Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers
1 other identifier
interventional
60
1 country
3
Brief 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. 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2014
Typical duration for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2014
CompletedFirst Submitted
Initial submission to the registry
January 28, 2014
CompletedFirst Posted
Study publicly available on registry
January 31, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedJune 24, 2015
June 1, 2015
1.7 years
January 28, 2014
June 22, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Stage 1: RP2D of a single agent extended-release tablet formulation of oral onapristone for future clinical development.
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.
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
Baseline to 30 Days after last dose
Comparison of safety of extended-release BID vs. immediate release QD schedules
Baseline to 30 Days after last dose
Anti-tumor activity based on tumor assessments (RECIST 1.1) and dates of progression
Baseline to 30 Days after last dose
PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine
Baseline to 30 Days after last dose
Study Arms (6)
onapristone 10 mg BID mg
EXPERIMENTALonapristone 10 mg BID extended-release tablets
onapristone 20 mg BID
EXPERIMENTALonapristone 20 mg BID extended-release tablets
onapristone 30 mg BID
EXPERIMENTALonapristone 30 mg BID extended-release tablets
onapristone 40 mg BID mg
EXPERIMENTALonapristone 40 mg BID mg extended-release tablets
onapristone 50 mg BID
EXPERIMENTALonapristone 50 mg BID extended-release tablets
onapristone 100 mg QD
EXPERIMENTALonapristone 100 mg QD immediate-release tablets
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
Centre Oscar Lambret
Lille, 59020, France
Institut Curie Oncologie Medicale
Paris, 75005, France
Institut Gustave Roussy
Villejuif, France
Related Publications (1)
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.
PMID: 30304013DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Paul H Cottu, MD
Institut Curie, Paris, France
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2014
First Posted
January 31, 2014
Study Start
January 1, 2014
Primary Completion
October 1, 2015
Study Completion
April 1, 2016
Last Updated
June 24, 2015
Record last verified: 2015-06