Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers

June 22, 2015 updated by: Arno Therapeutics
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 Overview

Status

Status

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

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.

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.
Interventional

Enrollment (Anticipated)

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.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Lille, France, 59020
        • Recruiting
        • Centre Oscar Lambret
        • Contact:
      • Paris, France, 75005
        • Recruiting
        • Institut Curie Oncologie Medicale
        • Contact:
      • Villejuif, France
        • Recruiting
        • Institut Gustave Roussy
        • Contact:

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

Female

Description

Inclusion Criteria:

  1. Post- menopausal female patients, 18 years of age or greater.
  2. 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.
  3. 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.
  4. In Stage 1, evaluable disease per RECIST 1.1. In Stage 2, measurable disease.
  5. Appropriate archival OR current tissue blocks or biopsy specimens to determine ER/PR and APR status.
  6. 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.
  7. ECOG performance status 0-1.
  8. Health care coverage.

Exclusion Criteria:

  1. Calculated creatinine clearance of <60 mL/min in Stage 1 and <40 mL/min in Stage 2

  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
  3. Body mass index (BMI) <18.5 or >35 kg/m2.
  4. On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities.

  5. 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.
  6. Known positive virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B (surface antigen), or hepatitis C.
  7. Chronic inflammatory liver condition.
  8. Chronic adrenal failure or is receiving concurrent long-term corticosteroid therapy.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Current progestin-based hormone replacement therapy.
  14. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to swallow pills.
  15. Has a mental incapacity or language barriers precluding adequate understanding, co-operation, and compliance with the study requirements.
  16. Is, in the judgment of the investigator, unable or unwilling to comply with the requirements of the study.
  17. Uncontrolled brain metastases or treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1.
  18. For Stage 2 only, mixed histology i.e. patients with >10% non-endometrioid malignant cells in provided histopathology samples.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
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.
Experimental: onapristone 20 mg BID
onapristone 20 mg BID extended-release tablets
Drug: onapristone
Other Names:
  • ZK 98299
Experimental: onapristone 30 mg BID
onapristone 30 mg BID extended-release tablets
Drug: onapristone
Other Names:
  • ZK 98299
Experimental: onapristone 10 mg BID mg
onapristone 10 mg BID extended-release tablets
Drug: onapristone
Other Names:
  • ZK 98299
Experimental: onapristone 40 mg BID mg
onapristone 40 mg BID mg extended-release tablets
Drug: onapristone
Other Names:
  • ZK 98299
Experimental: onapristone 50 mg BID
onapristone 50 mg BID extended-release tablets
Drug: onapristone
Other Names:
  • ZK 98299
Experimental: onapristone 100 mg QD
onapristone 100 mg QD immediate-release tablets
Drug: onapristone
Other Names:
  • ZK 98299

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
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
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
Baseline to 30 Days after last dose

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
Measure Description
Time Frame
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
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values
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
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values
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
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
AUC, Cmax, Tmax, t1/2
Baseline to 30 Days after last dose

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.
Arno Therapeutics

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.
  • Principal Investigator: Paul H Cottu, MD, Institut Curie, Paris, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
January 1, 2014

Primary Completion (Anticipated)

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.
October 1, 2015

Study Completion (Anticipated)

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.
April 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).
January 28, 2014

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.
January 29, 2014

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.
January 31, 2014

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.
June 24, 2015

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.
June 22, 2015

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.
June 1, 2015

More Information

Terms related to this study

Keywords

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.
  • ARN-AR18-CT-101

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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