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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02605083
Recruitment Status : Recruiting
First Posted : November 16, 2015
Last Update Posted : June 27, 2017
Information provided by (Responsible Party):
Effector Therapeutics

Brief 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.

Condition or disease Intervention/treatment Phase
Cancer Drug: eFT508 Phase 1 Phase 2

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2 Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
Study Start Date : November 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: eFT508
Escalation cohort
Drug: eFT508
Will be given orally once or twice daily. Each treatment cycle = 21 days.

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD)/Recommended dose (RD) [ Time Frame: Up to one year ]
  2. Overall response rate (ORR) [ Time Frame: Up to three years ]

Secondary Outcome Measures :
  1. Safety (Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)) [ Time Frame: Up to three year ]
    Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)

  2. Plasma concentration of eFT508 as characterized by maximum serum concentration (Cmax) [ Time Frame: Different time points up to 336 hours ]
  3. Plasma concentration of eFT508 as characterized by Area Under the Curve (AUC) [ Time Frame: Different time points up to 336 hours ]
  4. Changes in eIF4E phosphorylation in peripheral blood cells (PBMCs) [ Time Frame: Up to Day 14 ]
  5. Tumor control evaluated by modified RECIST criteria v 1.1 [ Time Frame: Up to three years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT02605083

Contact: Cara Casseday 858-925-8215
Contact: Debra Thoma Vallner, PhD, MBA 650-619-0015

United States, Colorado
SCRI at HealthONE Recruiting
Denver, Colorado, United States, 80218
Contact: Kelly Mozzetta    720-754-4646      
Principal Investigator: Gerald Falchook, MD         
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Anita Kunwar    239-349-8689      
Principal Investigator: Manish Patel, MD         
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Haleigh Nelson, MPH    615-329-7440      
Principal Investigator: Howard Burris, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Krystle Luna    713-563-2690      
Principal Investigator: Funda Meric-Bernstam, M.D.         
Sponsors and Collaborators
Effector Therapeutics
Study Director: Jeremy Barton, MD Effector Therapeutics

Responsible Party: Effector Therapeutics Identifier: NCT02605083     History of Changes
Other Study ID Numbers: eFT508-0001
First Posted: November 16, 2015    Key Record Dates
Last Update Posted: June 27, 2017
Last Verified: June 2017

Keywords provided by Effector Therapeutics:
Solid Tumor
Head and Neck