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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Arno Therapeutics
Sponsor:
Information provided by (Responsible Party):
Arno Therapeutics
ClinicalTrials.gov Identifier:
NCT02052128
First received: January 28, 2014
Last updated: June 22, 2015
Last verified: June 2015
  Purpose

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).


Condition Intervention Phase
Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy
Drug: onapristone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers

Resource links provided by NLM:


Further study details as provided by Arno Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values

  • Comparison of safety of extended-release BID vs. immediate release QD schedules [ Time Frame: Baseline to 30 Days after last dose ] [ Designated as safety issue: No ]
    Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values

  • Anti-tumor activity based on tumor assessments (RECIST 1.1) and dates of progression [ Time Frame: Baseline to 30 Days after last dose ] [ Designated as safety issue: No ]
  • PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine [ Time Frame: Baseline to 30 Days after last dose ] [ Designated as safety issue: No ]
    AUC, Cmax, Tmax, t1/2


Estimated Enrollment: 60
Study Start Date: January 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: onapristone 10 mg BID mg
onapristone 10 mg BID extended-release tablets
Drug: onapristone
Other Name: ZK 98299
Experimental: onapristone 20 mg BID
onapristone 20 mg BID extended-release tablets
Drug: onapristone
Other Name: ZK 98299
Experimental: onapristone 30 mg BID
onapristone 30 mg BID extended-release tablets
Drug: onapristone
Other Name: ZK 98299
Experimental: onapristone 40 mg BID mg
onapristone 40 mg BID mg extended-release tablets
Drug: onapristone
Other Name: ZK 98299
Experimental: onapristone 50 mg BID
onapristone 50 mg BID extended-release tablets
Drug: onapristone
Other Name: ZK 98299
Experimental: onapristone 100 mg QD
onapristone 100 mg QD immediate-release tablets
Drug: onapristone
Other Name: ZK 98299

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02052128

Contacts
Contact: Alice S Bexon, MD 1-617-417-7300 alice.bexon@bexonclinical.com

Locations
France
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Jacques Bonneterre, MD    [+33] (0)3.20.29.59.35    j-bonneterre@o-lambret.fr   
Institut Curie Oncologie Medicale Recruiting
Paris, France, 75005
Contact: Paul H Cottu, MD    [+33] (0)14 4324000 ext 4670    paul.cottu@curie.net   
Institut Gustave Roussy Recruiting
Villejuif, France
Contact: Andrea Varga, MD    [+33] (0)1 42 11 42 96    andrea.varga@igr.fr   
Sponsors and Collaborators
Arno Therapeutics
Investigators
Principal Investigator: Paul H Cottu, MD Institut Curie, Paris, France
  More Information

No publications provided

Responsible Party: Arno Therapeutics
ClinicalTrials.gov Identifier: NCT02052128     History of Changes
Other Study ID Numbers: ARN-AR18-CT-101
Study First Received: January 28, 2014
Last Updated: June 22, 2015
Health Authority: France: L'Agence nationale de sécurité du médicament et des produits de santé (ANSM)

Keywords provided by Arno Therapeutics:
endometrial cancer
ovarian cancer
breast cancer
uterine sarcoma
uterine endometrioid adenocarcinoma

Additional relevant MeSH terms:
Onapristone
Progesterone
Antineoplastic Agents
Fertility Agents
Fertility Agents, Female
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 03, 2015