Clinical trial NCT03690141: An Open-label Study of the Effect of Tomivosertib (eFT508) in Patients With Advanced Castrate-resistant Prostate Cancer
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Castrate-resistant Prostate Cancer (CRPC)
Keywords: Prostate Cancer
Castrate-resistant Prostate Cancer
CRPC
eFT508
eFT508-0009
tomivosertib
Lead sponsor: Effector Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-10-01
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Anti-tumor Response as Defined by a Patient Achieving Either of the Following Outcomes:
timeFrame: 52 weeks
Secondary outcomes:
measure: PSA Progression-free Survival From Start of Study Therapy Until the Date PSA Progression is First Observed.
timeFrame: 52 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Kimmel Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Lancaster
country: United States
facility: Lancaster Urology
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Medpace, Inc.
name: Lyon Gliech, MD
role: STUDY_DIRECTOR
References: