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An Open-label 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 : Completed
First Posted : October 1, 2018
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Effector Therapeutics

Tracking Information
First Submitted Date  ICMJE September 10, 2018
First Posted Date  ICMJE October 1, 2018
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE October 12, 2018
Actual Primary Completion Date April 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2019)
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 iRECIST 1.1
Original Primary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-label Study Examining the Effect of Tomivosertib (eFT508) in Patients With Advanced Castrate-resistant Prostate Cancer (CRPC)
Official Title  ICMJE A Phase 2 Non-randomized Open-label Study Examining the Effect of Tomivosertib (eFT508) in Patients With Advanced Castrate-resistant Prostate Cancer (CRPC)
Brief Summary

This Phase 2 Open-label Study examines the efficacy, safety, tolerability, and pharmacokinetics (PK) of tomivosertib (eFT508) in Patients with advanced CRPC.

An Open-label Study Examining the Effect of tomivosertib (eFT508) in Patients with Advanced Castrate-resistant Prostate Cancer (CRPC)

Detailed Description This Phase 2 study examines the efficacy, safety, tolerability, and pharmacokinetics (PK) of tomivosertib (eFT508) in advanced CRPC patients who have documented PSA progression on treatment with apalutamide and/or abiraterone and/or enzalutamide and for whom no suitable curative therapy exists.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE Castrate-resistant Prostate Cancer (CRPC)
Intervention  ICMJE Drug: tomivosertib (eFT508)
This Phase 2 study examines the efficacy, safety, tolerability, and PK of tomivosertib (eFT508) in advanced CRPC patients who have documented PSA progression on treatment with apalutamide and/or abiraterone and/or enzalutamide and for whom no suitable curative therapy exists.
Study Arms  ICMJE 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.
Intervention: Drug: tomivosertib (eFT508)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 16, 2019)
16
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2018)
30
Actual Study Completion Date  ICMJE April 27, 2020
Actual Primary Completion Date April 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 and/or enzalutamide and/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 iRECIST/RECIST 1.1
    • Bone disease
  • Patients receiving bisphosphonate/receptor activator of nuclear factor kappa-Β ligand (RANKL) therapy must have been on stable doses for ≥ 4 weeks before the start of study therapy.
  • Completion of all previous therapy for the treatment of cancer ≥4 weeks before the start of study therapy.
  • 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 ≤3 x ULN)
  • Adequate renal function:

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

  • For male patients 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 patient 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; 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 patients with known or suspected central nervous system malignancy.
  • Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism within 6 months before the start of study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; unstable angina; 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 QTcF ≥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, before the start of study therapy.
  • 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 before the start of study therapy and evidence of withdrawal response.
  • Bicalutamide or nilutamide within 6 weeks before the start of study therapy and evidence of withdrawal response.
  • Enzalutamide or abiraterone or apalutamid within 4 weeks before the start of study therapy.

    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:

    1. intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection);
    2. Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent;
    3. Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
  • Use of a potent inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 7 days before 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 patient's ability to sign informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03690141
Other Study ID Numbers  ICMJE eFT508-0009
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Effector Therapeutics
Study Sponsor  ICMJE Effector Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Lyon Gliech, MD Medpace, Inc.
PRS Account Effector Therapeutics
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP