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A Study Examining the Effect of Tomivosertib (eFT508) in Patients With Advanced Castrate-resistant Prostate Cancer (CRPC)

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ClinicalTrials.gov Identifier: NCT03690141
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : November 20, 2018
Sponsor:
Information provided by (Responsible Party):
Effector Therapeutics

Brief Summary:
This Phase 2 study examines the efficacy, safety, tolerability, and pharmacokinetics (PK) of tomivosertib (eFT508) in metastatic CRPC patients.

Condition or disease Intervention/treatment Phase
Castrate-resistant Prostate Cancer (CRPC) Drug: tomivosertib (eFT508) Phase 2

Detailed Description:
This Phase 2 study examines the efficacy, safety, tolerability, and pharmacokinetics (PK) of tomivosertib (eFT508) in metastatic CRPC patients who have documented PSA progression on treatment with abiraterone (A) or enzalutamide (E) and for whom no curative therapy exists.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: tomivosertib (eFT508) will be supplied as 100-mg capsules by the Sponsor. Capsules are packaged in 200-cc high-density polyethylene wide-mouth, round, white bottles, at either 100 or 150 units per bottle, induction sealed and capped with a 38-mm child-resistant closure.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Non-randomized Open-label Study Examining the Effect of Tomivosertib (eFT508) in Patients With Advanced Castrate-resistant Prostate Cancer (CRPC)
Actual Study Start Date : October 12, 2018
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: tomivosertib (eFT508)
Tomivosertib (eFT508) is a novel small-molecule, investigational drug being developed by eFFECTOR Therapeutics, Inc. as an anticancer therapy. Tomivosertib (eFT508) down regulates AR and acts by inhibiting mitogen-activated protein kinase-interacting serine/threonine kinase-1 (MNK1) and MNK2.
Drug: tomivosertib (eFT508)
This Phase 2 study examines the efficacy, safety, tolerability, and PK of tomivosertib (eFT508) in metastatic CRPC patients who have documented PSA progression on treatment with abiraterone (A) or enzalutamide (E) and for whom no curative therapy exists.




Primary Outcome Measures :
  1. Anti-tumor response as defined by a patient achieving either of the following outcomes: [ Time Frame: 52 weeks ]
    • A ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4 weeks
    • Objective response according to RECIST 1.1


Secondary Outcome Measures :
  1. PSA progression-free survival from start of study therapy until the date PSA progression is first observed. [ Time Frame: 52 weeks ]
    PSA progression is defined as a ≥25% increase in PSA from nadir or baseline (and by ≥2 ng/mL) and requires confirmation ≥3 weeks later.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men ≥18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Histologically or cytologically confirmed (by clinical site) adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
  • Ongoing androgen deprivation therapy with a GnRH analog or bilateral orchiectomy (surgical or medical castration).
  • Serum testosterone ≤1.73 nmol/L (50 ng/dL) at screening.
  • PSA progression on treatment with abiraterone or enzalutamide or apalutamide. PSA progression is defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each determination. PSA value at the screening visit should be ≥2 ng/mL. Patients may also have:

    • Soft tissue disease progression defined by RECIST 1.1
    • Bone disease progression defined by PCWG2 with 2 or more new lesions on bone scan.
  • Patients receiving bisphosphonate/receptor activator of nuclear factor kappa-Β ligand (RANKL) therapy must have been on stable doses for at least 4 weeks.
  • Completion of all previous therapy for the treatment of cancer ≥4 weeks before the start of study therapy.
  • Available tumor tissue (archival or fresh).
  • All acute toxic effects of any prior anti-tumor therapy resolved to Grade ≤1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], neurotoxicity [Grade 1 or 2 permitted], or bone marrow parameters [Grade 1 or 2 permitted with exceptions as noted below]).
  • Adequate bone marrow function:

    • Absolute neutrophil count (ANC) ≥1.0 x 109/L
    • Platelet count ≥75 x 109/L
    • Hemoglobin ≥80 g/L (8.0 g/dL or 4.9 mmol/L)
  • Adequate hepatic function:

    • Serum alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN), ≤ 5 x ULN in the presence of liver metastases
    • Serum aspartate aminotransferase (AST) ≤3 x ULN, ≤5 x ULN in presence of liver metastases
    • Serum bilirubin ≤1.5 x ULN (unless due to Gilbert's syndrome or hemolysis)
  • Adequate renal function:

    -Serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥30 mL/min using Cockcroft Gault equation (Appendix 13.4)

  • Normal coagulation profile:

    • Prothrombin time (PT) within the ULN
    • Activated partial thromboplastin time (aPTT) within the ULN
  • For male subjects who can father a child and are having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of study therapy and for ≥30 days following the last dose of study medication or to abstain from sexual intercourse for at least this period of time, and willingness to refrain from sperm donation from the start of study therapy to ≥90 days following the last dose of study drug.
  • Estimated life expectancy >12 weeks.
  • Willingness to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests and biopsies, other study procedures, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered.
  • Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects, potential risks and discomforts, and other pertinent aspects of study participation.

Exclusion Criteria:

  • History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥2 years.
  • Rapidly progressive, clinically unstable central nervous system malignancy. Note: Central nervous system imaging is only required in subjects with known or suspected central nervous system malignancy.
  • Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism within 6 months prior to start of study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg), or history of congenital prolonged QT syndrome.
  • Significant screening electrocardiogram (ECG) abnormalities, including unstable cardiac arrhythmia requiring medication, left bundle-branch block, 2nd-degree atrioventricular (AV) block type II, 3rd-degree AV block, Grade ≥2 bradycardia, or QTc 470 msec.
  • Symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable.
  • Patients with gastrointestinal disorders likely to interfere with absorption of study medication.
  • Major surgery within 4 weeks before the start of study therapy.
  • Prior treatment with chemotherapy within 3 weeks or at least 4 half-lives, whichever is longer.
  • Prior therapy with any known inhibitor of MNK-1 or MNK-2.
  • Treatment with 5-alpha reductase inhibitors within 4 weeks of enrollment.
  • Prior flutamide treatment within 4 weeks of Cycle 1 Day 1 and evidence of withdrawal response.
  • Bicalutamide or nilutamide within 6 weeks of Cycle 1 Day 1 and evidence of withdrawal response.
  • Enzalutamide or abiraterone within 4 weeks of Cycle 1 Day 1

    a. Steroids given in conjunction with abiraterone must be washed out for at least 2 weeks prior to Cycle 1 Day 1 unless the investigator chooses to maintain at a dose of ≤10 mg/day prednisone or equivalent.

  • Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto).
  • Current use of immunosuppressive medication at the time of randomization, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
  • Use of a potent inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 7 days prior to the start of study therapy or expected requirement for use of a CYP3A4 inhibitor or inducer during study therapy (Appendix 13.5).
  • Concurrent participation in another therapeutic clinical trial.
  • Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03690141


Contacts
Contact: Sarah Wheeler 858-925-8215 swheeler@effector.com

Locations
United States, Connecticut
Yale Cancer Center Not yet recruiting
New Haven, Connecticut, United States, 06510
Principal Investigator: Daniel Petrylak, M.D.         
United States, Illinois
Northwestern University Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Lela Lartey    312-695-1377    emanuela.lartey@northwestern.edu   
Principal Investigator: Maha Hussain, M.D.         
United States, Maryland
Kimmel Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21205
Contact: Rehab Abdallah    443-253-7021    rabdall1@jhmi.edu   
Principal Investigator: Michael Carducci, M.D.         
United States, Michigan
Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Elisabeth Heath, M.D.         
United States, Missouri
Washington University Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Andrew Atkocius    314-747-1343    a.atkocius@wustl.edu   
Principal Investigator: Joel Picus, M.D.         
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Principal Investigator: Nicholas Vogelzang, M.D.         
United States, Ohio
The Urology Group Recruiting
Cincinnati, Ohio, United States, 45212
Contact: Bill Corbett    513-841-7555    wcorbett@urologygroup.com   
Principal Investigator: Marc Pliskin, M.D.         
United States, Pennsylvania
Lancaster Urology Recruiting
Lancaster, Pennsylvania, United States, 17604
Contact: Dawn Stern    717-431-2285    Dawns@lancuro.com   
Principal Investigator: Paul Sieber, M.D.         
United States, South Carolina
Carolina Urologic Research Center Recruiting
Myrtle Beach, South Carolina, United States, 29572
Contact: Laura Prince    843-839-1679    lprince@curcmb.com   
Principal Investigator: Neal Shore, M.D.         
United States, Washington
University of Washington Not yet recruiting
Seattle, Washington, United States, 89109
Principal Investigator: Celestia Higano, M.D.         
Sponsors and Collaborators
Effector Therapeutics
Investigators
Study Director: Jeremy Barton, MD Effector Therapeutics

Responsible Party: Effector Therapeutics
ClinicalTrials.gov Identifier: NCT03690141     History of Changes
Other Study ID Numbers: eFT508-0009
First Posted: October 1, 2018    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Effector Therapeutics:
Prostate Cancer
Castrate-resistant Prostate Cancer
CRPC
Metastatic Prostate Cancer
Metastatic Castrate-resistant Prostate Cancer
eFT508
eFT508-0009
tomivosertib

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases