Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone TherapyPhase 1/2NCT02052128
Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers
A Phase 1/2 study testing onapristone in people with Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy, run by Arno Therapeutics at 3 sites in France.
Trial summary
This is a multi-center, open-label, randomized, parallel group two-stage phase 1 study with a phase 2 expansion component in pts with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy
- What is being tested?
- onapristone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesFrance
- Study dates
- Jan 2014to Apr 2016
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Post- menopausal female patients, 18 years of age or greater.
- In Stage 1, recurrent or metastatic PR-expressing cancer that has the potential to benefit from an anti-progestin treatment including but not limited to endometrial cancer, ovarian, or breast cancer or uterine sarcoma. In Stage 2, recurrent or metastatic PR-expression uterine endometrioid adenocarcinoma that is determined to be APRpos.
- Patients who have metastatic or recurrent disease after previous surgery, radiation therapy, and/or chemotherapy are eligible. In Stage 1, no restriction is placed on the number of prior therapies. In Stage 2, patients may have 0 or 1 prior chemotherapy treatments for adjuvant or metastatic disease and no prior endocrine therapies.
- In Stage 1, evaluable disease per RECIST 1.1. In Stage 2, measurable disease.
- Appropriate archival OR current tissue blocks or biopsy specimens to determine ER/PR and APR status.
- Signed, written informed consent must be obtained and documented according to ICH-GCP, the local regulatory requirements, and local data protection laws prior to study-specific screening procedures.
- ECOG performance status 0-1.
- Health care coverage.
Who cannot join
- Calculated creatinine clearance of <60 mL/min in Stage 1 and <40 mL/min in Stage 2
- Patients with any other prior malignancy are not allowed except for the following:
- Adequately treated basal cell or squamous cell skin cancer
- In situ cervical cancer
- Adequately treated Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 2 years
- Body mass index (BMI) <18.5 or >35 kg/m2.
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- On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities.
- Liver function tests documented within the screening period and on day -1 of treatment period:
- Total bilirubin > ULN (except in patients diagnosed with Gilbert's disease).
- Alkaline phosphatase > UNL or > 2.5 x UNL in case of liver metastases, or > 5 x UNL in case of bone metastases.
- ALT/AST > UNL or > 2.5 x UNL in case of liver metastases.
- Known positive virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B (surface antigen), or hepatitis C.
- Chronic inflammatory liver condition.
- Chronic adrenal failure or is receiving concurrent long-term corticosteroid therapy.
- 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.
- Used any prescription medication during the prior 1 month that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating.
- 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 systemic anticancer treatment (chemotherapy, targeted therapies including kinase inhibitors, antibodies, etc) less than 5 half-lives before the first dose of study drug or radiotherapy within 30 days; toxicity of the anticancer treatment must have recovered to grade 1 or less.
- Current progestin-based hormone replacement therapy.
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to swallow pills.
- Has a 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.
- Uncontrolled brain metastases or treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1.
- For Stage 2 only, mixed histology i.e. patients with >10% non-endometrioid malignant cells in provided histopathology samples.
Trial locations and contacts
3 sites in 1 country.
France3 sites, 3 recruiting
- Recruiting
Centre Oscar Lambret
Lille, 59020
Jacques Bonneterre, MD, [+33] (0)3.20.29.59.35, j-bonneterre@o-lambret.fr
- Recruiting
Institut Curie Oncologie Medicale
Paris, 75005
Paul H Cottu, MD, [+33] (0)14 4324000 ext. 4670, paul.cottu@curie.net
- Recruiting
Institut Gustave Roussy
Villejuif
Andrea Varga, MD, [+33] (0)1 42 11 42 96, andrea.varga@igr.fr
About this study
This is a multi-center, open-label, randomized, parallel group two-stage phase 1 study with a phase 2 expansion component in pts with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma. Stage 1: Six dose cohorts, 5 using the extended release tablet (ER) formulation (10 mg BID, 20 mg BID, 30 mg BID, 40 mg BID, 50 mg BID) and 1 using the immediate-release (IR) tablet formulation 100 mg QD will be randomized in parallel. After enrollment of 36 patients in Stage 1, a dose of 50 mg BID was determined to be the RP2D. Stage 2: An additional 10 patients with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma (Stage 2a) will be enrolled at the RP2D. Based on the response in Stage 2a, the cohort will be further expanded by up to 19 more patients to a total of 29 patients to confirm the efficacy and safety profile of onapristone in this selected patient population (Stage 2b).
- Conditions
- Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy
- Being tested
- onapristone
- Keywords
- endometrial cancer, ovarian cancer, breast cancer, uterine sarcoma, uterine endometrioid adenocarcinoma
- Medical subject headings
- Endometrial Neoplasms, Ovarian Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
onapristoneDrug
Also called ZK 98299
| Study group | Role | What they receive |
|---|---|---|
| onapristone 10 mg BID mg | 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 mg | Experimental | onapristone 40 mg BID mg extended-release tablets Receives: Drug: onapristone |
| onapristone 50 mg BID | Experimental | onapristone 50 mg BID extended-release tablets Receives: Drug: onapristone |
| onapristone 100 mg QD | Experimental | onapristone 100 mg QD immediate-release tablets Receives: Drug: onapristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: RP2D of a single agent extended-release tablet formulation of oral onapristone for future clinical development.
Measured: Baseline to 57 days post-first dose
Stage 2: ORR using RECIST 1.1 in 10-29 patients with recurrent or metastatic uterine endometrioid adenocarcinoma that is APRpos, and to determine the relationship between APR status and onapristone anti-tumor activity.
Measured: Baseline to 30 Days after last dose
Secondary outcomes (4)
Safety and tolerability of extended-release onapristone tablets BID and of immediate-release onapristone tablets QD
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values
Measured: Baseline to 30 Days after last dose
Comparison of safety of extended-release BID vs. immediate release QD schedules
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values
Measured: Baseline to 30 Days after last dose
Anti-tumor activity based on tumor assessments (RECIST 1.1) and dates of progression
Measured: Baseline to 30 Days after last dose
PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine
AUC, Cmax, Tmax, t1/2
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 posted31 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionOct 2015 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone TherapyStudies 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arno Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul H Cottu, MD, Principal investigator, Institut Curie, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02052128
- Sponsor's protocol ID
- ARN-AR18-CT-101
- Status last verified
- Jun 2015
- First submitted
- 28 Jan 2014
- Last updated
- 24 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cottu PH, Bonneterre J, Varga A, Campone M, Leary A, Floquet A, Berton-Rigaud D, Sablin MP, Lesoin A, Rezai K, Lokiec FM, Lhomme C, Bosq J, Bexon AS, Gilles EM, Proniuk S, Dieras V, Jackson DM, Zukiwski A, Italiano A. Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers. PLoS One. 2018 Oct 10;13(10):e0204973. doi: 10.1371/journal.pone.0204973. eCollection 2018.
PubMed 30304013
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
- Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers
- ClinicalTrials.gov ID
- NCT02052128
- Acronym / sponsor ID
- ARN-AR18-CT-101
- Conditions
- Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy
- Keywords
- endometrial cancer, ovarian cancer, breast cancer, uterine sarcoma, uterine endometrioid adenocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Arno TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 31 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 a multi-center, open-label, randomized, parallel group two-stage phase 1 study with a phase 2 expansion component in pts with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma. Stage 1: Six dose cohorts, 5 using the extended release tablet (ER) formulation (10 mg BID, 20 mg BID, 30 mg BID, 40 mg BID, 50 mg BID) and 1 using the immediate-release (IR) tablet formulation 100 mg QD will be randomized in parallel. After enrollment of 36 patients in Stage 1, a dose of 50 mg BID was determined to be the RP2D. Stage 2: An additional 10 patients with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma (Stage 2a) will be enrolled at the RP2D. Based on the response in Stage 2a, the cohort will be further expanded by up to 19 more patients to a total of 29 patients to confirm the efficacy and safety profile of onapristone in this selected patient population (Stage 2b).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| onapristone 10 mg BID mg | 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 mg | Experimental | Drug: onapristoneonapristone 40 mg BID mg extended-release tablets |
| onapristone 50 mg BID | Experimental | Drug: onapristoneonapristone 50 mg BID extended-release tablets |
| onapristone 100 mg QD | Experimental | Drug: onapristoneonapristone 100 mg QD immediate-release tablets |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Post- menopausal female patients, 18 years of age or greater.
- In Stage 1, recurrent or metastatic PR-expressing cancer that has the potential to benefit from an anti-progestin treatment including but not limited to endometrial cancer, ovarian, or breast cancer or uterine sarcoma. In Stage 2, recurrent or metastatic PR-expression uterine endometrioid adenocarcinoma that is determined to be APRpos.
- Patients who have metastatic or recurrent disease after previous surgery, radiation therapy, and/or chemotherapy are eligible. In Stage 1, no restriction is placed on the number of prior therapies. In Stage 2, patients may have 0 or 1 prior chemotherapy treatments for adjuvant or metastatic disease and no prior endocrine therapies.
- In Stage 1, evaluable disease per RECIST 1.1. In Stage 2, measurable disease.
- Appropriate archival OR current tissue blocks or biopsy specimens to determine ER/PR and APR status.
Key exclusion criteria (24 listed)
- Calculated creatinine clearance of <60 mL/min in Stage 1 and <40 mL/min in Stage 2
- Patients with any other prior malignancy are not allowed except for the following:
- Body mass index (BMI) <18.5 or >35 kg/m2.
- On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities.
- Liver function tests documented within the screening period and on day -1 of treatment period:
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 | onapristone 10 mg BID mg, onapristone 100 mg QD, onapristone 20 mg BID, onapristone 30 mg BID, onapristone 40 mg BID mg, onapristone 50 mg BID |
Primary outcome
Stage 1: RP2D of a single agent extended-release tablet formulation of oral onapristone for future clinical development.
Time frame: Baseline to 57 days post-first dose
Stage 2: ORR using RECIST 1.1 in 10-29 patients with recurrent or metastatic uterine endometrioid adenocarcinoma that is APRpos, and to determine the relationship between APR status and onapristone anti-tumor activity.
Time frame: Baseline to 30 Days after last dose
4 secondary outcomes
Safety and tolerability of extended-release onapristone tablets BID and of immediate-release onapristone tablets QD
Time frame: Baseline to 30 Days after last dose
Comparison of safety of extended-release BID vs. immediate release QD schedules
Time frame: Baseline to 30 Days after last dose
Anti-tumor activity based on tumor assessments (RECIST 1.1) and dates of progression
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.
- Derived from this study: PubMed 30304013Cottu PH, Bonneterre J, Varga A, Campone M, Leary A, Floquet A, Berton-Rigaud D, Sablin MP, Lesoin A, Rezai K, Lokiec FM, Lhomme C, Bosq J, Bexon AS, Gilles EM, Proniuk S, Dieras V, Jackson DM, Zukiwski A, Italiano A. Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers. PLoS One. 2018 Oct 10;13(10):e0204973. doi: 10.1371/journal.pone.0204973. eCollection 2018.
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.
Paul H Cottu, MD principal investigator
Institut Curie, Paris, France
3 sites 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 in people with Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy, run by Arno Therapeutics at 3 sites in France.
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 8 inclusion and 24 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 3 sites in France. 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?
Stage 1: RP2D of a single agent extended-release tablet formulation of oral onapristone for future clinical development. (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?
On the ClinicalTrials.gov record for NCT02052128, which also lists 1 linked publication.
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.