A Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors

Cancer Clinical Trial

Official title:

A Phase 1-2 Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02605083
• Other study ID #: eFT508-0001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 3, 2015
• Est. completion date: March 22, 2019

Study information

• Verified date: October 2020
• Source: Effector Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of eFT508.

Description:

eFT508 is an oral, potent and highly selective inhibitor of mitogen-activated protein kinase interacting kinase (MNK) 1 and 2. Dysregulated translation of messenger RNA (mRNA) plays a role in the pathogenesis of multiple solid tumors and hematological malignancies. MNK1 and MNK2 integrate signals from several oncogenic and immune signaling pathways (including RAS, p38 and Toll-like receptors) by phosphorylating eukaryotic initiation of factor 4E (eIF4E) and key effector proteins. Phosphorylation of these regulatory proteins by MNK1 and MNK2 selectively regulates the stability and translation of a subset of cellular mRNA that control tumor growth, the tumor microenvironment and immune signaling. Nonclinical studies indicate that eFT508 shows activity against various types of solid tumors. These nonclinical studies support initiation of clinical development of eFT508 in patients with cancer.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: March 22, 2019
• Est. primary completion date: January 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

2. Pathologically documented diagnosis of advanced solid tumor malignancy that progressed after appropriate prior therapy or has no potential for cure with currently available treatments.

3. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) outside of any prior radiation field.

4. At least 3 weeks post any treatments/therapies at the time of first dose.

5. Adequate bone marrow function.

6. Adequate hepatic function.

7. Adequate renal function.

8. Normal coagulation panel.

9. Negative antiviral serology.

10. Willingness to use effective contraception.

Exclusion Criteria:

1. Known central nervous system malignancy.

2. Gastrointestinal disease that may interfere with drug absorption.

3. Significant cardiovascular disease.

4. Significant ECG abnormalities.

5. Ongoing risk of bleeding due to active peptic ulcer disease, bleeding diathesis, or requirement for systemic anticoagulants. Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.

6. Ongoing systemic bacterial, fungal or viral infection (with the exception of fungal infections of the skin or nails).

7. Pregnancy or breastfeeding.

8. Major surgery within 4 weeks before the start of study therapy.

9. Prior solid organ or bone marrow progenitor cell transplantation.

10. Prior therapy with any known inhibitor of MNK1 or MNK2.

11. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids (can be using topical or inhaled corticosteroids).

12. Use of drugs that might pose a risk of a drug-drug interaction within 4-7 days before the start of study therapy.

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• eFT508
Will be given orally once or twice daily. Each treatment cycle = 21 days.

Locations

Country	Name	City	State
United States	SCRI at HealthONE	Denver	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Effector Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)/Recommended dose (RD)		Up to one year
Primary	Overall response rate (ORR)		Up to three years
Secondary	Safety (Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03))	Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)	Up to three year
Secondary	Plasma concentration of eFT508 as characterized by maximum serum concentration (Cmax)		Different time points up to 336 hours
Secondary	Plasma concentration of eFT508 as characterized by Area Under the Curve (AUC)		Different time points up to 336 hours
Secondary	Changes in eIF4E phosphorylation in peripheral blood cells (PBMCs)		Up to Day 14
Secondary	Tumor control evaluated by modified RECIST criteria v 1.1		Up to three years