Prostate CancerPhase 1/2NCT02049190
Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer
A Phase 1/2 study testing onapristone and abiraterone in people with Prostate Cancer and Metastatic Prostate Cancer, run by Arno Therapeutics at 1 site in United Kingdom.
Trial summary
This is an open-label, randomized, parallel group two-stage phase 1-2 study with an escalation and an expansion component. This study will evaluate an extended-release (ER) formulation of onapristone in patients with prostate cancer in which Progesterone Receptor (PR) may be contributing to tumor progression. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Metastatic Prostate Cancer, Androgen-independent Prostate Cancer
- What is being tested?
- onapristone and abiraterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2014to Dec 2017
- Phase
- Phase 1/2
- 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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male patients, 18 years of age or greater;
- Histologically confirmed adenocarcinoma of the prostate (without neuroendocrine differentiation or small cell features);
- In Stage 2, a mandatory biopsy is required with confirmed PR or APR in ≥1% tumor cells. For patients recruited to the abiraterone-onapristone combination arm, the biopsy must be performed on abiraterone administered as the most recent treatment and after a minimum of 2 weeks continuous treatment. For other patients, the biopsy must be taken at progression on or after abiraterone or enzalutamide or before screening with no anti-cancer treatment taken in the intervening period and a maximum of six (6) months prior to study start. If archival tissue is also available this should be provided for comparison purposes; a paired biopsy at day 8-28 is optional;
- Metastatic or recurrent inoperable disease after previous surgery, radiation therapy, and/or chemotherapy;
- For patients in Stage 1 and for patients in Stage 2 who will receive combination therapy with onapristone and abiraterone: no more than one prior chemotherapy regimen for CRPC (docetaxel rechallenge will be regarded as one line of chemotherapy); for patients in Stage 2 who will receive onapristone monotherapy: no prior chemotherapy is allowed;
- Disease that has progressed by PSA or radiologically, on abiraterone or enzalutamide. Disease progression for study entry is defined as one or both of:
Show all 19Show fewer
- PSA progression defined by a minimum of two rising PSA levels with an interval of ≥1 week between each determination.
- Radiological progression per RECIST 1.1;
- For patients recruited to the abiraterone-onapristone combination arm, progression on abiraterone as their last line of treatment is required after a prior response to abiraterone;
- The PSA value at screening and baseline should be ≥ 2 µg/L (2 ng/mL);
- For onapristone monotherapy, corticosteroid discontinuation >4 weeks or >2 weeks with normal adrenal function confirmed by an ACTH stimulation test. For the combination onapristone - abiraterone arm, prednisolone 5mg BID and no other steroid regimen allowed for 2 weeks prior to treatment initiation;
- Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration);
- For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial;
- Serum testosterone level < 1.7 nmol/L (50 ng/dL);
- Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks;
- Evaluable disease per RECIST 1.1 [Eisenhauer 2009] or Prostate Cancer Clinical Trials Working Group 2 (PCWG2) [Scher 2008];
- ECOG performance status 0-2;
- Life expectancy ≥ 3 months;
- Willing and able to sign written informed consent per ICH-GCP, the local regulatory requirements, and local data protection laws prior to study-specific screening procedures.
Who cannot join
- Serum creatinine >1.5 ULN;
- On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities;
- Liver function tests documented within the screening period and/or at baseline:
- Total bilirubin > ULN (except in patients diagnosed with Gilbert's disease);
- Alkaline phosphatase > 2.5 x UNL, unless test for alkaline phosphatase isoenzymes is elevated only for bone isoenzyme;
- ALT/AST > UNL or > 2.5 x UNL in case of liver metastases;
Show all 35Show fewer
- Absolute neutrophil count < 1,500/µL, platelet count < 100,000/µL, and hemoglobin < 5.6 mmol/L (9 g/dL) and no growth factors or blood transfusions within 7 days of these values;
- Serum albumin < 25 g/L (2.5 g/dL);
- Known positive virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B (surface antigen), or hepatitis C (testing not required);
- Chronic inflammatory liver condition. History or clinical evidence of any liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia;
- Patients with any other prior malignancy are not allowed except for:
- Adequately treated basal cell or squamous cell skin cancer;
- Adequately treated Stage I or II cancer from which the patient is currently in complete remission;
- Other cancer from which the patient has been disease-free for 2 years;
- For Stage 1 only: Chronic adrenal failure or is receiving concurrent long-term corticosteroid therapy. Prior long-term corticosteroids must be stopped ≥4 weeks or >2 weeks if normal adrenal function is confirmed by an ACTH stimulation test prior to start of study drug;
- History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating; e.g., active or clinically significant history of disease involving a major organ system-vascular, cardiac, uncontrolled hypertension, pulmonary, gastrointestinal, hematologic, neurologic, neoplastic, renal, endocrine or immunodeficiency, or clinically significant active psychiatric disorders;
- Used any prescription medication during the prior 2 weeks that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4 (see Appendix 4);
- Received an investigational product or been treated with an investigational device within 30 days prior to first drug administration, or plans to start any other investigational product or device study within 30 days after last drug administration;
- Received prior therapies within the following time period prior to receipt of first dose of study drug (Day 1, without withdrawal response and with no plans to initiate any of these during study:
- Ketoconazole or bicalutamide within 6 weeks;
- Systemic hormone therapy, chemotherapy, targeted therapies, antibodies within 4 weeks excluding abiraterone in the abiraterone-onapristone combination arm;
- Fractionated radiotherapy within 3 weeks;
- Single fraction of radiotherapy within 2 weeks;
- Radionuclide therapy within 8 weeks;
- Brachytherapy Pd-103 implant within the last 3 months;
- Brachytherapy I-125 implants within 12 months.
- Concurrent use of herbal products that may decrease PSA levels (e.g., saw palmetto);
- Residual toxicity of prior anticancer treatment > grade 1 except for alopecia;
- Brain metastases, active epidural disease or spinal cord compression, unless treated at least 4 weeks before entry, and stable with steroid treatment for ≥1 week;
- Paget's disease of the bone;
- Structurally unstable bone lesions suggesting impending fracture;
- Patients with reproductive potential not employing adequate contraception during treatment and for 1 month after completing treatment;
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to swallow pills;
- Mental incapacity or language barriers precluding adequate understanding, co-operation, and compliance with the study requirements;
- Is, in the judgment of the investigator, unable or unwilling to comply with the requirements of the study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Inst of Cancer Research & Royal Marsden NHS Foundation Trust
Sutton Surrey, SH2 5NG
Gerhardt Attard, MD, PhD, MRCP, (+44) 020 872224137, gerhardt.attard@icr.ac.uk
Johann S De Bono, MD, PhD, MSc, FRCP
About this study
Official title: A Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer
This is an open-label, randomized, parallel group two-stage phase 1-2 study with an escalation and an expansion component. This study will evaluate an extended-release (ER) formulation of onapristone in patients with prostate cancer in which Progesterone Receptor (PR) may be contributing to tumor progression. A companion diagnostic to select patients whose prostate cancer expresses the activated form of the PR (APR) is under development and will be implemented in this study; it may be used to further enrich the selection of the population based upon ongoing review of the results. Patients will be treated until occurrence of an intolerable safety issue, treatment failure, if patient elects to withdraw, or for non-compliance with either protocol-specified evaluations or onapristone treatment. An additional cohort of patients will be included at the recommended phase 2 dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.
- Conditions
- Prostate Cancer, Metastatic Prostate Cancer, Androgen-independent Prostate Cancer, Recurrent Prostate Cancer
- Being tested
- onapristone, abiraterone
- Keywords
- Advanced Prostate Cancer, Castration-resistant Prostate Cancer, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Genital Diseases, Male, Prostatic Diseases, onapristone
- Medical subject headings
- Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Genital Diseases, Male, Prostatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
onapristoneDrug
Also called ZK 98299
abirateroneDrug
Also called Zytiga
| Study group | Role | What they receive |
|---|---|---|
| onapristone 10 mg BID | Experimental | onapristone 10 mg BID extended-release tablets Receives: Drug: onapristone |
| onapristone 20 mg BID | Experimental | onapristone 20 mg BID extended-release tablets Receives: Drug: onapristone |
| onapristone 30 mg BID | Experimental | onapristone 30 mg BID extended-release tablets Receives: Drug: onapristone |
| onapristone 40 mg BID | Experimental | onapristone 40 mg BID extended-release tablets Receives: Drug: onapristone |
| onapristone 50 mg BID | Experimental | onapristone 50 mg BID extended-release Receives: Drug: onapristone |
| onapristone 30 mg BID + abiraterone 1000 mg | Experimental | Expansion cohort: onapristone 30 mg BID + abiraterone 1000 mg Receives: Drug: onapristone; Drug: abiraterone |
| onapristone 50 mg BID + abiraterone 1000 mg | Experimental | Expansion cohort: onapristone 50 mg BID + abiraterone 1000 mg Receives: Drug: onapristone; Drug: abiraterone |
| Expansion cohort: onapristone 50 mg BID | Experimental | Expansion cohort: onapristone 50 mg BID Receives: Drug: onapristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities related to onapristone or the combination of onapristone and abiraterone utilizing a day 57 safety cut off and based on CTCAE v4
Measured: Baseline to 57 days post-first dose
Response to onapristone or the combination of onapristone and abiraterone
- Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart and / or
- PSA decline of ≥ 50% (according to the PCWG2).
Measured: Baseline to 30 Days after last dose
Secondary outcomes (2)
Safety and tolerability of extended-release onapristone tablets BID
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and changes in PSA and other clinical laboratory values.
Measured: Baseline to 30 Days after last dose
PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine
Measured: Baseline to 30 Days after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionJul 2017 (estimated)
- Study completionDec 2017 (estimated)
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arno Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02049190
- Sponsor's protocol ID
- ARN-AR18-CT-102
- Status last verified
- Jun 2015
- First submitted
- 28 Jan 2014
- Last updated
- 24 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02049190
- Acronym / sponsor ID
- ARN-AR18-CT-102
- Conditions
- Prostate Cancer, Metastatic Prostate Cancer, Androgen-independent Prostate Cancer, Recurrent Prostate Cancer
- Keywords
- Advanced Prostate Cancer, Castration-resistant Prostate Cancer, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Genital Diseases, Male
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Arno TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 30 Jan 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.
This is an open-label, randomized, parallel group two-stage phase 1-2 study with an escalation and an expansion component. This study will evaluate an extended-release (ER) formulation of onapristone in patients with prostate cancer in which Progesterone Receptor (PR) may be contributing to tumor progression. A companion diagnostic to select patients whose prostate cancer expresses the activated form of the PR (APR) is under development and will be implemented in this study; it may be used to further enrich the selection of the population based upon ongoing review of the results. Patients will be treated until occurrence of an intolerable safety issue, treatment failure, if patient elects to withdraw, or for non-compliance with either protocol-specified evaluations or onapristone treatment. An additional cohort of patients will be included at the recommended phase 2 dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| onapristone 10 mg BID | Experimental | Drug: onapristoneonapristone 10 mg BID extended-release tablets |
| onapristone 20 mg BID | Experimental | Drug: onapristoneonapristone 20 mg BID extended-release tablets |
| onapristone 30 mg BID | Experimental | Drug: onapristoneonapristone 30 mg BID extended-release tablets |
| onapristone 40 mg BID | Experimental | Drug: onapristoneonapristone 40 mg BID extended-release tablets |
| onapristone 50 mg BID | Experimental | Drug: onapristoneonapristone 50 mg BID extended-release |
| onapristone 30 mg BID + abiraterone 1000 mg | Experimental | Drug: onapristone, Drug: abirateroneExpansion cohort: onapristone 30 mg BID + abiraterone 1000 mg |
| onapristone 50 mg BID + abiraterone 1000 mg | Experimental | Drug: onapristone, Drug: abirateroneExpansion cohort: onapristone 50 mg BID + abiraterone 1000 mg |
| Expansion cohort: onapristone 50 mg BID | Experimental | Drug: onapristoneExpansion cohort: onapristone 50 mg BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Male patients, 18 years of age or greater;
- Histologically confirmed adenocarcinoma of the prostate (without neuroendocrine differentiation or small cell features);
- In Stage 2, a mandatory biopsy is required with confirmed PR or APR in ≥1% tumor cells. For patients recruited to the abiraterone-onapristone combination arm, the biopsy must be performed on abiraterone administered as the most recent treatment and after a minimum of 2 weeks continuous treatment. For other patients, the biopsy must be taken at progression on or after abiraterone or enzalutamide or before screening with no anti-cancer treatment taken in the intervening period and a maximum of six (6) months prior to study start. If archival tissue is also available this should be provided for comparison purposes; a paired biopsy at day 8-28 is optional;
- Metastatic or recurrent inoperable disease after previous surgery, radiation therapy, and/or chemotherapy;
- For patients in Stage 1 and for patients in Stage 2 who will receive combination therapy with onapristone and abiraterone: no more than one prior chemotherapy regimen for CRPC (docetaxel rechallenge will be regarded as one line of chemotherapy); for patients in Stage 2 who will receive onapristone monotherapy: no prior chemotherapy is allowed;
Key exclusion criteria (35 listed)
- Serum creatinine >1.5 ULN;
- On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities;
- Liver function tests documented within the screening period and/or at baseline:
- Absolute neutrophil count < 1,500/µL, platelet count < 100,000/µL, and hemoglobin < 5.6 mmol/L (9 g/dL) and no growth factors or blood transfusions within 7 days of these values;
- Serum albumin < 25 g/L (2.5 g/dL);
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 |
|---|---|---|
| onapristoneAlso: ZK 98299 | Drug | Expansion cohort: onapristone 50 mg BID, onapristone 10 mg BID, onapristone 20 mg BID, onapristone 30 mg BID, onapristone 30 mg BID + abiraterone 1000 mg, onapristone 40 mg BID, onapristone 50 mg BID, onapristone 50 mg BID + abiraterone 1000 mg |
| abirateroneAlso: Zytiga | Drug | onapristone 30 mg BID + abiraterone 1000 mg, onapristone 50 mg BID + abiraterone 1000 mg |
Primary outcome
Dose limiting toxicities related to onapristone or the combination of onapristone and abiraterone utilizing a day 57 safety cut off and based on CTCAE v4
Time frame: Baseline to 57 days post-first dose
Response to onapristone or the combination of onapristone and abiraterone
Time frame: Baseline to 30 Days after last dose
* Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart and / or * PSA decline of ≥ 50% (according to the PCWG2).
2 secondary outcomes
Safety and tolerability of extended-release onapristone tablets BID
Time frame: Baseline to 30 Days after last dose
PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine
Time frame: Baseline to 30 Days after last dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2015.
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing onapristone and abiraterone in people with Prostate Cancer and Metastatic Prostate Cancer, run by Arno Therapeutics 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 19 inclusion and 35 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: status not confirmed, as of the sponsor's last update on 24 Jun 2015. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alice S Bexon, MD (1-617-417-7300, alice.bexon@bexonclinical.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities related to onapristone or the combination of onapristone and abiraterone utilizing a day 57 safety cut off and based on CTCAE v4 (time frame: Baseline to 57 days post-first dose). The study lists 2 primary outcomes in all. 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 24 Jun 2015.