Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Arno Therapeutics
Sponsor:
Information provided by (Responsible Party):
Arno Therapeutics
ClinicalTrials.gov Identifier:
NCT02049190
First received: January 28, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Metastatic Prostate Cancer
Androgen-independent Prostate Cancer
Recurrent Prostate Cancer
Drug: onapristone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Arno Therapeutics:

Primary Outcome Measures:
  • Dose limiting toxicities related to onapristone utilizing a day 57 safety cut off and based on CTCAE v4 [ Time Frame: Baseline to 57 days post-first dose ] [ Designated as safety issue: No ]
  • Response to onapristone [ Time Frame: Baseline to 30 Days after last dose ] [ Designated as safety issue: No ]
    • Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart
    • and / or
    • Conversion of circulating tumor cell count (CTC) from ≥5/7.5 ml blood to <5/7.5 ml blood nadir confirmed by at least two readings at least 4 weeks apart
    • and / or
    • PSA decline of ≥ 50% (according to the PCWG2).


Secondary Outcome Measures:
  • Safety and tolerability of extended-release onapristone tablets BID [ 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 changes in PSA and other clinical laboratory values.

  • 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 ]

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

  Eligibility

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

Inclusion Criteria:

  • Male patients, 18 years of age or greater;
  • Histologically confirmed adenocarcinoma of the prostate (without neuroendocrine differentiation or small cell features). For Stage 2 of the study, PR expression in ≥1% tumor cells;
  • Biopsy to determine current AR/PR and APR status
  • Metastatic or recurrent inoperable disease after previous surgery, radiation therapy, and/or chemotherapy;
  • No more than two prior chemotherapy regimens for CRPC (docetaxel rechallenge will be regarded as one line of chemotherapy);
  • Disease that has progressed by PSA on abiraterone or enzalutamide as the last line of treatment. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration);
  • 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 or Prostate Cancer Clinical Trials Working Group 2;
  • ECOG performance status 0-2;
  • Life expectancy ≥ 3 months;
  • Willing and able to sign written informed consent.

Exclusion Criteria:

  • 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;
  • 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 HIV, HBV or HCV
  • Chronic inflammatory liver condition. History or clinical evidence of any liver or biliary pathology;
  • 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;
  • 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 2 weeks 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 any of a number of specific anti-cancer therapies with known efficacy within predetermined timeframes prior to receipt of first dose of study drug, without withdrawal response and with no plans to initiate any of these during study;
  • 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, cooperation, and compliance with the study requirements;
  • Is, in the judgment of the investigator, unable or unwilling to comply with the requirements of the study.
  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: NCT02049190

Contacts
Contact: Joseph Bisaha 1-862-703-7170 jb@arnothera.com

Locations
United Kingdom
Inst of Cancer Research & Royal Marsden NHS Foundation Trust Not yet recruiting
Sutton Surrey, United Kingdom, SH2 5NG
Contact: Gerhardt Attard, MD, PhD, MRCP    (+44) 020 872224137    gerhardt.attard@icr.ac.uk   
Sub-Investigator: Johann S De Bono, MD, PhD, MSc, FRCP         
Sub-Investigator: Joaquin Mateo, MD         
Sponsors and Collaborators
Arno Therapeutics
  More Information

No publications provided

Responsible Party: Arno Therapeutics
ClinicalTrials.gov Identifier: NCT02049190     History of Changes
Other Study ID Numbers: ARN-AR18-CT-102
Study First Received: January 28, 2014
Last Updated: January 28, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Arno Therapeutics:
Advanced Prostate Cancer
Castration-resistant Prostate Cancer
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
onapristone

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Onapristone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 21, 2014