An Open-label Study of the Effect of Tomivosertib (eFT508) in Patients With Advanced Castrate-resistant Prostate Cancer

NCT03690141 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: eFT508-0009
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 10

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)

Conditions

Castrate-resistant Prostate Cancer (CRPC)

Keywords

Prostate Cancer; Castrate-resistant Prostate Cancer; CRPC; eFT508; eFT508-0009; tomivosertib

Outcome Measures

Primary Outcomes (1)

• Anti-tumor Response as Defined by a Patient Achieving Either of the Following Outcomes:

  * A ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4 weeks * Objective response according to iRECIST 1.1

  52 weeks

Secondary Outcomes (1)

• PSA Progression-free Survival From Start of Study Therapy Until the Date PSA Progression is First Observed.

  52 weeks

Study Arms (1)

tomivosertib (eFT508)

EXPERIMENTAL

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: eFT508

Interventions

eFT508 DRUG

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.

Also known as: tomivosertib

tomivosertib (eFT508)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Effector Therapeutics: lead

Study Sites (10)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Kimmel Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

The Urology Group

Cincinnati, Ohio, 45212, United States

Location

Lancaster Urology

Lancaster, Pennsylvania, 17604, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

University of Washington

Seattle, Washington, 89109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

tomivosertib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Mark Densel, Vice President Development Operations
• Organization: Effector Therapeutics

mdensel@effector.com

8589258215

Study Officials

• Lyon Gliech, MD

  Medpace, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: October 1, 2018
• Study Start: November 27, 2018
• Primary Completion: April 27, 2020
• Study Completion: April 27, 2020
• Last Updated: June 21, 2024
• Results First Posted: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)