |
Who may qualify
- Ages
- 18 to 73 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Have given written informed consent to participate*
- Men aged 18 years or over
- Patients suitable for radical prostatectomy
- ECOG performance status of 0 or 1
- Access to archived diagnostic tissue or consent to undergo repeat biopsy, if necessary
Key exclusion criteria (23 listed)
- Contraindication to olaparib or degarelix
- History of hypersensitivity to active or inactive excipients of olaparib
- Patients with known hypersensitivity to the degarelix active substance or mannitol must not receive degarelix.
- Current refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of olaparib
- As judged by the Investigator, any patient considered a poor medical risk due to a serious uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection including but not limited to:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibAlso: AZD2281, LynparzaPARP Inhibitor | Drug | Group A, Group B |
| DegarelixAlso: FirmagonGonadotrophin releasing hormone blocker | Drug | Group B |
Primary outcome
Determination of PARP Inhibition
Time frame: Two week olaparib therapy (alone or in combination with degarelix)
Measure the degree of PARP inhibition by comparison of tumour samples taken from men with early prostate cancer at baseline and following treatment with olaparib (either alone or in combination with degarelix). Inhibition of PARP will be measured by the change in IHC levels of biomarkers such as PAR, gamma H2AX, pH2A(s129), Rad51 foci, FancD2 foci and ATM/ATR/CHK1/2.
3 secondary outcomes
Incidence and Severity of Adverse Events
Time frame: Two week olaparib therapy (alone or in combination with degarelix)
Feasibility of treatment approach
Time frame: Two week olaparib therapy (alone or in combination with degarelix)
Clinical benefit rate
Time frame: Two week olaparib therapy (alone or in combination with degarelix)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simon C Pacey, MRCP, Ph.D principal investigator
University of Cambridge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaparib and Degarelix in people with Prostate Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of PARP Inhibition (time frame: Two week olaparib therapy (alone or in combination with degarelix)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2019.